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Trial record 79 of 1120 for:    Oral Cancer | ( Map: Canada )

Oral HYCAMTIN Plus Whole Brain Radiation Therapy In Treatment Of Brain Metastases Resulting From Non-Small Lung Cancer

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ClinicalTrials.gov Identifier: NCT00390806
Recruitment Status : Completed
First Posted : October 20, 2006
Results First Posted : January 20, 2014
Last Update Posted : January 20, 2014
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Lung Cancer, Non-Small Cell
Interventions Drug: HYCAMTIN, oral capsules
Radiation: Radiation
Enrollment 472
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Chemoradiation: Topotecan Plus WBRT Radiation: WBRT Alone
Hide Arm/Group Description Participants received topotecan 1.1 milligrams per meters squared per day (mg/m2/day), orally followed approximately 2 hours later by whole-brain radiation therapy (WBRT) 3 Gray (Gy)/day to midline over the course of 10 days. After a 2-week washout period, participants completing chemoradiation and willing to participate in the Continuation Phase of the study received oral topotecan 2.3 mg/m2/day for 5 days, every 21 days, as monotherapy provided the baseline hematologic requirements were met. Monotherapy continued until disease progression or discontinuation. Chemoradiation participants choosing not to participate in the Continuation Phase may have received other chemotherapies or best supportive care, as determined by the investigator. Participants received WBRT 3 Gy/day for 10 days. Participants may have received other chemotherapies or best supportive care, as determined by the investigator.
Period Title: Overall Study
Started 236 236
Ongoing 4 2
Completed 206 204
Not Completed 30 32
Reason Not Completed
Lost to Follow-up             7             6
Protocol Violation             2             2
Withdrawal by Subject             12             15
Investigator Decision             4             6
Death             1             0
Physician Decision             0             1
Ongoing             4             2
Arm/Group Title Chemoradiation: Topotecan Plus WBRT Radiation: WBRT Alone Total
Hide Arm/Group Description Participants received topotecan 1.1 milligrams per meters squared per day (mg/m2/day), orally followed approximately 2 hours later by whole-brain radiation therapy (WBRT) 3 Gray (Gy)/day to midline over the course of 10 days. After a 2-week washout period, participants completing chemoradiation and willing to participate in the Continuation Phase of the study received oral topotecan 2.3 mg/m2/day for 5 days, every 21 days, as monotherapy provided the baseline hematologic requirements were met. Monotherapy continued until disease progression or discontinuation. Chemoradiation participants choosing not to participate in the Continuation Phase may have received other chemotherapies or best supportive care, as determined by the investigator. Participants received WBRT 3 Gy/day for 10 days. Participants may have received other chemotherapies or best supportive care, as determined by the investigator. Total of all reporting groups
Overall Number of Baseline Participants 236 236 472
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 236 participants 236 participants 472 participants
59.4  (8.56) 57.8  (8.65) 58.6  (8.63)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 236 participants 236 participants 472 participants
Female
84
  35.6%
78
  33.1%
162
  34.3%
Male
152
  64.4%
158
  66.9%
310
  65.7%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 236 participants 236 participants 472 participants
African American/African Heritage (Her.) 3 1 4
Central/South Asian Heritage 1 0 1
Japanese/East Asian Heritage/South East Asian Her. 0 3 3
Native Hawaiian or other Pacific Islander 1 0 1
White 230 232 462
Asian & White 1 0 1
1.Primary Outcome
Title Overall Survival
Hide Description Overall survival is defined as the time from randomization until the date of death due to any cause. The date of last contact was used for those participants who had not died or were lost to follow-up. These participants were classified as having been censored.
Time Frame From the time of Randomization until the date of death due to any cause (up to 195 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-Treat (ITT) Population: all randomized participants. Participants were analyzed by the treatment to which they were randomized, even if this differed from the treatment they actually received.
Arm/Group Title Chemoradiation: Topotecan Plus WBRT Radiation: WBRT Alone
Hide Arm/Group Description:
Participants received topotecan 1.1 milligrams per meters squared per day (mg/m2/day), orally followed approximately 2 hours later by whole-brain radiation therapy (WBRT) 3 Gray (Gy)/day to midline over the course of 10 days. After a 2-week washout period, participants completing chemoradiation and willing to participate in the Continuation Phase of the study received oral topotecan 2.3 mg/m2/day for 5 days, every 21 days, as monotherapy provided the baseline hematologic requirements were met. Monotherapy continued until disease progression or discontinuation. Chemoradiation participants choosing not to participate in the Continuation Phase may have received other chemotherapies or best supportive care, as determined by the investigator.
Participants received WBRT 3 Gy/day for 10 days. Participants may have received other chemotherapies or best supportive care, as determined by the investigator.
Overall Number of Participants Analyzed 236 236
Median (95% Confidence Interval)
Unit of Measure: months
4.0
(3.4 to 4.8)
3.6
(3.0 to 4.0)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Chemoradiation: Topotecan Plus WBRT, Radiation: WBRT Alone
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1862
Comments p-value from a stratified log-rank test is adjusted for Recursive Partitioning Analysis (RPA) class and the number of brain lesions at Screening.
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.88
Confidence Interval (2-Sided) 95%
0.73 to 1.07
Estimation Comments The hazard ratio is estimated using a Pike estimator. The hazard ratio from a stratified log-rank test is adjusted for RPA class and the number of brain lesions at Screening.
2.Secondary Outcome
Title Six-month Survival
Hide Description Six-month survival is defined as the percentage of participants alive at 6 months following randomization. The date of last contact was used for those participants who had not died or were lost to follow-up. These participants were classified as having been censored.
Time Frame Month 6
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population
Arm/Group Title Chemoradiation: Topotecan Plus WBRT Radiation: WBRT Alone
Hide Arm/Group Description:
Participants received topotecan 1.1 milligrams per meters squared per day (mg/m2/day), orally followed approximately 2 hours later by whole-brain radiation therapy (WBRT) 3 Gray (Gy)/day to midline over the course of 10 days. After a 2-week washout period, participants completing chemoradiation and willing to participate in the Continuation Phase of the study received oral topotecan 2.3 mg/m2/day for 5 days, every 21 days, as monotherapy provided the baseline hematologic requirements were met. Monotherapy continued until disease progression or discontinuation. Chemoradiation participants choosing not to participate in the Continuation Phase may have received other chemotherapies or best supportive care, as determined by the investigator.
Participants received WBRT 3 Gy/day for 10 days. Participants may have received other chemotherapies or best supportive care, as determined by the investigator.
Overall Number of Participants Analyzed 236 236
Measure Type: Number
Unit of Measure: percentage of participants
36 28
3.Secondary Outcome
Title Number of Participants With a Complete Response (CR) or a Partial Response (PR) (Central Nervous System [CNS]-Radiologic)
Hide Description The number of participants achieving either a CR or PR, per World Health Organization (WHO) Criteria, in the CNS was assessed. CR is defined as the complete disappearance of all known measurable (Must be accurately measured in >=1 dimension) and nonmeasurable disease, without clinical, laboratory, or radiological evidence of recurrence for at least 4 weeks. CR may have been defined in participants with measurable and/or non-measurable disease at Screening. PR is defined as at least a 50% decrease in the sum of the products of the greatest length and perpendicular width of all measurable disease with no clear increase in nonmeasurable disease in participants without measurable disease. In both cases, there must have been no appearance of new disease, and no clinical, laboratory, or radiological evidence of disease progression for at least 4 weeks. Assessment of response was performed by the investigator and was based on unconfirmed responses.
Time Frame From the time of Randomization until the time of CR or PR (up to 75 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population
Arm/Group Title Chemoradiation: Topotecan Plus WBRT Radiation: WBRT Alone
Hide Arm/Group Description:
Participants received topotecan 1.1 milligrams per meters squared per day (mg/m2/day), orally followed approximately 2 hours later by whole-brain radiation therapy (WBRT) 3 Gray (Gy)/day to midline over the course of 10 days. After a 2-week washout period, participants completing chemoradiation and willing to participate in the Continuation Phase of the study received oral topotecan 2.3 mg/m2/day for 5 days, every 21 days, as monotherapy provided the baseline hematologic requirements were met. Monotherapy continued until disease progression or discontinuation. Chemoradiation participants choosing not to participate in the Continuation Phase may have received other chemotherapies or best supportive care, as determined by the investigator.
Participants received WBRT 3 Gy/day for 10 days. Participants may have received other chemotherapies or best supportive care, as determined by the investigator.
Overall Number of Participants Analyzed 236 236
Measure Type: Number
Unit of Measure: participants
Complete response 23 11
Partial response 63 61
4.Secondary Outcome
Title Time to Response (TTR) (CNS-radiologic)
Hide Description TTR is defined as the time from Randomization until the first documented evidence of CR or PR in the CNS. CR is defined as the complete disappearance of all known measurable (Must be accurately measured in >=1 dimension) and nonmeasurable disease, without clinical, laboratory, or radiological evidence of recurrence for at least 4 weeks. CR may have been defined in participants with measurable and/or non-measurable disease at Screening. PR is defined as at least a 50% decrease in the sum of the products of the greatest length and perpendicular width of all measurable disease with no clear increase in nonmeasurable disease in participants without measurable disease. In both cases, there must have been no appearance of new disease, and no clinical, laboratory, or radiological evidence of disease progression for at least 4 weeks. Assessment of response was performed by the investigator and was based on unconfirmed responses.
Time Frame From the time of Randomization until the first documented evidence of CR or PR (up to 75 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Only those participants with a CR, PR, or a missing response were assessed. TTR was analyzed with censoring for extended loss to follow-up to account for two or more missed response assessments before a TTR event. The date of the last adequate CNS assessment before extended loss to follow-up was used for censored participants.
Arm/Group Title Chemoradiation: Topotecan Plus WBRT Radiation: WBRT Alone
Hide Arm/Group Description:
Participants received topotecan 1.1 milligrams per meters squared per day (mg/m2/day), orally followed approximately 2 hours later by whole-brain radiation therapy (WBRT) 3 Gray (Gy)/day to midline over the course of 10 days. After a 2-week washout period, participants completing chemoradiation and willing to participate in the Continuation Phase of the study received oral topotecan 2.3 mg/m2/day for 5 days, every 21 days, as monotherapy provided the baseline hematologic requirements were met. Monotherapy continued until disease progression or discontinuation. Chemoradiation participants choosing not to participate in the Continuation Phase may have received other chemotherapies or best supportive care, as determined by the investigator.
Participants received WBRT 3 Gy/day for 10 days. Participants may have received other chemotherapies or best supportive care, as determined by the investigator.
Overall Number of Participants Analyzed 173 170
Median (95% Confidence Interval)
Unit of Measure: weeks
8.0
(7.7 to 8.1)
8.1
(6.0 to 8.1)
5.Secondary Outcome
Title Time to Progression (TTP) (CNS-radiologic)
Hide Description TTP is defined as the time from Randomization until the first documented sign of disease progression in the CNS. Progressive disease (PD) is defined as an increase >=25% in any measurable lesion or, in participants with non-measurable disease only, an estimation of an increase >=25%. In both cases, determination of progression included the appearance of any new lesions, or signification worsening of conditions presumed to be related to malignancy. Participants with clinical or laboratory evidence of possible disease progression were to be evaluated radiologically. TTP was analyzed with censoring for extended loss to follow-up to account for two or more missed assessments before a TTP event. The date of the last adequate CNS assessment before extended loss to follow-up was used for censored participants.
Time Frame From the time of Randomization until the first documented sign of disease progression (up to 75 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population
Arm/Group Title Chemoradiation: Topotecan Plus WBRT Radiation: WBRT Alone
Hide Arm/Group Description:
Participants received topotecan 1.1 milligrams per meters squared per day (mg/m2/day), orally followed approximately 2 hours later by whole-brain radiation therapy (WBRT) 3 Gray (Gy)/day to midline over the course of 10 days. After a 2-week washout period, participants completing chemoradiation and willing to participate in the Continuation Phase of the study received oral topotecan 2.3 mg/m2/day for 5 days, every 21 days, as monotherapy provided the baseline hematologic requirements were met. Monotherapy continued until disease progression or discontinuation. Chemoradiation participants choosing not to participate in the Continuation Phase may have received other chemotherapies or best supportive care, as determined by the investigator.
Participants received WBRT 3 Gy/day for 10 days. Participants may have received other chemotherapies or best supportive care, as determined by the investigator.
Overall Number of Participants Analyzed 236 236
Median (95% Confidence Interval)
Unit of Measure: weeks
9.7
(8.1 to 13.9)
9.7
(8.3 to 10.9)
6.Secondary Outcome
Title Time to Progression (TTP) (All Sites of Disease-radiologic)
Hide Description TTP is defined as the time from Randomization until the first documented sign of disease progression in all sites of disease. Progressive disease (PD) is defined as an increase >=25% in any measurable lesion or, in participants with non-measurable disease only, an estimation of an increase >=25%. In both cases, determination of progression included the appearance of any new lesions, or signification worsening of conditions presumed to be related to malignancy. Participants with clinical or laboratory evidence of possible disease progression were to be evaluated radiologically. TTP was analyzed with censoring for extended loss to follow-up to account for two or more missed assessments before a TTP event. The date of the last adequate CNS assessment before extended loss to follow-up was used for censored participants.
Time Frame From the time of Randomization until the first documented sign of disease progression (up to 75 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population
Arm/Group Title Chemoradiation: Topotecan Plus WBRT Radiation: WBRT Alone
Hide Arm/Group Description:
Participants received topotecan 1.1 milligrams per meters squared per day (mg/m2/day), orally followed approximately 2 hours later by whole-brain radiation therapy (WBRT) 3 Gray (Gy)/day to midline over the course of 10 days. After a 2-week washout period, participants completing chemoradiation and willing to participate in the Continuation Phase of the study received oral topotecan 2.3 mg/m2/day for 5 days, every 21 days, as monotherapy provided the baseline hematologic requirements were met. Monotherapy continued until disease progression or discontinuation. Chemoradiation participants choosing not to participate in the Continuation Phase may have received other chemotherapies or best supportive care, as determined by the investigator.
Participants received WBRT 3 Gy/day for 10 days. Participants may have received other chemotherapies or best supportive care, as determined by the investigator.
Overall Number of Participants Analyzed 236 236
Median (95% Confidence Interval)
Unit of Measure: weeks
8.0
(6.7 to 8.7)
7.7
(6.1 to 8.1)
7.Secondary Outcome
Title Number of Participants Who Ranked Each Individual Indicated Neurological Sign and Symptom as None, Mild, Moderate, or Severe at Months 1 and 3
Hide Description Neurological signs and symptoms data were derived from a participant-reported diary. The participants were asked to assess the following signs and symptoms on a scale of none, mild, moderate, or severe at Months 1 and 3: headache, problems with balance/coordination (PB/C), leg weakness, arm weakness, loss of feeling/numbness (LofF/N), speech difficulty (SD), confusion, loss of memory (LofM), drowsiness, nausea, vomiting, dizziness, visual problems (VP), seizures, leg/ankle swelling (L/AS), heart burn, difficulty sleeping (DS), tiredness, and appetite/weight gain (A/WG).
Time Frame Months 1 and 3
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Only those participants who were assessed for the indicated sign and symptom at the indicated time point were analyzed.
Arm/Group Title Chemoradiation: Topotecan Plus WBRT Radiation: WBRT Alone
Hide Arm/Group Description:
Participants received topotecan 1.1 milligrams per meters squared per day (mg/m2/day), orally followed approximately 2 hours later by whole-brain radiation therapy (WBRT) 3 Gray (Gy)/day to midline over the course of 10 days. After a 2-week washout period, participants completing chemoradiation and willing to participate in the Continuation Phase of the study received oral topotecan 2.3 mg/m2/day for 5 days, every 21 days, as monotherapy provided the baseline hematologic requirements were met. Monotherapy continued until disease progression or discontinuation. Chemoradiation participants choosing not to participate in the Continuation Phase may have received other chemotherapies or best supportive care, as determined by the investigator.
Participants received WBRT 3 Gy/day for 10 days. Participants may have received other chemotherapies or best supportive care, as determined by the investigator.
Overall Number of Participants Analyzed 179 189
Measure Type: Number
Unit of Measure: participants
Headache, Month 1, none, n=179, 189 93 106
Headache, Month 1, mild, n=179, 189 71 68
Headache, Month 1, moderate, 179, 189 11 13
Headache, Month 1, severe, 179, 189 4 2
Headache, Month 3, none, n=109, 111 69 53
Headache, Month 3, mild, n=109, 111 33 41
Headache, Month 3, moderate, n=109, 111 5 14
Headache, Month 3, severe, n=109, 111 2 3
PB/C, Month 1, none, n=179, 188 84 79
PB/C, Month 1, mild, n=179, 188 66 71
PB/C, Month 1, moderate, n=179, 188 22 30
PB/C, Month 1, severe, n=179, 188 7 8
PB/C, Month 3, none, n=109, 111 69 46
PB/C, Month 3, mild, n=109, 111 28 36
PB/C, Month 3, moderate, n=109, 111 10 18
PB/C, Month 3, severe, n=109, 111 2 11
Leg weakness, Month 1, none, n=179, 188 47 59
Leg weakness, Month 1, mild, n=179, 188 73 72
Leg weakness, Month 1, moderate, n=179, 188 41 41
Leg weakness, Month 1, severe, n=179, 188 18 16
Leg weakness, Month 3, none, n=109, 111 28 34
Leg weakness, Month 3, mild, n=109, 111 51 37
Leg weakness, Month 3, moderate, n=109, 111 20 19
Leg weakness, Month 3, severe, n=109, 111 10 21
Arm weakness, Month 1, none, n=179, 188 96 97
Arm weakness, Month 1, mild, n=179, 188 55 60
Arm weakness, Month 1, moderate, n=179, 188 23 18
Arm weakness, Month 1, severe, n=179, 188 5 13
Arm weakness, Month 3, none, n=109, 111 60 53
Arm weakness, Month 3, mild, n=109, 111 39 34
Arm weakness, Month 3, molderate, n=109, 111 8 16
Arm weakness, Month 3, severe, n=109, 111 2 8
LofF/N, Month 1, none, n=179, 188 101 11
LofF/N, Month 1, mild, n=179, 188 53 43
LofF/N, Month 1, moderate, n=179, 188 17 25
LofF/N, Month 1, severe, n=179, 188 8 9
LofF/N, Month 3, none, n=109, 111 73 66
LofF/N, Month 3, mild, n=109, 111 28 27
LofF/N, Month 3, moderate, n=109, 111 3 11
LofF/N, Month 3, severe, n=109, 111 5 7
SD, Month 1, none, n=179, 188 151 137
SD, Month 1, mild, n=179, 188 16 40
SD, Month 1, moderate, n=179, 188 9 9
SD, Month 1, severe, n=179, 188 3 2
SD, Month 3, none, n=109, 110 94 78
SD, Month 3, mild, n=109, 110 11 22
SD, Month 3, moderate, n=109, 110 2 8
SD, Month 3, severe, n=109, 110 2 2
Confusion, Month 1, none, n=179, 188 150 148
Confusion, Month 1, mild, n=179, 188 20 32
Confusion, Month 1, moderate, n=179, 188 6 7
Confusion, Month 1, severe, n=179, 188 3 1
Confusion, Month 3, none, n=109, 110 99 71
Confusion, Month 3, mild, n=109, 110 7 29
Confusion, Month 3, moderate, n=109, 110 2 9
Confusion, Month 3, severe, n=109, 110 1 1
LofM, Month 1, none, n=179, 188 149 141
LofM, Month 1, mild, n=179, 188 20 41
LofM, Month 1, moderate, n=179, 188 8 5
LofM, Month 1, severe, n=179, 188 2 1
LofM, Month 3, none, n=109, 110 93 78
LofM, Month 3, mild, n=109, 110 14 25
LofM, Month 3, moderate, n=109, 110 1 6
LofM, Month 3, severe, n=109, 110 1 1
Drowsiness, Month 1, none, n=179, 188 90 96
Drowsiness, Month 1, mild, n=179, 188 55 59
Drowsiness, Month 1, moderate, n=179, 188 25 26
Drowsiness, Month 1, severe, n=179, 188 9 7
Drowsiness, Month 3, none, n=109, 111 50 44
Drowsiness, Month 3, mild, n=109, 111 42 40
Drowsiness, Month 3, moderate, n=109, 111 15 15
Drowsiness, Month 3, severe, n=109, 111 2 12
Nausea, Month 1, none, n=179, 188 125 142
Nausea, Month 1, mild, n=179, 188 38 36
Nausea, Month 1, moderate, n=179, 188 12 10
Nausea, Month 1, severe, n=179, 188 4 0
Nausea, Month 3, none, n=109, 111 70 73
Nausea, Month 3, mild, n=109, 111 31 29
Nausea, Month 3, moderate, n=109, 111 7 6
Nausea, Month 3, severe, n=109, 111 1 3
Vomiting, Month 1, none, n=179, 188 153 164
Vomiting, Month 1, mild, n=179, 188 20 19
Vomiting, Month 1, moderate, n=179, 188 4 4
Vomiting, Month 1, severe, n=179, 188 2 1
Vomiting, Month 3, none, n=109, 111 89 91
Vomiting, Month 3, mild, n=109, 111 15 15
Vomiting, Month 3, moderate, n=109, 111 4 3
Vomiting, Month 3, severe=109, 111 1 2
Dizziness, Month 1, none, n=179, 188 96 94
Dizziness, Month 1, mild, n=179, 188 58 70
Dizziness, Month 1, moderate, n=179, 188 22 21
Dizziness, Month 1, severe, n=179, 188 3 3
Dizziness, Month 3, none, n=109, 111 64 54
Dizziness, Month 3, mild, n=109, 111 35 36
Dizziness, Month 3, moderate, n=109, 111 7 14
Dizziness, Month 3, severe, n=109, 111 3 7
VP, Month 1, none, n=179, 188 103 117
VP, Month 1, mild, n=179, 188 54 53
VP, Month 1, moderate, n=179, 188 17 16
VP, Month 1, severe, n=179, 188 5 2
VP, Month 3, none, n=109, 111 72 69
VP, Month 3, mild, n=109, 111 29 28
VP, Month 3, moderate, n=109, 111 7 10
VP, Month 3, severe, n=109, 111 1 4
Seizures, Month 1, none, n=179, 188 173 179
Seizures, Month 1, mild, n=179, 188 5 7
Seizures, Month 1, moderate, n=179, 188 1 2
Seizures, Month 1, severe, n=179, 188 0 0
Seizures, Month 3, none, n=109, 110 108 102
Seizures, Month 3, mild, n=109, 110 0 4
Seizures, Month 3, moderate, n=109, 110 1 3
Seizures, Month 3, severe, n=109, 110 0 1
L/AS, Month 1, none, n=179, 188 141 138
L/AS, Month 1, mild, n=179, 188 21 29
L/AS, Month 1, moderate, n=179, 188 12 15
L/AS, Month 1, severe, n=179, 188 5 6
L/AS, Month 3, none, n=109, 111 86 85
L/AS, Month 3, mild, n=109, 111 19 19
L/AS, Month 3, moderate, n=109, 111 3 6
L/AS, Month 3, severe, n=109, 111 1 1
Heartburn, Month 1, none, n=179, 188 142 151
Heartburn, Month 1, mild, n=179, 188 26 27
Heartburn, Month 1, moderate, n=179, 188 9 9
Heartburn, Month 1, severe, n=179, 188 2 1
Heartburn, Month 3, none, n=109, 111 87 86
Heartburn, Month 3, mild, n=109, 111 16 18
Heartburn, Month 3, moderate, n=109, 111 4 6
Heartburn, Month 3, severe, n=109, 111 2 1
DS, Month 1, none, n=179, 188 112 109
DS, Month 1, mild, n=179, 188 41 48
DS, Month 1, moderate, n=179, 188 15 24
DS, Month 1, severe, n=179, 188 11 7
DS, Month 3, none, n=109, 110 78 71
DS, Month 3, mild, n=109, 110 20 23
DS, Month 3, moderate, n=109, 110 8 12
DS, Month 3, severe, n=109, 110 3 4
Tiredness, Month 1, none, n=179, 188 42 42
Tiredness, Month 1, mild, n=179, 188 75 85
Tiredness, Month 1, moderate, n=179, 188 46 44
Tiredness, Month 1, severe, n=179, 188 16 17
Tiredness, Month 3, none, n=109, 111 28 21
Tiredness, Month 3, mild, n=109, 111 52 42
Tiredness, Month 3, moderate, n=109, 111 19 32
Tiredness, Month 3, severe, n=109, 111 10 16
A/WG, Month 1, none, n=179, 188 107 113
A/WG, Month 1, mild, n=179, 188 42 41
A/WG, Month 1, moderate, n=179, 188 19 29
A/WG, Month 1, severe, n=179, 188 11 5
A/WG, Month 3, none, n=108, 111 71 73
A/WG, Month 3, mild, n=108, 111 27 23
A/WG, Month 3, moderate, n=108, 111 4 11
A/WG, Month 3, severe, n=108, 111 6 4
8.Secondary Outcome
Title Number of Participants With the Indicated Investigator Assessment for the Neurological Sign and Symptom of Level of Consciousness at Baseline, Month 1, and Month 3
Hide Description The investigator assessed participants for the neurological sign and symptom of level of consciousness and assigned each participant to one of the following categories: normal; somnolence or sedation not interfering with function (not intefering); somnolence or sedation interfering with function, but not activities of daily living (ADLs) (interfering); obtundation or stupor, difficult to arouse, inteferring with ADLs (obtundation or stupor); coma.
Time Frame Baseline, Month 1, and Month 3
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Only those participants who were assessed at the indicated time point were analyzed. If no data are presented for a particular status at a particular time point, then no participants had that status at that time point.
Arm/Group Title Chemoradiation: Topotecan Plus WBRT Radiation: WBRT Alone
Hide Arm/Group Description:
Participants received topotecan 1.1 milligrams per meters squared per day (mg/m2/day), orally followed approximately 2 hours later by whole-brain radiation therapy (WBRT) 3 Gray (Gy)/day to midline over the course of 10 days. After a 2-week washout period, participants completing chemoradiation and willing to participate in the Continuation Phase of the study received oral topotecan 2.3 mg/m2/day for 5 days, every 21 days, as monotherapy provided the baseline hematologic requirements were met. Monotherapy continued until disease progression or discontinuation. Chemoradiation participants choosing not to participate in the Continuation Phase may have received other chemotherapies or best supportive care, as determined by the investigator.
Participants received WBRT 3 Gy/day for 10 days. Participants may have received other chemotherapies or best supportive care, as determined by the investigator.
Overall Number of Participants Analyzed 230 228
Measure Type: Number
Unit of Measure: participants
Baseline, normal, n=230, 228 219 216
Month 1, normal, n=178, 180 171 169
Month 3, normal, n=109, 107 102 92
Baseline, not interfering, n=230, 228 7 9
Month 1, not interfering, n=178, 180 5 7
Month 3, not interfering, n=109, 107 3 8
Baseline, interfering, n=230, 228 3 3
Month 1, interfering, n=178, 180 0 4
Month 3, interfering, n=109, 107 3 5
Baseline, obtundation and stupor, n=230, 228 1 0
Month 1, obtundation and stupor, n=178, 180 2 0
Month 3, obtundation and stupor, n=109, 107 1 2
9.Secondary Outcome
Title Number of Participants With the Indicated Investigator Assessment for the Neurological Sign and Symptom of Headache at Baseline, Month 1, and Month 3
Hide Description The investigator (per Common Terminology Criteria for Adverse Events [CTCAE], version 3.0) assessed participants for headache and assigned each participant to one of the following categories: absent, Grade (G) 1, G 2, G 3, G 4, and G 5. Grade refers to the severity of the AE. The CTCAE displays G 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: G 1: mild, asymptomatic or mild symptoms, clinical or diagnostic observations only, intervention not indicated; G 2: moderate, minimal, local or noninvasive intervention indicated, limiting age-appropriate instrumental ADL; G 3: severe or medically significant but not immediately life-threatening, hospitalization or prolongation of hospitalization indicated, disabling, limiting self care ADL; G 4: life-threatening consequences, urgent intervention indicated; G 5: death related to AE.
Time Frame Baseline, Month 1, and Month 3
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Only those participants who were assessed at the indicated time point were analyzed. If no data are presented for a particular grade at a particular time point, then no participants had an event of that grade at that time point.
Arm/Group Title Chemoradiation: Topotecan Plus WBRT Radiation: WBRT Alone
Hide Arm/Group Description:
Participants received topotecan 1.1 milligrams per meters squared per day (mg/m2/day), orally followed approximately 2 hours later by whole-brain radiation therapy (WBRT) 3 Gray (Gy)/day to midline over the course of 10 days. After a 2-week washout period, participants completing chemoradiation and willing to participate in the Continuation Phase of the study received oral topotecan 2.3 mg/m2/day for 5 days, every 21 days, as monotherapy provided the baseline hematologic requirements were met. Monotherapy continued until disease progression or discontinuation. Chemoradiation participants choosing not to participate in the Continuation Phase may have received other chemotherapies or best supportive care, as determined by the investigator.
Participants received WBRT 3 Gy/day for 10 days. Participants may have received other chemotherapies or best supportive care, as determined by the investigator.
Overall Number of Participants Analyzed 230 228
Measure Type: Number
Unit of Measure: participants
Baseline, absent, n=230, 228 141 146
Month 1, absent, n=178, 180 126 127
Month 3, absent, n=109, 107 85 74
Baseline, Grade 1, n=230, 228 62 55
Month 1, Grade 1, n=178, 180 43 38
Month 3, Grade 1, n=109, 107 17 23
Baseline, Grade 2, n=230, 228 25 23
Month 1, Grade 2, n=178, 180 9 14
Month 3, Grade 2, n=109, 107 7 10
Baseline, Grade 3, n=230, 228 2 4
Month 1, Grade 3, n=178, 180 0 1
10.Secondary Outcome
Title Number of Participants With the Indicated Investigator Assessment for the Neurological Sign and Symptom of Dizziness/Lightheadedness at Baseline, Month 1, and Month 3
Hide Description The investigator (per CTCAE, version 3.0) assessed participants for dizziness/lightheadedness and assigned each participant to one of the following categories: absent, G 1, G 2, G 3, G 4, and G 5. Grade refers to the severity of the AE. The CTCAE displays G 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: G 1: mild, asymptomatic or mild symptoms, clinical or diagnostic observations only, intervention not indicated; G 2: moderate, minimal, local or noninvasive intervention indicated, limiting age-appropriate instrumental ADL; G 3: severe or medically significant but not immediately life-threatening, hospitalization or prolongation of hospitalization indicated, disabling, limiting self care ADL; G 4: life-threatening consequences, urgent intervention indicated; G 5: death related to AE.
Time Frame Baseline, Month 1, and Month 3
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Only those participants who were assessed at the indicated time point were analyzed. If no data are presented for a particular grade at a particular time point, then no participants had an event of that grade at that time point.
Arm/Group Title Chemoradiation: Topotecan Plus WBRT Radiation: WBRT Alone
Hide Arm/Group Description:
Participants received topotecan 1.1 milligrams per meters squared per day (mg/m2/day), orally followed approximately 2 hours later by whole-brain radiation therapy (WBRT) 3 Gray (Gy)/day to midline over the course of 10 days. After a 2-week washout period, participants completing chemoradiation and willing to participate in the Continuation Phase of the study received oral topotecan 2.3 mg/m2/day for 5 days, every 21 days, as monotherapy provided the baseline hematologic requirements were met. Monotherapy continued until disease progression or discontinuation. Chemoradiation participants choosing not to participate in the Continuation Phase may have received other chemotherapies or best supportive care, as determined by the investigator.
Participants received WBRT 3 Gy/day for 10 days. Participants may have received other chemotherapies or best supportive care, as determined by the investigator.
Overall Number of Participants Analyzed 230 228
Measure Type: Number
Unit of Measure: participants
Baseline, absent, n=230, 228 160 151
Month 1, absent, n=178, 180 124 128
Month 3, absent, n=109, 107 76 76
Baseline, Grade 1, n=230, 228 45 47
Month 1, Grade 1, n=178, 180 44 36
Month 3, Grade 1, n=109, 107 21 20
Baseline, Grade 2, n=230, 228 21 26
Month 1, Grade 2, n=178, 180 7 14
Month 3, Grade 2, n=109, 107 9 9
Baseline, Grade 3, n=230, 228 4 4
Month 1, Grade 3, n=178, 180 3 2
Month 3, Grade 3, n=109, 107 3 2
11.Secondary Outcome
Title Number of Participants With the Indicated Investigator Assessment for the Neurological Sign and Symptom of Vertigo at Baseline, Month 1, and Month 3
Hide Description The investigator (per CTCAE, version 3.0) assessed participants for vertigo and assigned each participant to one of the following categories: absent, G 1, G 2, G 3, G 4, and G 5. Grade refers to the severity of the AE. The CTCAE displays G 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: G 1: mild, asymptomatic or mild symptoms, clinical or diagnostic observations only, intervention not indicated; G 2: moderate, minimal, local or noninvasive intervention indicated, limiting age-appropriate instrumental ADL; G 3: severe or medically significant but not immediately life-threatening, hospitalization or prolongation of hospitalization indicated, disabling, limiting self care ADL; G 4: life-threatening consequences, urgent intervention indicated; G 5: death related to AE.
Time Frame Baseline, Month 1, and Month 3
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Only those participants who were assessed at the indicated time point were analyzed. If no data are presented for a particular grade at a particular time point, then no participants had an event of that grade at that time point.
Arm/Group Title Chemoradiation: Topotecan Plus WBRT Radiation: WBRT Alone
Hide Arm/Group Description:
Participants received topotecan 1.1 milligrams per meters squared per day (mg/m2/day), orally followed approximately 2 hours later by whole-brain radiation therapy (WBRT) 3 Gray (Gy)/day to midline over the course of 10 days. After a 2-week washout period, participants completing chemoradiation and willing to participate in the Continuation Phase of the study received oral topotecan 2.3 mg/m2/day for 5 days, every 21 days, as monotherapy provided the baseline hematologic requirements were met. Monotherapy continued until disease progression or discontinuation. Chemoradiation participants choosing not to participate in the Continuation Phase may have received other chemotherapies or best supportive care, as determined by the investigator.
Participants received WBRT 3 Gy/day for 10 days. Participants may have received other chemotherapies or best supportive care, as determined by the investigator.
Overall Number of Participants Analyzed 230 228
Measure Type: Number
Unit of Measure: participants
Baseline, absent, n=230, 228 180 173
Month 1, absent, n=178, 180 148 150
Month 3, absent, n=109, 107 90 86
Baseline, Grade 1, n=230, 228 26 30
Month 1, Grade 1, n=178, 180 19 19
Month 3, Grade 1, n=109, 107 14 13
Baseline, Grade 2, n=230, 228 19 22
Month 1, Grade 2, n=178, 180 7 9
Month 3, Grade 2, n=109, 107 4 6
Baseline, Grade 3, n=230, 228 5 3
Month 1, Grade 3, n=178, 180 3 2
Month 3, Grade 3, n=109, 107 1 2
Month 1, Grade 4, n=178, 180 1 0
12.Secondary Outcome
Title Number of Participants With the Indicated Investigator Assessment for the Neurological Sign and Symptom of Nausea/Vomiting at Baseline, Month 1, and Month 3
Hide Description The investigator (per CTCAE, version 3.0) assessed participants for nausea/vomiting and assigned each participant to one of the following categories: absent, G 1, G 2, G 3, G 4, and G 5. Grade refers to the severity of the AE. The CTCAE displays G 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: G 1: mild, asymptomatic or mild symptoms, clinical or diagnostic observations only, intervention not indicated; G 2: moderate, minimal, local or noninvasive intervention indicated, limiting age-appropriate instrumental ADL; G 3: severe or medically significant but not immediately life-threatening, hospitalization or prolongation of hospitalization indicated, disabling, limiting self care ADL; G 4: life-threatening consequences, urgent intervention indicated; G 5: death related to AE.
Time Frame Baseline, Month 1, and Month 3
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Only those participants who were assessed at the indicated time point were analyzed. If no data are presented for a particular grade at a particular time point, then no participants had an event of that grade at that time point.
Arm/Group Title Chemoradiation: Topotecan Plus WBRT Radiation: WBRT Alone
Hide Arm/Group Description:
Participants received topotecan 1.1 milligrams per meters squared per day (mg/m2/day), orally followed approximately 2 hours later by whole-brain radiation therapy (WBRT) 3 Gray (Gy)/day to midline over the course of 10 days. After a 2-week washout period, participants completing chemoradiation and willing to participate in the Continuation Phase of the study received oral topotecan 2.3 mg/m2/day for 5 days, every 21 days, as monotherapy provided the baseline hematologic requirements were met. Monotherapy continued until disease progression or discontinuation. Chemoradiation participants choosing not to participate in the Continuation Phase may have received other chemotherapies or best supportive care, as determined by the investigator.
Participants received WBRT 3 Gy/day for 10 days. Participants may have received other chemotherapies or best supportive care, as determined by the investigator.
Overall Number of Participants Analyzed 230 228
Measure Type: Number
Unit of Measure: participants
Baseline, absent, n=230, 228 203 192
Month 1, absent, n=178, 180 151 162
Month 3, absent, n=109, 107 88 93
Baseline, Grade 1, n=230, 228 19 22
Month 1, Grade 1, n=178, 180 20 15
Month 3, Grade 1, n=109, 107 14 11
Baseline, Grade 2, n=230, 228 7 10
Month 1, Grade 2, n=178, 180 6 3
Month 3, Grade 2, n=109, 107 6 3
Baseline, Grade 3, n=230, 228 1 4
Month 1, Grade 3, n=178, 180 1 0
Month 3, Grade 5, n=109, 107 1 0
13.Secondary Outcome
Title Number of Participants With the Indicated Investigator Assessment for the Neurological Sign and Symptom of Visual Problem at Baseline, Month 1, and Month 3
Hide Description The investigator (per CTCAE, version 3.0) assessed participants for visual problem and assigned each participant to one of the following categories: absent, G 1, G 2, G 3, G 4, and G 5. Grade refers to the severity of the AE. The CTCAE displays G 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: G 1: mild, asymptomatic or mild symptoms, clinical or diagnostic observations only, intervention not indicated; G 2: moderate, minimal, local or noninvasive intervention indicated, limiting age-appropriate instrumental ADL; G 3: severe or medically significant but not immediately life-threatening, hospitalization or prolongation of hospitalization indicated, disabling, limiting self care ADL; G 4: life-threatening consequences, urgent intervention indicated; G 5: death related to AE.
Time Frame Baseline, Month 1, and Month 3
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Only those participants who were assessed at the indicated time point were analyzed. If no data are presented for a particular grade at a particular time point, then no participants had an event of that grade at that time point.
Arm/Group Title Chemoradiation: Topotecan Plus WBRT Radiation: WBRT Alone
Hide Arm/Group Description:
Participants received topotecan 1.1 milligrams per meters squared per day (mg/m2/day), orally followed approximately 2 hours later by whole-brain radiation therapy (WBRT) 3 Gray (Gy)/day to midline over the course of 10 days. After a 2-week washout period, participants completing chemoradiation and willing to participate in the Continuation Phase of the study received oral topotecan 2.3 mg/m2/day for 5 days, every 21 days, as monotherapy provided the baseline hematologic requirements were met. Monotherapy continued until disease progression or discontinuation. Chemoradiation participants choosing not to participate in the Continuation Phase may have received other chemotherapies or best supportive care, as determined by the investigator.
Participants received WBRT 3 Gy/day for 10 days. Participants may have received other chemotherapies or best supportive care, as determined by the investigator.
Overall Number of Participants Analyzed 230 228
Measure Type: Number
Unit of Measure: participants
Baseline, absent, n=230, 228 181 189
Month 1, absent, n=178, 180 148 154
Month 3, absent, n=109, 107 93 93
Baseline, Grade 1, n=230, 228 22 25
Month 1, Grade 1, n=178, 180 16 19
Month 3, Grade 1, n=109, 107 12 10
Baseline, Grade 2, n=230, 228 20 13
Month 1, Grade 2, n=178, 180 11 6
Month 3, Grade 2, n=109, 107 4 3
Baseline, Grade 3, n=230, 228 5 1
Month 1, Grade 3, n=178, 180 2 1
Month 3, Grade 3, n=109, 107 0 1
Baseline, Grade 4, n=230, 228 2 0
Month 1, Grade 4, n=178, 180 1 0
14.Secondary Outcome
Title Number of Participants With the Indicated Investigator Assessment for the Neurological Sign and Symptom of Seizure at Baseline, Month 1, and Month 3
Hide Description The investigator (per CTCAE, version 3.0) assessed participants for seizure and assigned each participant to one of the following categories: absent, G 1, G 2, G 3, G 4, and G 5. Grade refers to the severity of the AE. The CTCAE displays G 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: G 1: mild, asymptomatic or mild symptoms, clinical or diagnostic observations only, intervention not indicated; G 2: moderate, minimal, local or noninvasive intervention indicated, limiting age-appropriate instrumental ADL; G 3: severe or medically significant but not immediately life-threatening, hospitalization or prolongation of hospitalization indicated, disabling, limiting self care ADL; G 4: life-threatening consequences, urgent intervention indicated; G 5: death related to AE.
Time Frame Baseline, Month 1, and Month 3
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Only those participants who were assessed at the indicated time point were analyzed. If no data are presented for a particular grade at a particular time point, then no participants had an event of that grade at that time point.
Arm/Group Title Chemoradiation: Topotecan Plus WBRT Radiation: WBRT Alone
Hide Arm/Group Description:
Participants received topotecan 1.1 milligrams per meters squared per day (mg/m2/day), orally followed approximately 2 hours later by whole-brain radiation therapy (WBRT) 3 Gray (Gy)/day to midline over the course of 10 days. After a 2-week washout period, participants completing chemoradiation and willing to participate in the Continuation Phase of the study received oral topotecan 2.3 mg/m2/day for 5 days, every 21 days, as monotherapy provided the baseline hematologic requirements were met. Monotherapy continued until disease progression or discontinuation. Chemoradiation participants choosing not to participate in the Continuation Phase may have received other chemotherapies or best supportive care, as determined by the investigator.
Participants received WBRT 3 Gy/day for 10 days. Participants may have received other chemotherapies or best supportive care, as determined by the investigator.
Overall Number of Participants Analyzed 230 228
Measure Type: Number
Unit of Measure: participants
Baseline, absent, n=230, 228 218 216
Month 1, absent, n=178, 180 175 178
Month 3, absent, n=109, 107 109 101
Baseline, Grade 1, n=230, 228 4 6
Month 1, Grade 1, n=178, 180 2 1
Month 3, Grade 1, n=109, 107 0 4
Baseline, Grade 2, n=230, 228 6 6
Month 1, Grade 2, n=178, 180 1 1
Month 3, Grade 2, n=109, 107 0 2
Baseline, Grade 3, n=230, 228 1 0
Baseline, Grade 4, n=230, 228 1 0
15.Secondary Outcome
Title Number of Participants With the Indicated Investigator Assessment for the Neurological Sign and Symptom of Other Neurological Symptoms at Baseline, Month 1, and Month 3
Hide Description The investigator (per CTCAE, version 3.0) assessed participants for other neurological symptoms and assigned each participant to one of the following categories: absent, G 1, G 2, G 3, G 4, and G 5. Grade refers to the severity of the AE. The CTCAE displays G 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: G 1: mild, asymptomatic or mild symptoms, clinical or diagnostic observations only, intervention not indicated; G 2: moderate, minimal, local or noninvasive intervention indicated, limiting age-appropriate instrumental ADL; G 3: severe or medically significant but not immediately life-threatening, hospitalization or prolongation of hospitalization indicated, disabling, limiting self care ADL; G 4: life-threatening consequences, urgent intervention indicated; G 5: death related to AE.
Time Frame Baseline, Month 1, and Month 3
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Only those participants who were assessed at the indicated time point were analyzed. If no data are presented for a particular grade at a particular time point, then no participants had an event of that grade at that time point.
Arm/Group Title Chemoradiation: Topotecan Plus WBRT Radiation: WBRT Alone
Hide Arm/Group Description:
Participants received topotecan 1.1 milligrams per meters squared per day (mg/m2/day), orally followed approximately 2 hours later by whole-brain radiation therapy (WBRT) 3 Gray (Gy)/day to midline over the course of 10 days. After a 2-week washout period, participants completing chemoradiation and willing to participate in the Continuation Phase of the study received oral topotecan 2.3 mg/m2/day for 5 days, every 21 days, as monotherapy provided the baseline hematologic requirements were met. Monotherapy continued until disease progression or discontinuation. Chemoradiation participants choosing not to participate in the Continuation Phase may have received other chemotherapies or best supportive care, as determined by the investigator.
Participants received WBRT 3 Gy/day for 10 days. Participants may have received other chemotherapies or best supportive care, as determined by the investigator.
Overall Number of Participants Analyzed 229 228
Measure Type: Number
Unit of Measure: participants
Baseline, absent, n=229, 228 219 214
Month 1, absent, n=177, 180 165 171
Month 3, absent, n=109, 107 99 101
Baseline, Grade 1, n=229, 228 2 5
Month 1, Grade 1, n=177, 180 2 6
Month 3, Grade 1, n=109, 107 6 5
Baseline, Grade 2, n=229, 228 7 8
Month 1, Grade 2, n=177, 180 8 1
Month 3, Grade 2, n=109, 107 3 1
Baseline, Grade 3, n=229, 228 1 1
Month 1, Grade 3, n=177, 180 2 1
Month 1, Grade 4, n=177, 180 0 1
Month 3, Grade 5, n=109, 107 1 0
16.Secondary Outcome
Title Number of Participants With the Indicated Investigator Assessment of Cranial Nerves II-XII at Baseline, Month 1, and Month 3
Hide Description The investigator assessed participants' status of cranial nerves II-XII and assigned each participant to one of the following categories: normal; present, not interfering with ADLs; present, interfering with ADLs; life threatening, disabling.
Time Frame Baseline, Month 1, and Month 3
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Only those participants who were assessed at the indicated time point were analyzed. If no data are presented for a particular status at a particular time point, then no participants had that status at that time point.
Arm/Group Title Chemoradiation: Topotecan Plus WBRT Radiation: WBRT Alone
Hide Arm/Group Description:
Participants received topotecan 1.1 milligrams per meters squared per day (mg/m2/day), orally followed approximately 2 hours later by whole-brain radiation therapy (WBRT) 3 Gray (Gy)/day to midline over the course of 10 days. After a 2-week washout period, participants completing chemoradiation and willing to participate in the Continuation Phase of the study received oral topotecan 2.3 mg/m2/day for 5 days, every 21 days, as monotherapy provided the baseline hematologic requirements were met. Monotherapy continued until disease progression or discontinuation. Chemoradiation participants choosing not to participate in the Continuation Phase may have received other chemotherapies or best supportive care, as determined by the investigator.
Participants received WBRT 3 Gy/day for 10 days. Participants may have received other chemotherapies or best supportive care, as determined by the investigator.
Overall Number of Participants Analyzed 229 225
Measure Type: Number
Unit of Measure: participants
Baseline, normal, n=229, 225 218 211
Month 1, normal, n=177, 179 172 169
Month 3, normal, n=109, 107 106 102
Baseline, present, not interfering, n=229, 225 11 10
Month 1, present, not interfering, n=177, 179 4 6
Month 3, present, not interfering, n=109, 107 3 2
Baseline, present, interfering, n=229, 225 0 4
Month 1, present, interfering, n=177, 179 1 4
Month 3, present, interfering, n=109, 107 0 3
17.Secondary Outcome
Title Number of Participants With the Indicated Investigator Assessment of Language (Dysphasia or Aphasia) at Baseline, Month 1, and Month 3
Hide Description The investigator assessed participants' status of language (dysphasia or aphasia) and assigned each participant to one of the following categories: absent; awareness of receptive or expressive aphasia, not impairing ability to communicate (not impaired); receptive or expressive dysphasia, impairing ability to communicate (impaired); inability to communicate (unable).
Time Frame Baseline, Month 1, and Month 3
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Only those participants who were assessed at the indicated time point were analyzed. If no data are presented for a particular status at a particular time point, then no participants had that status at that time point.
Arm/Group Title Chemoradiation: Topotecan Plus WBRT Radiation: WBRT Alone
Hide Arm/Group Description:
Participants received topotecan 1.1 milligrams per meters squared per day (mg/m2/day), orally followed approximately 2 hours later by whole-brain radiation therapy (WBRT) 3 Gray (Gy)/day to midline over the course of 10 days. After a 2-week washout period, participants completing chemoradiation and willing to participate in the Continuation Phase of the study received oral topotecan 2.3 mg/m2/day for 5 days, every 21 days, as monotherapy provided the baseline hematologic requirements were met. Monotherapy continued until disease progression or discontinuation. Chemoradiation participants choosing not to participate in the Continuation Phase may have received other chemotherapies or best supportive care, as determined by the investigator.
Participants received WBRT 3 Gy/day for 10 days. Participants may have received other chemotherapies or best supportive care, as determined by the investigator.
Overall Number of Participants Analyzed 230 228
Measure Type: Number
Unit of Measure: participants
Baseline, absent, n=230, 228 211 215
Month 1, absent, n=178, 180 169 173
Month 3, absent, n=109, 107 105 98
Baseline, not impaired, n=230, 228 15 10
Month 1, not impaired, n=178, 180 6 5
Month 3, not impaired, n=109, 107 3 7
Baseline, impaired, n=230, 228 3 3
Month 1, impaired, n=178, 180 3 2
Month 3, impaired, n=109, 107 1 0
Baseline, unable, n=230, 228 1 0
Month 3, unable, n=109, 107 0 2
18.Secondary Outcome
Title Number of Participants With the Indicated Investigator Assessment of Strength (Right Upper Extremity) at Baseline, Month 1, and Month 3
Hide Description The investigator assessed participants' status of strength (right upper extremity) and assigned each participant to one of the following categories: normal; Grade 1, asymptomatic with weakness on physical examination; Grade 2, symptomatic and interfering with function, but not interfering with ADLs; Grade 3, symptomatic and interfering with ADLs; Grade 4: bedridden or disabling.
Time Frame Baseline, Month 1, and Month 3
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Only those participants who were assessed at the indicated time point were analyzed. If no data are presented for a particular status at a particular time point, then no participants had that status at that time point.
Arm/Group Title Chemoradiation: Topotecan Plus WBRT Radiation: WBRT Alone
Hide Arm/Group Description:
Participants received topotecan 1.1 milligrams per meters squared per day (mg/m2/day), orally followed approximately 2 hours later by whole-brain radiation therapy (WBRT) 3 Gray (Gy)/day to midline over the course of 10 days. After a 2-week washout period, participants completing chemoradiation and willing to participate in the Continuation Phase of the study received oral topotecan 2.3 mg/m2/day for 5 days, every 21 days, as monotherapy provided the baseline hematologic requirements were met. Monotherapy continued until disease progression or discontinuation. Chemoradiation participants choosing not to participate in the Continuation Phase may have received other chemotherapies or best supportive care, as determined by the investigator.
Participants received WBRT 3 Gy/day for 10 days. Participants may have received other chemotherapies or best supportive care, as determined by the investigator.
Overall Number of Participants Analyzed 230 228
Measure Type: Number
Unit of Measure: participants
Baseline, normal, n=230, 228 203 195
Month 1, normal, n=178, 179 153 159
Month 3, normal, n=109, 107 93 89
Baseline, Grade 1, n=230, 228 15 16
Month 1, Grade 1, n=178, 179 13 12
Month 3, Grade 1, n=109, 107 10 10
Baseline, Grade 2, n=230, 228 6 12
Month 1, Grade 2, n=178, 179 6 5
Month 3, Grade 2, n=109, 107 4 5
Baseline, Grade 3, n=230, 228 5 5
Month 1, Grade 3, n=178, 179 4 2
Month 3, Grade 3, n=109, 107 2 3
Baseline, Grade 4, n=230, 228 1 0
Month 1, Grade 4, n=178, 179 2 1
19.Secondary Outcome
Title Number of Participants With the Indicated Investigator Assessment of Strength (Left Upper Extremity) at Baseline, Month 1, and Month 3
Hide Description The investigator assessed participants' status of strength (left upper extremity) and assigned each participant to one of the following categories: normal; Grade 1, asymptomatic with weakness on physical examination; Grade 2, symptomatic and interfering with function, but not interfering with ADLs; Grade 3, symptomatic and interfering with ADLs; Grade 4: bedridden or disabling.
Time Frame Baseline, Month 1, and Month 3
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Only those participants who were assessed at the indicated time point were analyzed. If no data are presented for a particular status at a particular time point, then no participants had that status at that time point.
Arm/Group Title Chemoradiation: Topotecan Plus WBRT Radiation: WBRT Alone
Hide Arm/Group Description:
Participants received topotecan 1.1 milligrams per meters squared per day (mg/m2/day), orally followed approximately 2 hours later by whole-brain radiation therapy (WBRT) 3 Gray (Gy)/day to midline over the course of 10 days. After a 2-week washout period, participants completing chemoradiation and willing to participate in the Continuation Phase of the study received oral topotecan 2.3 mg/m2/day for 5 days, every 21 days, as monotherapy provided the baseline hematologic requirements were met. Monotherapy continued until disease progression or discontinuation. Chemoradiation participants choosing not to participate in the Continuation Phase may have received other chemotherapies or best supportive care, as determined by the investigator.
Participants received WBRT 3 Gy/day for 10 days. Participants may have received other chemotherapies or best supportive care, as determined by the investigator.
Overall Number of Participants Analyzed 230 228
Measure Type: Number
Unit of Measure: participants
Baseline, normal, n=230, 228 197 202
Month 1, normal, n=178, 179 149 157
Month 3, normal, n=109, 107 90 86
Baseline, Grade 1, n=230, 228 16 13
Month 1, Grade 1, n=178, 179 16 13
Month 3, Grade 1, n=109, 107 10 11
Baseline, Grade 2, n=230, 228 11 8
Month 1, Grade 2, n=178, 179 8 5
Month 3, Grade 2, n=109, 107 6 5
Baseline, Grade 3, n=230, 228 6 4
Month 1, Grade 3, n=178, 179 3 2
Month 3, Grade 3, n=109, 107 3 4
Baseline, Grade 4, n=230, 228 0 1
Month 1, Grade 4, n=178, 179 2 2
Month 3, Grade 4, n=109, 107 0 1
20.Secondary Outcome
Title Number of Participants With the Indicated Investigator Assessment of Strength (Right Lower Extremity) at Baseline, Month 1, and Month 3
Hide Description The investigator assessed participants' status of strength (right lower extremity) and assigned each participant to one of the following categories: normal; Grade 1, asymptomatic with weakness on physical examination; Grade 2, symptomatic and interfering with function, but not interfering with ADLs; Grade 3, symptomatic and interfering with ADLs; Grade 4: bedridden or disabling.
Time Frame Baseline, Month 1, and Month 3
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Only those participants who were assessed at the indicated time point were analyzed. If no data are presented for a particular status at a particular time point, then no participants had that status at that time point.
Arm/Group Title Chemoradiation: Topotecan Plus WBRT Radiation: WBRT Alone
Hide Arm/Group Description:
Participants received topotecan 1.1 milligrams per meters squared per day (mg/m2/day), orally followed approximately 2 hours later by whole-brain radiation therapy (WBRT) 3 Gray (Gy)/day to midline over the course of 10 days. After a 2-week washout period, participants completing chemoradiation and willing to participate in the Continuation Phase of the study received oral topotecan 2.3 mg/m2/day for 5 days, every 21 days, as monotherapy provided the baseline hematologic requirements were met. Monotherapy continued until disease progression or discontinuation. Chemoradiation participants choosing not to participate in the Continuation Phase may have received other chemotherapies or best supportive care, as determined by the investigator.
Participants received WBRT 3 Gy/day for 10 days. Participants may have received other chemotherapies or best supportive care, as determined by the investigator.
Overall Number of Participants Analyzed 230 228
Measure Type: Number
Unit of Measure: participants
Baseline, normal, n=230, 228 196 189
Month 1, normal, n=178, 180 137 145
Month 3, normal, n=109, 107 81 80
Baseline, Grade 1, n=230, 228 20 19
Month 1, Grade 1, n=178, 180 17 15
Month 3, Grade 1, n=109, 107 12 11
Baseline, Grade 2, n=230, 228 9 16
Month 1, Grade 2, n=178, 180 11 19
Month 3, Grade 2, n=109, 107 11 11
Baseline, Grade 3, n=230, 228 3 4
Month 1, Grade 3, n=178, 180 9 0
Month 3, Grade 3, n=109, 107 4 3
Baseline, Grade 4, n=230, 228 2 0
Month 1, Grade 4, n=178, 180 4 1
Month 3, Grade 4, n=109, 107 1 2
21.Secondary Outcome
Title Number of Participants With the Indicated Investigator Assessment of Strength (Left Lower Extremity) at Baseline, Month 1, and Month 3
Hide Description The investigator assessed participants' status of strength (left lower extremity) and assigned each participant to one of the following categories: normal; Grade 1, asymptomatic with weakness on physical examination; Grade 2, symptomatic and interfering with function, but not interfering with ADLs; Grade 3, symptomatic and interfering with ADLs; Grade 4: bedridden or disabling.
Time Frame Baseline, Month 1, and Month 3
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Only those participants who were assessed at the indicated time point were analyzed. If no data are presented for a particular status at a particular time point, then no participants had that status at that time point.
Arm/Group Title Chemoradiation: Topotecan Plus WBRT Radiation: WBRT Alone
Hide Arm/Group Description:
Participants received topotecan 1.1 milligrams per meters squared per day (mg/m2/day), orally followed approximately 2 hours later by whole-brain radiation therapy (WBRT) 3 Gray (Gy)/day to midline over the course of 10 days. After a 2-week washout period, participants completing chemoradiation and willing to participate in the Continuation Phase of the study received oral topotecan 2.3 mg/m2/day for 5 days, every 21 days, as monotherapy provided the baseline hematologic requirements were met. Monotherapy continued until disease progression or discontinuation. Chemoradiation participants choosing not to participate in the Continuation Phase may have received other chemotherapies or best supportive care, as determined by the investigator.
Participants received WBRT 3 Gy/day for 10 days. Participants may have received other chemotherapies or best supportive care, as determined by the investigator.
Overall Number of Participants Analyzed 230 228
Measure Type: Number
Unit of Measure: participants
Baseline, normal, n=230, 228 182 190
Month 1, normal, n=178, 179 128 143
Month 3, normal, n=109, 107 76 73
Baseline, Grade 1, n=230, 228 28 18
Month 1, Grade 1, n=178, 179 26 13
Month 3, Grade 1, n=109, 107 11 11
Baseline, Grade 2, n=230, 228 15 15
Month 1, Grade 2, n=178, 179 11 17
Month 3, Grade 2, n=109, 107 14 14
Baseline, Grade 3, n=230, 228 4 3
Month 1, Grade 3, n=178, 179 10 4
Month 3, Grade 3, n=109, 107 6 5
Baseline, Grade 4, n=230, 228 1 2
Month 1, Grade 4, n=178, 179 3 2
Month 3, Grade 4, n=109, 107 2 4
22.Secondary Outcome
Title Number of Participants With the Indicated Investigator Assessment of Sensation at Baseline, Month 1, and Month 3
Hide Description The investigator assessed participants' status of sensation and assigned each participant to one of the following categories: normal; loss of deep tendon reflexes or paresthesia, but not interfering with function (not interfering with function); objective sensory loss or paresthesia interfering with function, but not interfering with ADLs (interfering with function); sensory loss or paresthesia interfering with ADLs (intefering with ADLs); permanent sensory loss that interferes with function (permanent sensory loss).
Time Frame Baseline, Month 1, and Month 3
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Only those participants who were assessed at the indicated time point were analyzed. If no data are presented for a particular status at a particular time point, then no participants had that status at that time point.
Arm/Group Title Chemoradiation: Topotecan Plus WBRT Radiation: WBRT Alone
Hide Arm/Group Description:
Participants received topotecan 1.1 milligrams per meters squared per day (mg/m2/day), orally followed approximately 2 hours later by whole-brain radiation therapy (WBRT) 3 Gray (Gy)/day to midline over the course of 10 days. After a 2-week washout period, participants completing chemoradiation and willing to participate in the Continuation Phase of the study received oral topotecan 2.3 mg/m2/day for 5 days, every 21 days, as monotherapy provided the baseline hematologic requirements were met. Monotherapy continued until disease progression or discontinuation. Chemoradiation participants choosing not to participate in the Continuation Phase may have received other chemotherapies or best supportive care, as determined by the investigator.
Participants received WBRT 3 Gy/day for 10 days. Participants may have received other chemotherapies or best supportive care, as determined by the investigator.
Overall Number of Participants Analyzed 230 228
Measure Type: Number
Unit of Measure: participants
Baseline (BL), normal, n=230, 228 197 192
Month (M) 1, normal, n=178, 180 144 159
Month 3, normal, n=109, 107 100 94
BL, not interfering with function, n=230, 228 26 26
M 1, not interfering with function, n=178, 180 22 15
M 3, not interfering with function, n=109, 107 5 9
BL, interfering with function, n=230, 228 3 6
M 1, interfering with function, n=178, 180 7 4
M 3, interfering with function, n=109, 107 2 2
Baseline, interfering with ADLs, n=230, 228 4 3
Month 1, interfering with ADLs, n=178, 180 5 2
Month 3, interfering with ADLs, n=109, 107 2 2
Baseline, permanent sensory loss, n=230, 228 0 1
23.Secondary Outcome
Title Number of Participants With the Indicated Investigator Assessment of Ataxia (Right Upper Extremity: Finger to Nose Testing) at Baseline, Month 1, and Month 3
Hide Description The investigator assessed participants' status of ataxia (right upper extremity: finger to nose testing) and assigned each participant to one of the following categories: normal; Grade 1, asymptomatic but abnormal on physical examination, and not interfering with function; Grade 2, mild symptoms interfering with function, but not interfering with ADLs; Grade 3, moderate symptoms interfering with ADLs; Grade 4, bedridden or disabling.
Time Frame Baseline, Month 1, and Month 3
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Only those participants who were assessed at the indicated time point were analyzed. If no data are presented for a particular status at a particular time point, then no participants had that status at that time point.
Arm/Group Title Chemoradiation: Topotecan Plus WBRT Radiation: WBRT Alone
Hide Arm/Group Description:
Participants received topotecan 1.1 milligrams per meters squared per day (mg/m2/day), orally followed approximately 2 hours later by whole-brain radiation therapy (WBRT) 3 Gray (Gy)/day to midline over the course of 10 days. After a 2-week washout period, participants completing chemoradiation and willing to participate in the Continuation Phase of the study received oral topotecan 2.3 mg/m2/day for 5 days, every 21 days, as monotherapy provided the baseline hematologic requirements were met. Monotherapy continued until disease progression or discontinuation. Chemoradiation participants choosing not to participate in the Continuation Phase may have received other chemotherapies or best supportive care, as determined by the investigator.
Participants received WBRT 3 Gy/day for 10 days. Participants may have received other chemotherapies or best supportive care, as determined by the investigator.
Overall Number of Participants Analyzed 229 228
Measure Type: Number
Unit of Measure: participants
Baseline, normal, n=229, 228 206 198
Month 1, normal, 178, 179 166 166
Month 3, normal, n=109, 107 103 95
Baseline, Grade 1, n=229, 228 13 17
Month 1, Grade 1, 178, 179 7 6
Month 3, Grade 1, n=109, 107 6 5
Baseline, Grade 2, n=229, 228 5 12
Month 1, Grade 2, 178, 179 3 6
Month 3, Grade 2, n=109, 107 0 5
Baseline, Grade 3, n=229, 228 3 1
Month 3, Grade 3, n=109, 107 0 1
Baseline, Grade 4, n=229, 228 2 0
Month 1, Grade 4, 178, 179 2 1
Month 3, Grade 4, n=109, 107 0 1
24.Secondary Outcome
Title Number of Participants With the Indicated Investigator Assessment of Ataxia (Left Upper Extremity: Finger to Nose Testing) at Baseline, Month 1, and Month 3
Hide Description The investigator assessed participants' status of ataxia (left upper extremity: finger to nose testing) and assigned each participant to one of the following categories: normal; Grade 1, asymptomatic but abnormal on physical examination, and not interfering with function; Grade 2, mild symptoms interfering with function, but not interfering with ADLs; Grade 3, moderate symptoms interfering with ADLs; Grade 4, bedridden or disabling.
Time Frame Baseline, Month 1, and Month 3
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Only those participants who were assessed at the indicated time point were analyzed. If no data are presented for a particular status at a particular time point, then no participants had that status at that time point.
Arm/Group Title Chemoradiation: Topotecan Plus WBRT Radiation: WBRT Alone
Hide Arm/Group Description:
Participants received topotecan 1.1 milligrams per meters squared per day (mg/m2/day), orally followed approximately 2 hours later by whole-brain radiation therapy (WBRT) 3 Gray (Gy)/day to midline over the course of 10 days. After a 2-week washout period, participants completing chemoradiation and willing to participate in the Continuation Phase of the study received oral topotecan 2.3 mg/m2/day for 5 days, every 21 days, as monotherapy provided the baseline hematologic requirements were met. Monotherapy continued until disease progression or discontinuation. Chemoradiation participants choosing not to participate in the Continuation Phase may have received other chemotherapies or best supportive care, as determined by the investigator.
Participants received WBRT 3 Gy/day for 10 days. Participants may have received other chemotherapies or best supportive care, as determined by the investigator.
Overall Number of Participants Analyzed 230 227
Measure Type: Number
Unit of Measure: participants
Baseline, normal, n=230, 227 199 201
Month 1, normal, n=178, 178 156 162
Month 3, normal, n=109, 107 97 94
Baseline, Grade 1, n=230, 227 15 13
Month 1, Grade 1, n=178, 178 14 9
Month 3, Grade 1, n=109, 107 10 6
Baseline, Grade 2, n=230, 227 8 7
Month 1, Grade 2, n=178, 178 6 3
Month 3, Grade 2, n=109, 107 2 3
Baseline, Grade 3, n=230, 227 8 4
Month 1, Grade 3, n=178, 178 0 3
Month 3, Grade 3, n=109, 107 0 1
Baseline, Grade 4, n=230, 227 0 2
Month 1, Grade 4, n=178, 178 2 1
Month 3, Grade 4, n=109, 107 0 3
25.Secondary Outcome
Title Number of Participants With the Indicated Investigator Assessment of Ataxia (Gait) at Baseline, Month 1, and Month 3
Hide Description The investigator assessed participants' status of ataxia (gait) and assigned each participant to one of the following categories: normal; Grade 1, asymptomatic but abnormal on physical examination, and not interfering with function; Grade 2, mild symptoms interfering with function, but not interfering with ADLs; Grade 3, moderate symptoms interfering with ADLs; Grade 4, bedridden or disabling.
Time Frame Baseline, Month 1, and Month 3
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Only those participants who were assessed at the indicated time point were analyzed. If no data are presented for a particular status at a particular time point, then no participants had that status at that time point.
Arm/Group Title Chemoradiation: Topotecan Plus WBRT Radiation: WBRT Alone
Hide Arm/Group Description:
Participants received topotecan 1.1 milligrams per meters squared per day (mg/m2/day), orally followed approximately 2 hours later by whole-brain radiation therapy (WBRT) 3 Gray (Gy)/day to midline over the course of 10 days. After a 2-week washout period, participants completing chemoradiation and willing to participate in the Continuation Phase of the study received oral topotecan 2.3 mg/m2/day for 5 days, every 21 days, as monotherapy provided the baseline hematologic requirements were met. Monotherapy continued until disease progression or discontinuation. Chemoradiation participants choosing not to participate in the Continuation Phase may have received other chemotherapies or best supportive care, as determined by the investigator.
Participants received WBRT 3 Gy/day for 10 days. Participants may have received other chemotherapies or best supportive care, as determined by the investigator.
Overall Number of Participants Analyzed 230 227
Measure Type: Number
Unit of Measure: participants
Baseline, normal, n=230, 227 172 178
Month 1, normal, n=178, 179 138 147
Month 3, normal, n=108, 107 85 76
Baseline, Grade 1, n=230, 227 13 22
Month 1, Grade 1, n=178, 179 16 13
Month 3, Grade 1, n=108, 107 9 10
Baseline, Grade 2, n=230, 227 37 20
Month 1, Grade 2, n=178, 179 14 14
Month 3, Grade 2, n=108, 107 9 12
Baseline, Grade 3, n=230, 227 6 6
Month 1, Grade 3, n=178, 179 7 3
Month 3, Grade 3, n=108, 107 4 5
Baseline, Grade 4, n=230, 227 2 1
Month 1, Grade 4, n=178, 179 3 2
Month 3, Grade 4, n=108, 107 1 4
26.Secondary Outcome
Title Number of Participants With the Indicated Investigator Assessment of Ataxia (Balance) at Baseline, Month 1, and Month 3
Hide Description The investigator assessed participants' status of ataxia (balance) and assigned each participant to one of the following categories: normal; Grade 1, asymptomatic but abnormal on physical examination, and not interfering with function; Grade 2, mild symptoms interfering with function, but not interfering with ADLs; Grade 3, moderate symptoms interfering with ADLs; Grade 4, bedridden or disabling.
Time Frame Baseline, Month 1, and Month 3
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Only those participants who were assessed at the indicated time point were analyzed. If no data are presented for a particular status at a particular time point, then no participants had that status at that time point.
Arm/Group Title Chemoradiation: Topotecan Plus WBRT Radiation: WBRT Alone
Hide Arm/Group Description:
Participants received topotecan 1.1 milligrams per meters squared per day (mg/m2/day), orally followed approximately 2 hours later by whole-brain radiation therapy (WBRT) 3 Gray (Gy)/day to midline over the course of 10 days. After a 2-week washout period, participants completing chemoradiation and willing to participate in the Continuation Phase of the study received oral topotecan 2.3 mg/m2/day for 5 days, every 21 days, as monotherapy provided the baseline hematologic requirements were met. Monotherapy continued until disease progression or discontinuation. Chemoradiation participants choosing not to participate in the Continuation Phase may have received other chemotherapies or best supportive care, as determined by the investigator.
Participants received WBRT 3 Gy/day for 10 days. Participants may have received other chemotherapies or best supportive care, as determined by the investigator.
Overall Number of Participants Analyzed 230 228
Measure Type: Number
Unit of Measure: participants
Baseline, normal, n=230, 228 153 152
Month 1, normal, n=178, 178 131 128
Month 3, normal, n=108, 107 78 75
Baseline, Grade 1, n=230, 228 37 44
Month 1, Grade 1, n=178, 178 23 28
Month 3, Grade 1, n=108, 107 17 13
Baseline, Grade 2, n=230, 228 27 23
Month 1, Grade 2, n=178, 178 13 16
Month 3, Grade 2, n=108, 107 8 9
Baseline, Grade 3, n=230, 228 10 7
Month 1, Grade 3, n=178, 178 8 5
Month 3, Grade 3, n=108, 107 4 5
Baseline, Grade 4, n=230, 228 3 2
Month 1, Grade 4, n=178, 178 3 1
Month 3, Grade 4, n=108, 107 1 5
27.Secondary Outcome
Title Number of Participants With Any Adverse Event (AE; Both Serious and Non-serious) or Serious Adverse Event (SAE)
Hide Description An AE is defined as any untoward medical occurrence in a patient or clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose: results in death; is life threatening; requires hospitalization or prolongation of existing hospitalization; results in disability/incapacity; is a congenital anomaly/birth defect. For a list of all SAEs and AEs, see the SAE/AE module of this results summary.
Time Frame From Randomization until the last clinic visit associated with the study, up until 35 days after the start of the last course of treatment (up to 75 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
Modified ITT Population: all randomized participants who received at least one dose of randomized therapy. Participants were analyzed by the actual treatment received, even if this differed from the treatment to which they were randomized.
Arm/Group Title Chemoradiation: Topotecan Plus WBRT Radiation: WBRT Alone
Hide Arm/Group Description:
Participants received topotecan 1.1 milligrams per meters squared per day (mg/m2/day), orally followed approximately 2 hours later by whole-brain radiation therapy (WBRT) 3 Gray (Gy)/day to midline over the course of 10 days. After a 2-week washout period, participants completing chemoradiation and willing to participate in the Continuation Phase of the study received oral topotecan 2.3 mg/m2/day for 5 days, every 21 days, as monotherapy provided the baseline hematologic requirements were met. Monotherapy continued until disease progression or discontinuation. Chemoradiation participants choosing not to participate in the Continuation Phase may have received other chemotherapies or best supportive care, as determined by the investigator.
Participants received WBRT 3 Gy/day for 10 days. Participants may have received other chemotherapies or best supportive care, as determined by the investigator.
Overall Number of Participants Analyzed 235 233
Measure Type: Number
Unit of Measure: participants
AE 204 148
SAE 96 43
28.Secondary Outcome
Title Number of Participants With the Indicated Worst-case Change From Baseline in the Indicated Chemistry Parameters With Respect to the Normal Range
Hide Description The worst-case change from Baseline in chemistry parameters was measured as decrease to low (DTL), change to normal or no change (CTN/NC), or increase to high (ITH). The worst-case change value could have been measured at any point during the on-therapy period. Participants are counted twice if the participant "Decreased to Low" and "Increased to High" during the on-therapy period.
Time Frame From Randomization until the last clinic visit associated with the study, up until 35 days after the start of the last course of treatment (up to 75 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
Modified ITT Population. Only those participants with available laboratory values (indicated by the "n" in the category titles) were analyzed. Different participants may have been analyzed for different parameters; therefore, the overall number of participants analyzed reflects everyone in the Modified ITT Population.
Arm/Group Title Chemoradiation: Topotecan Plus WBRT Radiation: WBRT Alone
Hide Arm/Group Description:
Participants received topotecan 1.1 milligrams per meters squared per day (mg/m2/day), orally followed approximately 2 hours later by whole-brain radiation therapy (WBRT) 3 Gray (Gy)/day to midline over the course of 10 days. After a 2-week washout period, participants completing chemoradiation and willing to participate in the Continuation Phase of the study received oral topotecan 2.3 mg/m2/day for 5 days, every 21 days, as monotherapy provided the baseline hematologic requirements were met. Monotherapy continued until disease progression or discontinuation. Chemoradiation participants choosing not to participate in the Continuation Phase may have received other chemotherapies or best supportive care, as determined by the investigator.
Participants received WBRT 3 Gy/day for 10 days. Participants may have received other chemotherapies or best supportive care, as determined by the investigator.
Overall Number of Participants Analyzed 235 233
Measure Type: Number
Unit of Measure: participants
Chloride, DTL, n=169, 171 32 21
Chloride, CTN/NC, n=169, 171 116 144
Chloride, ITH, n=169, 171 22 6
Creatinine clearance, DTL, n=159, 145 26 9
Creatinine clearance, CTN/NC, n=159, 145 121 134
Creatinine clearance, ITH, n=159, 145 15 2
Lactate dehydrogenase, DTL, n=169, 168 8 1
Lactate dehydrogenase, CTN/NC, n=169, 168 117 127
Lactate dehydrogenase, ITH, n=169, 168 47 40
Total protein, DTL, n=171, 175 48 36
Total protein, CTN/NC, n=171, 175 119 137
Total protein, ITH, n=171, 175 4 2
Urea/blood urea nitrogen, DTL, n=178, 179 7 4
Urea/blood urea nitrogen, CTN/NC, n=178, 179 139 152
Urea/blood urea nitrogen, ITH, n=178, 179 33 24
Uric acid, DTL, n=159, 152 21 12
Uric acid, CTN/NC, n=159, 152 125 134
Uric acid, ITH, n=159, 152 13 6
Basophils, DTL, n=215, 211 7 1
Basophils, CTN/NC, n=215, 211 186 200
Basophils, ITH, n=215, 211 25 10
Eosinophils, DTL, n=214, 211 28 12
Eosinophils, CTN/NC, n=214, 211 182 191
Eosinophils, ITH, n=214, 211 4 8
Hematocrit, DTL, n=215, 212 98 38
Hematocrit, CTN/NC, n=215, 212 117 169
Hematocrit, ITH, n=215, 212 1 6
Monocytes, DTL, n=216, 212 84 17
Monocytes, CTN/NC, n=216, 212 119 161
Monocytes, ITH, n=216, 212 54 37
Red Blood Cell Count, DTL, n=216, 212 103 38
Red Blood Cell Count, CTN/NC, n=216, 212 113 171
Red Blood Cell Count, ITH, n=216, 212 0 4
29.Secondary Outcome
Title Lesion Assessment and Measurement
Hide Description Lesions were assessed per WHO criteria. For lesion assessment data, see the outcome measure entitled "Number of participants with a complete response (CR) or a partial response (PR) (central nervous system [CNS]-radiologic)."
Time Frame From the time of Randomization until the time of CR or PR (up to 75 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Chemoradiation: Topotecan Plus WBRT Radiation: WBRT Alone
Hide Arm/Group Description:
Participants received topotecan 1.1 milligrams per meters squared per day (mg/m2/day), orally followed approximately 2 hours later by whole-brain radiation therapy (WBRT) 3 Gray (Gy)/day to midline over the course of 10 days. After a 2-week washout period, participants completing chemoradiation and willing to participate in the Continuation Phase of the study received oral topotecan 2.3 mg/m2/day for 5 days, every 21 days, as monotherapy provided the baseline hematologic requirements were met. Monotherapy continued until disease progression or discontinuation. Chemoradiation participants choosing not to participate in the Continuation Phase may have received other chemotherapies or best supportive care, as determined by the investigator.
Participants received WBRT 3 Gy/day for 10 days. Participants may have received other chemotherapies or best supportive care, as determined by the investigator.
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
30.Secondary Outcome
Title Brain Symptoms
Hide Description Brain symptoms were assessed as the number of participants with neurological signs and symptoms. For brain symptom data, see the outcome measures entitled "Number of participants with the indicated investigator assessment for the neurological sign and symptom of X at Baseline, Month 1, and Month 3."
Time Frame Baseline, Month 1, and Month 3
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Chemoradiation: Topotecan Plus WBRT Radiation: WBRT Alone
Hide Arm/Group Description:
Participants received topotecan 1.1 milligrams per meters squared per day (mg/m2/day), orally followed approximately 2 hours later by whole-brain radiation therapy (WBRT) 3 Gray (Gy)/day to midline over the course of 10 days. After a 2-week washout period, participants completing chemoradiation and willing to participate in the Continuation Phase of the study received oral topotecan 2.3 mg/m2/day for 5 days, every 21 days, as monotherapy provided the baseline hematologic requirements were met. Monotherapy continued until disease progression or discontinuation. Chemoradiation participants choosing not to participate in the Continuation Phase may have received other chemotherapies or best supportive care, as determined by the investigator.
Participants received WBRT 3 Gy/day for 10 days. Participants may have received other chemotherapies or best supportive care, as determined by the investigator.
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
31.Secondary Outcome
Title Number of Participants Who Died or Progressed
Hide Description Disease-related events were measured as the number of participants who died or progressed. Progressive disease (PD) is defined as an increase >=25% in any measurable lesion or, in participants with non-measurable disease only, an estimation of an increase >=25%. In both cases, determination of progression included the appearance of any new lesions, or signification worsening of conditions presumed to be related to malignancy. Participants with clinical or laboratory evidence of possible disease progression were to be evaluated radiologically. Data were analyzed with censoring for extended loss to follow-up to account for two or more missed assessments before an event. The date of the last adequate CNS assessment before extended loss to follow-up was used for censored participants.
Time Frame From Randomization until the last clinic visit associated with the study, up until 35 days after the start of the last course of treatment (up to 75 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
mITT Population
Arm/Group Title Chemoradiation: Topotecan Plus WBRT Radiation: WBRT Alone
Hide Arm/Group Description:
Participants received topotecan 1.1 milligrams per meters squared per day (mg/m2/day), orally followed approximately 2 hours later by whole-brain radiation therapy (WBRT) 3 Gray (Gy)/day to midline over the course of 10 days. After a 2-week washout period, participants completing chemoradiation and willing to participate in the Continuation Phase of the study received oral topotecan 2.3 mg/m2/day for 5 days, every 21 days, as monotherapy provided the baseline hematologic requirements were met. Monotherapy continued until disease progression or discontinuation. Chemoradiation participants choosing not to participate in the Continuation Phase may have received other chemotherapies or best supportive care, as determined by the investigator.
Participants received WBRT 3 Gy/day for 10 days. Participants may have received other chemotherapies or best supportive care, as determined by the investigator.
Overall Number of Participants Analyzed 235 233
Measure Type: Number
Unit of Measure: participants
179 161
Time Frame [Not Specified]
Adverse Event Reporting Description Serious adverse events (SAEs) and non-serious AEs were collected in members of the Modified Intent-to-Treat Population, comprised of all randomized participants (par.) who received at least one dose of randomized therapy. Par. were analyzed by the actual treatment received, even if it differed from the treatment to which they were randomized.
 
Arm/Group Title Chemoradiation: Topotecan Plus WBRT Radiation: WBRT Alone
Hide Arm/Group Description Participants received topotecan 1.1 milligrams per meters squared per day (mg/m2/day), orally followed approximately 2 hours later by whole-brain radiation therapy (WBRT) 3 Gray (Gy)/day to midline over the course of 10 days. After a 2-week washout period, participants completing chemoradiation and willing to participate in the Continuation Phase of the study received oral topotecan 2.3 mg/m2/day for 5 days, every 21 days, as monotherapy provided the baseline hematologic requirements were met. Monotherapy continued until disease progression or discontinuation. Chemoradiation participants choosing not to participate in the Continuation Phase may have received other chemotherapies or best supportive care, as determined by the investigator. Participants received WBRT 3 Gy/day for 10 days. Participants may have received other chemotherapies or best supportive care, as determined by the investigator.
All-Cause Mortality
Chemoradiation: Topotecan Plus WBRT Radiation: WBRT Alone
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Chemoradiation: Topotecan Plus WBRT Radiation: WBRT Alone
Affected / at Risk (%) Affected / at Risk (%)
Total   96/235 (40.85%)   43/233 (18.45%) 
Blood and lymphatic system disorders     
Neutropenia  1  22/235 (9.36%)  2/233 (0.86%) 
Thrombocytopenia  1  22/235 (9.36%)  1/233 (0.43%) 
Anaemia  1  16/235 (6.81%)  1/233 (0.43%) 
Febrile neutropenia  1  13/235 (5.53%)  0/233 (0.00%) 
Leukopenia  1  8/235 (3.40%)  1/233 (0.43%) 
Pancytopenia  1  6/235 (2.55%)  0/233 (0.00%) 
Agranulocytosis  1  1/235 (0.43%)  0/233 (0.00%) 
Lymphopenia  1  1/235 (0.43%)  0/233 (0.00%) 
Cardiac disorders     
Atrial fibrillation  1  1/235 (0.43%)  1/233 (0.43%) 
Cardiac failure acute  1  2/235 (0.85%)  0/233 (0.00%) 
Pericarditis  1  1/235 (0.43%)  1/233 (0.43%) 
Acute myocardial infarction  1  1/235 (0.43%)  0/233 (0.00%) 
Cardiopulmonary failure  1  0/235 (0.00%)  1/233 (0.43%) 
Coronary artery insufficiency  1  1/235 (0.43%)  0/233 (0.00%) 
Myocardial infarction  1  0/235 (0.00%)  1/233 (0.43%) 
Myocardial ischaemia  1  1/235 (0.43%)  0/233 (0.00%) 
Endocrine disorders     
Adrenal insufficiency  1  1/235 (0.43%)  0/233 (0.00%) 
Inappropriate antidiuretic hormone secretion  1  1/235 (0.43%)  0/233 (0.00%) 
Gastrointestinal disorders     
Diarrhoea  1  6/235 (2.55%)  0/233 (0.00%) 
Dyspnoea  1  3/235 (1.28%)  1/233 (0.43%) 
Nausea  1  3/235 (1.28%)  2/233 (0.86%) 
Vomiting  1  3/235 (1.28%)  0/233 (0.00%) 
Constipation  1  0/235 (0.00%)  2/233 (0.86%) 
Small intestinal haemorrhage  1  2/235 (0.85%)  0/233 (0.00%) 
Intestinal obstruction  1  0/235 (0.00%)  1/233 (0.43%) 
Intestinal perforation  1  1/235 (0.43%)  0/233 (0.00%) 
Oesophageal stenosis  1  0/235 (0.00%)  1/233 (0.43%) 
Oropharyngeal pain  1  1/235 (0.43%)  0/233 (0.00%) 
Pancreatitis  1  0/235 (0.00%)  1/233 (0.43%) 
General disorders     
Asthenia  1  5/235 (2.13%)  1/233 (0.43%) 
Pyrexia  1  5/235 (2.13%)  1/233 (0.43%) 
Disease progression  1  3/235 (1.28%)  0/233 (0.00%) 
Performance status decreased  1  2/235 (0.85%)  0/233 (0.00%) 
Fatigue  1  1/235 (0.43%)  0/233 (0.00%) 
General physical health deterioration  1  1/235 (0.43%)  0/233 (0.00%) 
Non-cardiac chest pain  1  0/235 (0.00%)  1/233 (0.43%) 
Oedema peripheral  1  0/235 (0.00%)  1/233 (0.43%) 
Pain  1  0/235 (0.00%)  1/233 (0.43%) 
Infections and infestations     
Pneumonia  1  7/235 (2.98%)  6/233 (2.58%) 
Sepsis  1  4/235 (1.70%)  1/233 (0.43%) 
Septic shock  1  1/235 (0.43%)  2/233 (0.86%) 
Bronchitis  1  1/235 (0.43%)  0/233 (0.00%) 
Cellulitis  1  0/235 (0.00%)  1/233 (0.43%) 
Herpes zoster  1  1/235 (0.43%)  0/233 (0.00%) 
Lobar pneumonia  1  1/235 (0.43%)  0/233 (0.00%) 
Lower respiratory tract infection  1  0/235 (0.00%)  1/233 (0.43%) 
Lung abscess  1  1/235 (0.43%)  0/233 (0.00%) 
Oropharyngitis fungal  1  1/235 (0.43%)  0/233 (0.00%) 
Peridiverticular abscess  1  1/235 (0.43%)  0/233 (0.00%) 
Upper respiratory tract infection  1  0/235 (0.00%)  1/233 (0.43%) 
Injury, poisoning and procedural complications     
Accidental overdose  1  2/235 (0.85%)  0/233 (0.00%) 
Overdose  1  2/235 (0.85%)  0/233 (0.00%) 
Face injury  1  1/235 (0.43%)  0/233 (0.00%) 
Femoral neck fracture  1  0/235 (0.00%)  1/233 (0.43%) 
Femur fracture  1  1/235 (0.43%)  0/233 (0.00%) 
Radiation pneumonitis  1  0/235 (0.00%)  1/233 (0.43%) 
Investigations     
Blood bilirubin increased  1  1/235 (0.43%)  0/233 (0.00%) 
Blood creatinine increased  1  1/235 (0.43%)  0/233 (0.00%) 
Weight decreased  1  1/235 (0.43%)  0/233 (0.00%) 
Metabolism and nutrition disorders     
Dehydration  1  5/235 (2.13%)  3/233 (1.29%) 
Hyperglycaemia  1  1/235 (0.43%)  1/233 (0.43%) 
Decreased appetite  1  1/235 (0.43%)  1/233 (0.43%) 
Diabetes mellitus  1  1/235 (0.43%)  1/233 (0.43%) 
Hypernatraemia  1  1/235 (0.43%)  0/233 (0.00%) 
Hyponatraemia  1  1/235 (0.43%)  0/233 (0.00%) 
Malnutrition  1  1/235 (0.43%)  0/233 (0.00%) 
Musculoskeletal and connective tissue disorders     
Muscular weakness  1  1/235 (0.43%)  1/233 (0.43%) 
Back pain  1  0/235 (0.00%)  1/233 (0.43%) 
Musculoskeletal chest pain  1  1/235 (0.43%)  0/233 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Non-small cell lung cancer  1  2/235 (0.85%)  0/233 (0.00%) 
Nervous system disorders     
Brain oedema  1  3/235 (1.28%)  0/233 (0.00%) 
Cerebrovascular accident  1  2/235 (0.85%)  0/233 (0.00%) 
Syncope  1  2/235 (0.85%)  0/233 (0.00%) 
Convulsion  1  1/235 (0.43%)  0/233 (0.00%) 
Encephalopathy  1  1/235 (0.43%)  0/233 (0.00%) 
Grand mal convulsion  1  0/235 (0.00%)  1/233 (0.43%) 
Headache  1  1/235 (0.43%)  0/233 (0.00%) 
Hydrocephalus  1  1/235 (0.43%)  0/233 (0.00%) 
Paraplegia  1  1/235 (0.43%)  0/233 (0.00%) 
Radiculopathy  1  1/235 (0.43%)  0/233 (0.00%) 
Psychiatric disorders     
Confusional state  1  2/235 (0.85%)  0/233 (0.00%) 
Mental status changes  1  1/235 (0.43%)  0/233 (0.00%) 
Renal and urinary disorders     
Haematuria  1  0/235 (0.00%)  1/233 (0.43%) 
Renal failure  1  0/235 (0.00%)  1/233 (0.43%) 
Urinary retention  1  0/235 (0.00%)  1/233 (0.43%) 
Respiratory, thoracic and mediastinal disorders     
Pulmonary embolism  1  1/235 (0.43%)  4/233 (1.72%) 
Chronic obstructive pulmonary disease  1  3/235 (1.28%)  1/233 (0.43%) 
Haemoptysis  1  1/235 (0.43%)  0/233 (0.00%) 
Respiratory failure  1  0/235 (0.00%)  3/233 (1.29%) 
Pneumonitis  1  1/235 (0.43%)  1/233 (0.43%) 
Pulmonary haemorrhage  1  0/235 (0.00%)  2/233 (0.86%) 
Aspiration  1  0/235 (0.00%)  1/233 (0.43%) 
Bronchial obstruction  1  1/235 (0.43%)  0/233 (0.00%) 
Hypoxia  1  0/235 (0.00%)  1/233 (0.43%) 
Lung infiltration  1  0/235 (0.00%)  1/233 (0.43%) 
Pleurisy  1  0/235 (0.00%)  1/233 (0.43%) 
Skin and subcutaneous tissue disorders     
Stevens-Johnson syndrome  1  0/235 (0.00%)  1/233 (0.43%) 
Vascular disorders     
Deep vein thrombosis  1  3/235 (1.28%)  1/233 (0.43%) 
Arterial thrombosis limb  1  0/235 (0.00%)  1/233 (0.43%) 
Jugular vein thrombosis  1  1/235 (0.43%)  0/233 (0.00%) 
Orthostatic hypotension  1  1/235 (0.43%)  0/233 (0.00%) 
Superior vena cava syndrome  1  1/235 (0.43%)  0/233 (0.00%) 
Venous thrombosis  1  0/235 (0.00%)  1/233 (0.43%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Chemoradiation: Topotecan Plus WBRT Radiation: WBRT Alone
Affected / at Risk (%) Affected / at Risk (%)
Total   192/235 (81.70%)   139/233 (59.66%) 
Blood and lymphatic system disorders     
Anaemia  1  7/235 (2.98%)  1/233 (0.43%) 
Thrombocytopenia  1  5/235 (2.13%)  1/233 (0.43%) 
Neutropenia  1  3/235 (1.28%)  0/233 (0.00%) 
Leukopenia  1  2/235 (0.85%)  0/233 (0.00%) 
Coagulopathy  1  0/235 (0.00%)  1/233 (0.43%) 
Febrile neutropenia  1  1/235 (0.43%)  0/233 (0.00%) 
Pancytopenia  1  1/235 (0.43%)  0/233 (0.00%) 
Cardiac disorders     
Atrial fibrillation  1  3/235 (1.28%)  2/233 (0.86%) 
Tachycardia  1  2/235 (0.85%)  3/233 (1.29%) 
Cardiac failure  1  1/235 (0.43%)  1/233 (0.43%) 
Palpitations  1  2/235 (0.85%)  0/233 (0.00%) 
Angina pectoris  1  1/235 (0.43%)  0/233 (0.00%) 
Cardiac failure congestive  1  0/235 (0.00%)  1/233 (0.43%) 
Sinus tachycardia  1  0/235 (0.00%)  1/233 (0.43%) 
Supraventricular extrasystoles  1  0/235 (0.00%)  1/233 (0.43%) 
Ear and labyrinth disorders     
Vertigo  1  4/235 (1.70%)  3/233 (1.29%) 
Tinnitus  1  4/235 (1.70%)  0/233 (0.00%) 
Ear pain  1  2/235 (0.85%)  0/233 (0.00%) 
Ear pruritus  1  2/235 (0.85%)  0/233 (0.00%) 
Auricular swelling  1  0/235 (0.00%)  1/233 (0.43%) 
Deafness  1  0/235 (0.00%)  1/233 (0.43%) 
Hearing impaired  1  1/235 (0.43%)  0/233 (0.00%) 
Hypoacusis  1  1/235 (0.43%)  0/233 (0.00%) 
Endocrine disorders     
Cushingoid  1  1/235 (0.43%)  1/233 (0.43%) 
Inappropriate antidiuretic hormone secretion  1  1/235 (0.43%)  0/233 (0.00%) 
Eye disorders     
Vision blurred  1  4/235 (1.70%)  8/233 (3.43%) 
Visual acuity reduced  1  3/235 (1.28%)  2/233 (0.86%) 
Visual impairment  1  2/235 (0.85%)  2/233 (0.86%) 
Asthenopia  1  1/235 (0.43%)  0/233 (0.00%) 
Blindness  1  0/235 (0.00%)  1/233 (0.43%) 
Conjunctivitis  1  0/235 (0.00%)  1/233 (0.43%) 
Eye inflammation  1  1/235 (0.43%)  0/233 (0.00%) 
Eye pain  1  1/235 (0.43%)  0/233 (0.00%) 
Myopia  1  1/235 (0.43%)  0/233 (0.00%) 
Retinal vascular disorder  1  1/235 (0.43%)  0/233 (0.00%) 
Gastrointestinal disorders     
Nausea  1  64/235 (27.23%)  30/233 (12.88%) 
Vomiting  1  37/235 (15.74%)  24/233 (10.30%) 
Diarrhoea  1  19/235 (8.09%)  8/233 (3.43%) 
Dyspepsia  1  17/235 (7.23%)  10/233 (4.29%) 
Constipation  1  8/235 (3.40%)  10/233 (4.29%) 
Abdominal pain  1  4/235 (1.70%)  6/233 (2.58%) 
Stomatitis  1  7/235 (2.98%)  1/233 (0.43%) 
Abdominal pain upper  1  2/235 (0.85%)  3/233 (1.29%) 
Dysphagia  1  2/235 (0.85%)  3/233 (1.29%) 
Dry mouth  1  2/235 (0.85%)  2/233 (0.86%) 
Gastrooesophageal reflux disease  1  3/235 (1.28%)  0/233 (0.00%) 
Abdominal distension  1  1/235 (0.43%)  1/233 (0.43%) 
Flatulence  1  2/235 (0.85%)  0/233 (0.00%) 
Mouth ulceration  1  2/235 (0.85%)  0/233 (0.00%) 
Rectal haemorrhage  1  1/235 (0.43%)  1/233 (0.43%) 
Abdominal discomfort  1  1/235 (0.43%)  0/233 (0.00%) 
Aphthous stomatitis  1  0/235 (0.00%)  1/233 (0.43%) 
Ascites  1  0/235 (0.00%)  1/233 (0.43%) 
Breath odour  1  0/235 (0.00%)  1/233 (0.43%) 
Faecal incontinence  1  1/235 (0.43%)  0/233 (0.00%) 
Faeces discoloured  1  1/235 (0.43%)  0/233 (0.00%) 
Gastritis  1  0/235 (0.00%)  1/233 (0.43%) 
Gingival pain  1  1/235 (0.43%)  0/233 (0.00%) 
Glossodynia  1  1/235 (0.43%)  0/233 (0.00%) 
Haematochezia  1  1/235 (0.43%)  0/233 (0.00%) 
Haemorrhoids  1  0/235 (0.00%)  1/233 (0.43%) 
Hyperchlorhydria  1  1/235 (0.43%)  0/233 (0.00%) 
Oesophageal pain  1  1/235 (0.43%)  0/233 (0.00%) 
Oral pain  1  0/235 (0.00%)  1/233 (0.43%) 
Retching  1  1/235 (0.43%)  0/233 (0.00%) 
General disorders     
Fatigue  1  39/235 (16.60%)  37/233 (15.88%) 
Asthenia  1  29/235 (12.34%)  19/233 (8.15%) 
Oedema peripheral  1  15/235 (6.38%)  15/233 (6.44%) 
Pyrexia  1  13/235 (5.53%)  5/233 (2.15%) 
Mucosal inflammation  1  7/235 (2.98%)  0/233 (0.00%) 
Gait disturbance  1  2/235 (0.85%)  4/233 (1.72%) 
Face oedema  1  1/235 (0.43%)  3/233 (1.29%) 
Pain  1  1/235 (0.43%)  3/233 (1.29%) 
Chest pain  1  1/235 (0.43%)  2/233 (0.86%) 
Chills  1  2/235 (0.85%)  1/233 (0.43%) 
Non-cardiac chest pain  1  2/235 (0.85%)  1/233 (0.43%) 
Spinal pain  1  1/235 (0.43%)  1/233 (0.43%) 
Chest discomfort  1  0/235 (0.00%)  1/233 (0.43%) 
Early satiety  1  1/235 (0.43%)  0/233 (0.00%) 
Gravitational oedema  1  1/235 (0.43%)  0/233 (0.00%) 
Hyperthermia  1  0/235 (0.00%)  1/233 (0.43%) 
Influenza like illness  1  1/235 (0.43%)  0/233 (0.00%) 
Local swelling  1  0/235 (0.00%)  1/233 (0.43%) 
Localised oedema  1  0/235 (0.00%)  1/233 (0.43%) 
Malaise  1  1/235 (0.43%)  0/233 (0.00%) 
Mucosal erosion  1  1/235 (0.43%)  0/233 (0.00%) 
Oedema  1  1/235 (0.43%)  0/233 (0.00%) 
Swelling  1  1/235 (0.43%)  0/233 (0.00%) 
Hepatobiliary disorders     
Hepatic function abnormal  1  1/235 (0.43%)  0/233 (0.00%) 
Infections and infestations     
Pneumonia  1  4/235 (1.70%)  4/233 (1.72%) 
Oral candidiasis  1  5/235 (2.13%)  2/233 (0.86%) 
Urinary tract infection  1  3/235 (1.28%)  4/233 (1.72%) 
Candidiasis  1  3/235 (1.28%)  2/233 (0.86%) 
Oral fungal infection  1  2/235 (0.85%)  3/233 (1.29%) 
Oropharyngitis fungal  1  1/235 (0.43%)  3/233 (1.29%) 
Upper respiratory tract infection  1  3/235 (1.28%)  1/233 (0.43%) 
Nasopharyngitis  1  1/235 (0.43%)  2/233 (0.86%) 
Rhinitis  1  2/235 (0.85%)  1/233 (0.43%) 
Bronchitis  1  0/235 (0.00%)  2/233 (0.86%) 
Cystitis  1  0/235 (0.00%)  2/233 (0.86%) 
Herpes zoster  1  0/235 (0.00%)  2/233 (0.86%) 
Influenza  1  2/235 (0.85%)  0/233 (0.00%) 
Oesophageal candidiasis  1  2/235 (0.85%)  0/233 (0.00%) 
Oral herpes  1  2/235 (0.85%)  0/233 (0.00%) 
Oropharyngeal candidiasis  1  2/235 (0.85%)  0/233 (0.00%) 
Pharyngitis  1  2/235 (0.85%)  0/233 (0.00%) 
Anal fungal infection  1  1/235 (0.43%)  0/233 (0.00%) 
Fungal infection  1  0/235 (0.00%)  1/233 (0.43%) 
Fungal oesophagitis  1  0/235 (0.00%)  1/233 (0.43%) 
Furuncle  1  0/235 (0.00%)  1/233 (0.43%) 
Herpes simplex  1  1/235 (0.43%)  0/233 (0.00%) 
Infection  1  0/235 (0.00%)  1/233 (0.43%) 
Mastoiditis  1  0/235 (0.00%)  1/233 (0.43%) 
Orchitis  1  0/235 (0.00%)  1/233 (0.43%) 
Otitis media  1  0/235 (0.00%)  1/233 (0.43%) 
Rash pustular  1  1/235 (0.43%)  0/233 (0.00%) 
Respiratory tract infection  1  0/235 (0.00%)  1/233 (0.43%) 
Soft tissue infection  1  1/235 (0.43%)  0/233 (0.00%) 
Tonsillitis  1  1/235 (0.43%)  0/233 (0.00%) 
Tracheobronchitis  1  0/235 (0.00%)  1/233 (0.43%) 
Vaginal infection  1  1/235 (0.43%)  0/233 (0.00%) 
Vulvovaginal mycotic infection  1  1/235 (0.43%)  0/233 (0.00%) 
Injury, poisoning and procedural complications     
Fall  1  1/235 (0.43%)  1/233 (0.43%) 
Thermal burn  1  1/235 (0.43%)  1/233 (0.43%) 
Contusion  1  1/235 (0.43%)  0/233 (0.00%) 
Incision site pain  1  0/235 (0.00%)  1/233 (0.43%) 
Overdose  1  0/235 (0.00%)  1/233 (0.43%) 
Radiation skin injury  1  1/235 (0.43%)  0/233 (0.00%) 
Skin wound  1  1/235 (0.43%)  0/233 (0.00%) 
Investigations     
Weight decreased  1  18/235 (7.66%)  8/233 (3.43%) 
Blood lactate dehydrogenase increased  1  3/235 (1.28%)  2/233 (0.86%) 
Platelet count decreased  1  4/235 (1.70%)  1/233 (0.43%) 
Haemoglobin decreased  1  3/235 (1.28%)  1/233 (0.43%) 
Alanine aminotransferase increased  1  2/235 (0.85%)  1/233 (0.43%) 
Weight increased  1  2/235 (0.85%)  1/233 (0.43%) 
Blood glucose increased  1  0/235 (0.00%)  2/233 (0.86%) 
Neutrophil count decreased  1  2/235 (0.85%)  0/233 (0.00%) 
White blood cell count decreased  1  1/235 (0.43%)  1/233 (0.43%) 
Aspartate aminotransferase increased  1  0/235 (0.00%)  1/233 (0.43%) 
Bacterial test positive  1  1/235 (0.43%)  0/233 (0.00%) 
Blood alkaline phosphatase increased  1  1/235 (0.43%)  0/233 (0.00%) 
Blood bilirubin increased  1  0/235 (0.00%)  1/233 (0.43%) 
Blood creatinine increased  1  0/235 (0.00%)  1/233 (0.43%) 
Blood magnesium increased  1  1/235 (0.43%)  0/233 (0.00%) 
Blood phosphorus decreased  1  0/235 (0.00%)  1/233 (0.43%) 
Blood phosphorus increased  1  1/235 (0.43%)  0/233 (0.00%) 
Blood urea increased  1  0/235 (0.00%)  1/233 (0.43%) 
Blood uric acid increased  1  0/235 (0.00%)  1/233 (0.43%) 
Body temperature increased  1  1/235 (0.43%)  0/233 (0.00%) 
Breath sounds abnormal  1  0/235 (0.00%)  1/233 (0.43%) 
Gamma-glutamyltransferase increased  1  0/235 (0.00%)  1/233 (0.43%) 
International normalised ratio increased  1  1/235 (0.43%)  0/233 (0.00%) 
Metabolism and nutrition disorders     
Decreased appetite  1  28/235 (11.91%)  17/233 (7.30%) 
Increased appetite  1  7/235 (2.98%)  6/233 (2.58%) 
Hypokalaemia  1  9/235 (3.83%)  3/233 (1.29%) 
Hyperglycaemia  1  4/235 (1.70%)  3/233 (1.29%) 
Dehydration  1  2/235 (0.85%)  4/233 (1.72%) 
Hyponatraemia  1  3/235 (1.28%)  1/233 (0.43%) 
Cachexia  1  2/235 (0.85%)  1/233 (0.43%) 
Hypoalbuminaemia  1  3/235 (1.28%)  0/233 (0.00%) 
Hypomagnesaemia  1  1/235 (0.43%)  2/233 (0.86%) 
Hypocalcaemia  1  1/235 (0.43%)  1/233 (0.43%) 
Hyperkalaemia  1  1/235 (0.43%)  0/233 (0.00%) 
Malnutrition  1  1/235 (0.43%)  0/233 (0.00%) 
Polydipsia  1  1/235 (0.43%)  0/233 (0.00%) 
Musculoskeletal and connective tissue disorders     
Muscular weakness  1  29/235 (12.34%)  22/233 (9.44%) 
Pain in extremity  1  8/235 (3.40%)  6/233 (2.58%) 
Arthralgia  1  6/235 (2.55%)  6/233 (2.58%) 
Back pain  1  4/235 (1.70%)  4/233 (1.72%) 
Muscle spasms  1  4/235 (1.70%)  2/233 (0.86%) 
Musculoskeletal pain  1  4/235 (1.70%)  1/233 (0.43%) 
Myalgia  1  2/235 (0.85%)  2/233 (0.86%) 
Joint swelling  1  0/235 (0.00%)  2/233 (0.86%) 
Neck pain  1  2/235 (0.85%)  0/233 (0.00%) 
Bone pain  1  1/235 (0.43%)  0/233 (0.00%) 
Extremity contracture  1  1/235 (0.43%)  0/233 (0.00%) 
Groin pain  1  0/235 (0.00%)  1/233 (0.43%) 
Muscle atrophy  1  0/235 (0.00%)  1/233 (0.43%) 
Musculoskeletal chest pain  1  1/235 (0.43%)  0/233 (0.00%) 
Osteoarthritis  1  1/235 (0.43%)  0/233 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Cancer pain  1  3/235 (1.28%)  3/233 (1.29%) 
Tumour pain  1  2/235 (0.85%)  1/233 (0.43%) 
Lung neoplasm malignant  1  1/235 (0.43%)  0/233 (0.00%) 
Metastases to skin  1  1/235 (0.43%)  0/233 (0.00%) 
Non-small cell lung cancer  1  1/235 (0.43%)  0/233 (0.00%) 
Nervous system disorders     
Headache  1  27/235 (11.49%)  28/233 (12.02%) 
Dizziness  1  27/235 (11.49%)  19/233 (8.15%) 
Somnolence  1  14/235 (5.96%)  14/233 (6.01%) 
Hypoaesthesia  1  6/235 (2.55%)  11/233 (4.72%) 
Ataxia  1  8/235 (3.40%)  6/233 (2.58%) 
Coordination abnormal  1  7/235 (2.98%)  4/233 (1.72%) 
Tremor  1  6/235 (2.55%)  4/233 (1.72%) 
Paraesthesia  1  5/235 (2.13%)  4/233 (1.72%) 
Amnesia  1  2/235 (0.85%)  6/233 (2.58%) 
Dysgeusia  1  6/235 (2.55%)  2/233 (0.86%) 
Aphasia  1  1/235 (0.43%)  6/233 (2.58%) 
Balance disorder  1  0/235 (0.00%)  7/233 (3.00%) 
Convulsion  1  4/235 (1.70%)  1/233 (0.43%) 
Epilepsy  1  1/235 (0.43%)  3/233 (1.29%) 
Neuropathy peripheral  1  2/235 (0.85%)  2/233 (0.86%) 
Peripheral sensory neuropathy  1  2/235 (0.85%)  2/233 (0.86%) 
Speech disorder  1  1/235 (0.43%)  3/233 (1.29%) 
Syncope  1  2/235 (0.85%)  1/233 (0.43%) 
Brain oedema  1  1/235 (0.43%)  1/233 (0.43%) 
Convulsions local  1  2/235 (0.85%)  0/233 (0.00%) 
Hemiparesis  1  0/235 (0.00%)  2/233 (0.86%) 
Hemiplegia  1  1/235 (0.43%)  1/233 (0.43%) 
Loss of consciousness  1  1/235 (0.43%)  1/233 (0.43%) 
Memory impairment  1  1/235 (0.43%)  1/233 (0.43%) 
Psychomotor hyperactivity  1  0/235 (0.00%)  2/233 (0.86%) 
Ageusia  1  0/235 (0.00%)  1/233 (0.43%) 
Alcoholic seizure  1  0/235 (0.00%)  1/233 (0.43%) 
Burning sensation  1  1/235 (0.43%)  0/233 (0.00%) 
Cognitive disorder  1  1/235 (0.43%)  0/233 (0.00%) 
Dysarthria  1  0/235 (0.00%)  1/233 (0.43%) 
Facial paresis  1  1/235 (0.43%)  0/233 (0.00%) 
Hypersomnia  1  0/235 (0.00%)  1/233 (0.43%) 
Hypotonia  1  1/235 (0.43%)  0/233 (0.00%) 
Mental impairment  1  0/235 (0.00%)  1/233 (0.43%) 
Monoplegia  1  1/235 (0.43%)  0/233 (0.00%) 
Neuritis  1  0/235 (0.00%)  1/233 (0.43%) 
Paresis  1  1/235 (0.43%)  0/233 (0.00%) 
Partial seizures  1  1/235 (0.43%)  0/233 (0.00%) 
Peripheral motor neuropathy  1  1/235 (0.43%)  0/233 (0.00%) 
Polyneuropathy  1  0/235 (0.00%)  1/233 (0.43%) 
Sciatica  1  0/235 (0.00%)  1/233 (0.43%) 
Visual field defect  1  0/235 (0.00%)  1/233 (0.43%) 
Psychiatric disorders     
Insomnia  1  17/235 (7.23%)  19/233 (8.15%) 
Confusional state  1  7/235 (2.98%)  11/233 (4.72%) 
Anxiety  1  4/235 (1.70%)  1/233 (0.43%) 
Depression  1  2/235 (0.85%)  2/233 (0.86%) 
Mood altered  1  0/235 (0.00%)  2/233 (0.86%) 
Nervousness  1  0/235 (0.00%)  2/233 (0.86%) 
Delusion  1  0/235 (0.00%)  1/233 (0.43%) 
Depressed mood  1  1/235 (0.43%)  0/233 (0.00%) 
Disorientation  1  0/235 (0.00%)  1/233 (0.43%) 
Initial insomnia  1  0/235 (0.00%)  1/233 (0.43%) 
Mental disorder  1  1/235 (0.43%)  0/233 (0.00%) 
Sleep disorder  1  0/235 (0.00%)  1/233 (0.43%) 
Staring  1  0/235 (0.00%)  1/233 (0.43%) 
Renal and urinary disorders     
Haematuria  1  2/235 (0.85%)  1/233 (0.43%) 
Dysuria  1  2/235 (0.85%)  0/233 (0.00%) 
Pollakiuria  1  1/235 (0.43%)  1/233 (0.43%) 
Chromaturia  1  0/235 (0.00%)  1/233 (0.43%) 
Incontinence  1  0/235 (0.00%)  1/233 (0.43%) 
Nephrolithiasis  1  1/235 (0.43%)  0/233 (0.00%) 
Proteinuria  1  0/235 (0.00%)  1/233 (0.43%) 
Urinary bladder haemorrhage  1  0/235 (0.00%)  1/233 (0.43%) 
Urinary incontinence  1  1/235 (0.43%)  0/233 (0.00%) 
Urinary retention  1  1/235 (0.43%)  0/233 (0.00%) 
Reproductive system and breast disorders     
Epididymitis  1  1/235 (0.43%)  0/233 (0.00%) 
Prostatitis  1  1/235 (0.43%)  0/233 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
Dyspnoea  1  31/235 (13.19%)  20/233 (8.58%) 
Cough  1  26/235 (11.06%)  17/233 (7.30%) 
Epistaxis  1  8/235 (3.40%)  2/233 (0.86%) 
Haemoptysis  1  3/235 (1.28%)  7/233 (3.00%) 
Oropharyngeal pain  1  5/235 (2.13%)  3/233 (1.29%) 
Hiccups  1  3/235 (1.28%)  2/233 (0.86%) 
Dyspnoea exertional  1  1/235 (0.43%)  3/233 (1.29%) 
Hypoxia  1  2/235 (0.85%)  1/233 (0.43%) 
Productive cough  1  1/235 (0.43%)  2/233 (0.86%) 
Dysphonia  1  1/235 (0.43%)  1/233 (0.43%) 
Lung infiltration  1  0/235 (0.00%)  2/233 (0.86%) 
Pleural effusion  1  1/235 (0.43%)  1/233 (0.43%) 
Pulmonary embolism  1  2/235 (0.85%)  0/233 (0.00%) 
Upper-airway cough syndrome  1  2/235 (0.85%)  0/233 (0.00%) 
Wheezing  1  2/235 (0.85%)  0/233 (0.00%) 
Bronchitis chronic  1  1/235 (0.43%)  0/233 (0.00%) 
Chronic obstructive pulmonary disease  1  1/235 (0.43%)  0/233 (0.00%) 
Hydrothorax  1  1/235 (0.43%)  0/233 (0.00%) 
Increased upper airway secretion  1  1/235 (0.43%)  0/233 (0.00%) 
Laryngeal inflammation  1  0/235 (0.00%)  1/233 (0.43%) 
Pharyngeal inflammation  1  0/235 (0.00%)  1/233 (0.43%) 
Pneumothorax  1  1/235 (0.43%)  0/233 (0.00%) 
Pulmonary hypertension  1  0/235 (0.00%)  1/233 (0.43%) 
Rales  1  0/235 (0.00%)  1/233 (0.43%) 
Respiratory failure  1  1/235 (0.43%)  0/233 (0.00%) 
Respiratory tract congestion  1  0/235 (0.00%)  1/233 (0.43%) 
Rhinorrhoea  1  1/235 (0.43%)  0/233 (0.00%) 
Skin and subcutaneous tissue disorders     
Alopecia  1  21/235 (8.94%)  17/233 (7.30%) 
Erythema  1  4/235 (1.70%)  1/233 (0.43%) 
Pruritus  1  5/235 (2.13%)  0/233 (0.00%) 
Rash  1  2/235 (0.85%)  3/233 (1.29%) 
Dry skin  1  1/235 (0.43%)  2/233 (0.86%) 
Swelling face  1  1/235 (0.43%)  2/233 (0.86%) 
Acne  1  1/235 (0.43%)  1/233 (0.43%) 
Ecchymosis  1  1/235 (0.43%)  1/233 (0.43%) 
Night sweats  1  1/235 (0.43%)  1/233 (0.43%) 
Skin disorder  1  0/235 (0.00%)  2/233 (0.86%) 
Skin ulcer  1  1/235 (0.43%)  1/233 (0.43%) 
Dermatitis allergic  1  0/235 (0.00%)  1/233 (0.43%) 
Haemorrhage subcutaneous  1  1/235 (0.43%)  0/233 (0.00%) 
Increased tendency to bruise  1  0/235 (0.00%)  1/233 (0.43%) 
Petechiae  1  1/235 (0.43%)  0/233 (0.00%) 
Rash papular  1  1/235 (0.43%)  0/233 (0.00%) 
Skin exfoliation  1  0/235 (0.00%)  1/233 (0.43%) 
Vascular disorders     
Hypotension  1  6/235 (2.55%)  0/233 (0.00%) 
Deep vein thrombosis  1  1/235 (0.43%)  2/233 (0.86%) 
Hypertension  1  2/235 (0.85%)  1/233 (0.43%) 
Flushing  1  1/235 (0.43%)  1/233 (0.43%) 
Phlebitis  1  2/235 (0.85%)  0/233 (0.00%) 
Haematoma  1  0/235 (0.00%)  1/233 (0.43%) 
Hot flush  1  0/235 (0.00%)  1/233 (0.43%) 
Orthostatic hypotension  1  0/235 (0.00%)  1/233 (0.43%) 
Thrombophlebitis superficial  1  1/235 (0.43%)  0/233 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
Results Point of Contact
Name/Title: GSK Response Center
Organization: GlaxoSmithKline
Phone: 866-435-7343
Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT00390806     History of Changes
Other Study ID Numbers: HYT105962
First Submitted: October 19, 2006
First Posted: October 20, 2006
Results First Submitted: March 8, 2013
Results First Posted: January 20, 2014
Last Update Posted: January 20, 2014