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Trial record 8 of 23 for:    Pancreatic Cancer | ( Map: Hong Kong )

A Dose-Escalation to Rash Study of Tarceva (Erlotinib) Plus Gemcitabine in Patients With Metastatic Pancreatic Cancer

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ClinicalTrials.gov Identifier: NCT00652366
Recruitment Status : Completed
First Posted : April 3, 2008
Results First Posted : February 11, 2015
Last Update Posted : February 11, 2015
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Pancreatic Cancer
Interventions Drug: Erlotinib, escalating dose
Drug: Erlotinib, standard dose
Drug: Gemcitabine
Enrollment 467
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Gemcitabine (G) Plus (+) Erlotinib (E): Rash ≥ Grade 2 G+E Standard Dose: Rash Grade Less Than (<) 2 G+E Escalating Dose: Rash Grade < 2 G+E: No Rash Non-Eligibl G+E: Early Drop Out
Hide Arm/Group Description Participants began a 4 week run-in period where they received gemcitabine, 1000 milligrams per square meter (mg/m^2), intravenously (IV), on Days 1, 8, 15, 22 until development of a rash Grade ≥ 2. Participants also received erlotinib, 100 milligrams (mg), orally (PO) as a film-coated tablet, once daily until development of a rash Grade ≥ 2. Participants were not randomized to a treatment arm, but continued to receive the standard treatment of gemcitabine, 1000 mg/m^2, IV, on Days 1, 8, and 15 of consecutive 4 week cycles, and erlotinib, 100 mg, PO as a film-coated tablet, once daily until disease progression, unacceptable toxicity, or withdrawal for up to 46 months. Participants completed a 4 week run-in period where they received gemcitabine, 1000 mg/m^2, IV, on Days 1, 8, 15, 22. Participants also received erlotinib, 100 mg, PO as a film-coated tablet, once daily for 4 weeks. Participants without evidence of clinical progression and who had not developed rash Grade ≥ 2 or any other toxicity leading to dose adjustments or discontinuation were randomized to receive gemcitabine, 1000 mg/m^2, IV, on Days 1, 8, and 15 of consecutive 4 week cycles and erlotinib, 100 mg, PO as a film-coated tablet, once daily until disease progression or unacceptable toxicity, or withdrawal for up to 46 months. Participants completed a 4 week run-in period where they received gemcitabine, 1000 mg/m^2, IV, on Days 1, 8, 15, 22. Participants also received erlotinib, 100 mg, PO as a film-coated tablet, once daily for 4 weeks. Participants without evidence of clinical progression and who had not developed rash Grade ≥ 2 or any other toxicity leading to dose adjustments or discontinuation were randomized to receive erlotinib, beginning at 150 milligrams per day (mg/day), PO as a film-coated tablet, once daily and increasing in increments of 50 mg every 2 weeks up to a maximum of 250 mg/day, until development of a Grade ≥ 2 rash, or occurrence of other, non-rash, dose-limiting toxicity; treatment was continued until disease progression, unacceptable toxicity, death or withdrawal for up to 46 months. Those participants also received gemcitabine, 1000 mg/m^2, IV, on Days 1, 8, and 15 of consecutive 4 week cycles until disease progression, unacceptable toxicity, or withdrawal for up to 46 months. Participants began a 4 week run-in period where they received gemcitabine, 1000 mg/m^2, IV, on Days 1, 8, 15, 22 until the appearance of evidence of clinical progression or other toxicity leading to dose adjustments or discontinuation. Participants also received erlotinib, 100 mg, PO as a film-coated tablet, once daily until the appearance of evidence of clinical progression or other toxicity leading to dose adjustments or discontinuation. Participants were not randomized to a treatment arm, but continued to receive the standard treatment of gemcitabine, 1000 mg/m^2, IV, on Days 1, 8, and 15 of consecutive 4 week cycles, and erlotinib, 100 mg, PO as a film-coated tablet, once daily until disease progression, unacceptable toxicity, or withdrawal for up to 46 months. Participants began a 4 week run-in period where they received gemcitabine, 1000 mg/m^2, IV, on Days 1, 8, 15, 22 for up to 4 weeks. Participants also received erlotinib, 100 mg, PO as a film-coated tablet, once daily for up to 4 weeks.
Period Title: Overall Study
Started 106 75 71 179 36
Completed 0 0 0 0 0
Not Completed 106 75 71 179 36
Reason Not Completed
Adverse Event             8             4             7             17             13
Death             5             4             1             8             5
Lack of Efficacy             84             58             53             133             13
Violation of Selection Criteria             0             0             1             0             0
Protocol Violation             1             0             0             0             0
Refused treatment             3             7             6             17             5
Not specified             5             2             3             4             0
Arm/Group Title G+E: Rash ≥ Grade 2 G+E Standard Dose: Rash Grade < 2 G+E Escalating Dose: Rash Grade < 2 G+E: No Rash Non-Eligible G+E: Early Drop Out Total
Hide Arm/Group Description Participants began a 4 week run-in period where they received gemcitabine, 1000 mg/m^2, IV, on Days 1, 8, 15, 22 until development of a rash Grade ≥ 2. Participants also received erlotinib, 100 mg, PO as a film-coated tablet, once daily until development of a rash Grade ≥ 2. Participants were not randomized to a treatment arm, but continued to receive the standard treatment of gemcitabine, 1000 mg/m^2, IV, on Days 1, 8, and 15 of consecutive 4 week cycles, and erlotinib, 100 mg, PO as a film-coated tablet, once daily until disease progression, unacceptable toxicity, or withdrawal for up to 46 months. Participants completed a 4 week run-in period where they received gemcitabine, 1000 mg/m^2, IV, on Days 1, 8, 15, 22. Participants also received erlotinib, 100 mg, PO as a film-coated tablet, once daily for 4 weeks. Participants without evidence of clinical progression and who had not developed rash Grade ≥ 2 or any other toxicity leading to dose adjustments or discontinuation were randomized to receive gemcitabine, 1000 mg/m^2, IV, on Days 1, 8, and 15 of consecutive 4 week cycles and erlotinib, 100 mg, PO as a film-coated tablet, once daily until disease progression or unacceptable toxicity, or withdrawal for up to 46 months. Participants completed a 4 week run-in period where they received gemcitabine, 1000 mg/m^2, IV, on Days 1, 8, 15, 22. Participants also received erlotinib, 100 mg, PO as a film-coated tablet, once daily for 4 weeks. Participants without evidence of clinical progression and who had not developed rash Grade ≥ 2 or any other toxicity leading to dose adjustments or discontinuation were randomized to receive erlotinib, beginning at 150 mg/day, PO as a film-coated tablet, once daily and increasing in increments of 50 mg every 2 weeks up to a maximum of 250 mg/day, until development of a Grade 2 rash, or occurrence of other, non-rash, dose-limiting toxicity; treatment was continued until disease progression, unacceptable toxicity, death or withdrawal for up to 46 months. Those participants also received gemcitabine, 1000 mg/m^2, IV, on Days 1, 8, and 15 of consecutive 4 week cycles until disease progression, unacceptable toxicity, or withdrawal for up to 46 months. Participants began a 4 week run-in period where they received gemcitabine, 1000 mg/m^2, IV, on Days 1, 8, 15, 22 until the appearance of evidence of clinical progression or other toxicity leading to dose adjustments or discontinuation. Participants also received erlotinib, 100 mg, PO as a film-coated tablet, once daily until the appearance of evidence of clinical progression or other toxicity leading to dose adjustments or discontinuation. Participants were not randomized to a treatment arm, but continued to receive the standard treatment of gemcitabine, 1000 mg/m^2, IV, on Days 1, 8, and 15 of consecutive 4 week cycles, and erlotinib, 100 mg, PO as a film-coated tablet, once daily until disease progression, unacceptable toxicity, or withdrawal for up to 46 months. Participants began a 4 week run-in period where they received gemcitabine, 1000 mg/m^2, IV, on Days 1, 8, 15, 22 for up to 4 weeks. Participants also received erlotinib, 100 mg, PO as a film-coated tablet, once daily for up to 4 weeks. Total of all reporting groups
Overall Number of Baseline Participants 106 75 70 179 36 466
Hide Baseline Analysis Population Description
Safety analysis population (SAP): all participants who received at least 1 dose of the trial medication and had at least 1 safety follow-up, whether withdrawn prematurely or not.
Age, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 106 participants 75 participants 70 participants 179 participants 36 participants 466 participants
Less Than (<) 65 Years 66 43 34 97 21 261
≥ 65 Years 40 32 36 82 15 205
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 106 participants 75 participants 70 participants 179 participants 36 participants 466 participants
Female
41
  38.7%
41
  54.7%
34
  48.6%
77
  43.0%
15
  41.7%
208
  44.6%
Male
65
  61.3%
34
  45.3%
36
  51.4%
102
  57.0%
21
  58.3%
258
  55.4%
1.Primary Outcome
Title Percentage of Participants Who Died Assessed From Point of Randomization
Hide Description Overall survival (OS) assessed from the point of randomization was defined as the time from randomization to the date of death due to any cause. Participants still alive at the time of analysis were censored at the date they were last known to be alive.
Time Frame Randomization [Day 1 of Cycle 2 (4-week cycles)] and weekly thereafter for up to 46 months.
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set (FAS): all randomized participants.
Arm/Group Title G+E Standard Dose: Rash Grade < 2 G+E Escalating Dose: Rash Grade < 2
Hide Arm/Group Description:
Participants completed a 4 week run-in period where they received gemcitabine, 1000 mg/m^2, IV, on Days 1, 8, 15, 22. Participants also received erlotinib, 100 mg, PO as a film-coated tablet, once daily for 4 weeks. Participants without evidence of clinical progression and who had not developed rash Grade ≥ 2 or any other toxicity leading to dose adjustments or discontinuation were randomized to receive gemcitabine, 1000 mg/m^2, IV, on Days 1, 8, and 15 of consecutive 4 week cycles and erlotinib, 100 mg, PO as a film-coated tablet, once daily until disease progression or unacceptable toxicity, or withdrawal for up to 46 months.
Participants completed a 4 week run-in period where they received gemcitabine, 1000 mg/m^2, IV, on Days 1, 8, 15, 22. Participants also received erlotinib, 100 mg, PO as a film-coated tablet, once daily for 4 weeks. Participants without evidence of clinical progression and who had not developed rash Grade ≥ 2 or any other toxicity leading to dose adjustments or discontinuation were randomized to receive erlotinib, beginning at 150 mg/day, PO as a film-coated tablet, once daily and increasing in increments of 50 mg every 2 weeks up to a maximum of 250 mg/day, until development of a Grade 2 rash, or occurrence of other, non-rash, dose-limiting toxicity; treatment was continued until disease progression, unacceptable toxicity, death or withdrawal for up to 46 months. Those participants also received gemcitabine, 1000 mg/m^2, IV, on Days 1, 8, and 15 of consecutive 4 week cycles until disease progression, unacceptable toxicity, or withdrawal for up to 46 months.
Overall Number of Participants Analyzed 75 70
Measure Type: Number
Unit of Measure: percentage of participants
81.3 85.7
2.Primary Outcome
Title OS Assessed From Point of Randomization
Hide Description OS assessed from the point of randomization was defined as the median time, in months, from randomization to the date of death due to any cause. Participants still alive at the time of analysis were censored at the date they were last known to be alive. The 95 percent (%) confidence interval (CI) was determined using Kaplan-Meier methodology.
Time Frame Randomization [Day 1 of Cycle 2 (4-week cycles)] and weekly thereafter for up to 46 months.
Hide Outcome Measure Data
Hide Analysis Population Description
FAS
Arm/Group Title G+E Standard Dose: Rash Grade < 2 G+E Escalating Dose: Rash Grade < 2
Hide Arm/Group Description:
Participants completed a 4 week run-in period where they received gemcitabine, 1000 mg/m^2, IV, on Days 1, 8, 15, 22. Participants also received erlotinib, 100 mg, PO as a film-coated tablet, once daily for 4 weeks. Participants without evidence of clinical progression and who had not developed rash Grade ≥ 2 or any other toxicity leading to dose adjustments or discontinuation were randomized to receive gemcitabine, 1000 mg/m^2, IV, on Days 1, 8, and 15 of consecutive 4 week cycles and erlotinib, 100 mg, PO as a film-coated tablet, once daily until disease progression or unacceptable toxicity, or withdrawal for up to 46 months
Participants completed a 4 week run-in period where they received gemcitabine, 1000 mg/m^2, IV, on Days 1, 8, 15, 22. Participants also received erlotinib, 100 mg, PO as a film-coated tablet, once daily for 4 weeks. Participants without evidence of clinical progression and who had not developed rash Grade ≥ 2 or any other toxicity leading to dose adjustments or discontinuation were randomized to receive erlotinib, beginning at 150 mg/day, PO as a film-coated tablet, once daily and increasing in increments of 50 mg every 2 weeks up to a maximum of 250 mg/day, until development of a Grade 2 rash, or occurrence of other, non-rash, dose-limiting toxicity; treatment was continued until disease progression, unacceptable toxicity, death or withdrawal for up to 46 months. Those participants also received gemcitabine, 1000 mg/m^2, IV, on Days 1, 8, and 15 of consecutive 4 week cycles until disease progression, unacceptable toxicity, or withdrawal for up to 46 months.
Overall Number of Participants Analyzed 75 70
Median (95% Confidence Interval)
Unit of Measure: months
8.4
(6.4 to 10.0)
7.0
(5.8 to 8.3)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection G+E Standard Dose: Rash Grade < 2, G+E Escalating Dose: Rash Grade < 2
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2026
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.26
Confidence Interval (2-Sided) 95%
0.88 to 1.80
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Percentage of Participants With Disease Progression or Death as Assessed From Point of Randomization
Hide Description Progression-free survival (PFS) as assessed from the point of randomization was defined as the time from randomization to the first occurrence of progressive disease (PD) according to the Response Evaluation Criteria in Solid Tumors (RECIST) or death due to any cause. For target lesions (TLs), PD was defined as at least a 20% increase in the sum of longest diameter (SLD) of TLs, taking as reference the smallest SLD recorded since the treatment started. For non-target lesions (NTLs), PD was defined as unequivocal progression of existing NTLs. Participants who had neither progressed nor died at time of analysis were censored at the date of last tumor assessment.
Time Frame Randomization [Day 1 of Cycle 2 (4-week cycles)] and weekly thereafter for up to 46 months.
Hide Outcome Measure Data
Hide Analysis Population Description
FAS
Arm/Group Title G+E Standard Dose: Rash Grade < 2 G+E Escalating Dose: Rash Grade < 2
Hide Arm/Group Description:
Participants completed a 4 week run-in period where they received gemcitabine, 1000 mg/m^2, IV, on Days 1, 8, 15, 22. Participants also received erlotinib, 100 mg, PO as a film-coated tablet, once daily for 4 weeks. Participants without evidence of clinical progression and who had not developed rash Grade ≥ 2 or any other toxicity leading to dose adjustments or discontinuation were randomized to receive gemcitabine, 1000 mg/m^2, IV, on Days 1, 8, and 15 of consecutive 4 week cycles and erlotinib, 100 mg, PO as a film-coated tablet, once daily until disease progression or unacceptable toxicity, or withdrawal for up to 46 months.
Participants completed a 4 week run-in period where they received gemcitabine, 1000 mg/m^2, IV, on Days 1, 8, 15, 22. Participants also received erlotinib, 100 mg, PO as a film-coated tablet, once daily for 4 weeks. Participants without evidence of clinical progression and who had not developed rash Grade ≥ 2 or any other toxicity leading to dose adjustments or discontinuation were randomized to receive erlotinib, beginning at 150 mg/day, PO as a film-coated tablet, once daily and increasing in increments of 50 mg every 2 weeks up to a maximum of 250 mg/day, until development of a Grade 2 rash, or occurrence of other, non-rash, dose-limiting toxicity; treatment was continued until disease progression, unacceptable toxicity, death or withdrawal for up to 46 months. Those participants also received gemcitabine, 1000 mg/m^2, IV, on Days 1, 8, and 15 of consecutive 4 week cycles until disease progression, unacceptable toxicity, or withdrawal for up to 46 months.
Overall Number of Participants Analyzed 75 70
Measure Type: Number
Unit of Measure: percentage of participants
90.7 88.6
4.Secondary Outcome
Title PFS Assessed From Point of Randomization
Hide Description PFS assessed from the point of randomization was defined as the median time, in weeks, from randomization to disease progression or death due to any cause. Participants who had neither progressed nor died at time of analysis were censored at the date of last tumor assessment. The 95% CI was determined using Kaplan-Meier methodology.
Time Frame Randomization [Day 1 of Cycle 2 (4-week cycles)] and weekly thereafter for up to 46 months.
Hide Outcome Measure Data
Hide Analysis Population Description
FAS
Arm/Group Title G+E Standard Dose: Rash Grade < 2 G+E Escalating Dose: Rash Grade < 2
Hide Arm/Group Description:
Participants completed a 4 week run-in period where they received gemcitabine, 1000 mg/m^2, IV, on Days 1, 8, 15, 22. Participants also received erlotinib, 100 mg, PO as a film-coated tablet, once daily for 4 weeks. Participants without evidence of clinical progression and who had not developed rash Grade ≥ 2 or any other toxicity leading to dose adjustments or discontinuation were randomized to receive gemcitabine, 1000 mg/m^2, IV, on Days 1, 8, and 15 of consecutive 4 week cycles and erlotinib, 100 mg, PO as a film-coated tablet, once daily until disease progression or unacceptable toxicity, or withdrawal for up to 46 months.
Participants completed a 4 week run-in period where they received gemcitabine, 1000 mg/m^2, IV, on Days 1, 8, 15, 22. Participants also received erlotinib, 100 mg, PO as a film-coated tablet, once daily for 4 weeks. Participants without evidence of clinical progression and who had not developed rash Grade ≥ 2 or any other toxicity leading to dose adjustments or discontinuation were randomized to receive erlotinib, beginning at 150 mg/day, PO as a film-coated tablet, once daily and increasing in increments of 50 mg every 2 weeks up to a maximum of 250 mg/day, until development of a Grade 2 rash, or occurrence of other, non-rash, dose-limiting toxicity; treatment was continued until disease progression, unacceptable toxicity, death or withdrawal for up to 46 months. Those participants also received gemcitabine, 1000 mg/m^2, IV, on Days 1, 8, and 15 of consecutive 4 week cycles until disease progression, unacceptable toxicity, or withdrawal for up to 46 months.
Overall Number of Participants Analyzed 75 70
Median (95% Confidence Interval)
Unit of Measure: weeks
19.4
(16.0 to 26.9)
15.3
(11.3 to 19.1)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection G+E Standard Dose: Rash Grade < 2, G+E Escalating Dose: Rash Grade < 2
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6298
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.09
Confidence Interval (2-Sided) 95%
0.77 to 1.54
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Percentage of Participants With a Best Overall Response (BOR) of Confirmed Complete Response (CR) or Partial Response (PR) According to RECIST
Hide Description BOR was defined as a confirmed CR or PR for at least 4 weeks. CR was defined as the disappearance of all TLs. PR was defined as at least a 30% decrease in the SLD of the TLs, taking as a reference the baseline (BL) SLD. The 95% CI for one sample binomial was determined using Pearson-Clopper method.
Time Frame BL, Weeks 8, 16, 24, 32, 40, every 12 weeks thereafter until disease progression for up to 46 months.
Hide Outcome Measure Data
Hide Analysis Population Description
FAS
Arm/Group Title G+E Standard Dose: Rash Grade < 2 G+E Escalating Dose: Rash Grade < 2
Hide Arm/Group Description:
Participants completed a 4 week run-in period where they received gemcitabine, 1000 mg/m^2, IV, on Days 1, 8, 15, 22. Participants also received erlotinib, 100 mg, PO as a film-coated tablet, once daily for 4 weeks. Participants without evidence of clinical progression and who had not developed rash Grade ≥ 2 or any other toxicity leading to dose adjustments or discontinuation were randomized to receive gemcitabine, 1000 mg/m^2, IV, on Days 1, 8, and 15 of consecutive 4 week cycles and erlotinib, 100 mg, PO as a film-coated tablet, once daily until disease progression or unacceptable toxicity, or withdrawal for up to 46 months.
Participants completed a 4 week run-in period where they received gemcitabine, 1000 mg/m^2, IV, on Days 1, 8, 15, 22. Participants also received erlotinib, 100 mg, PO as a film-coated tablet, once daily for 4 weeks. Participants without evidence of clinical progression and who had not developed rash Grade ≥ 2 or any other toxicity leading to dose adjustments or discontinuation were randomized to receive erlotinib, beginning at 150 mg/day, PO as a film-coated tablet, once daily and increasing in increments of 50 mg every 2 weeks up to a maximum of 250 mg/day, until development of a Grade 2 rash, or occurrence of other, non-rash, dose-limiting toxicity; treatment was continued until disease progression, unacceptable toxicity, death or withdrawal for up to 46 months. Those participants also received gemcitabine, 1000 mg/m^2, IV, on Days 1, 8, and 15 of consecutive 4 week cycles until disease progression, unacceptable toxicity, or withdrawal for up to 46 months.
Overall Number of Participants Analyzed 75 70
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
14.7
(7.6 to 24.7)
8.6
(3.2 to 17.7)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection G+E Standard Dose: Rash Grade < 2, G+E Escalating Dose: Rash Grade < 2
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2543
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Response Rates
Estimated Value -6.10
Confidence Interval (2-Sided) 95%
-17.2 to 5.0
Estimation Comments Approximate 95% CI for the difference of two rates was determined using the Hauck-Anderson method.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection G+E Standard Dose: Rash Grade < 2, G+E Escalating Dose: Rash Grade < 2
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.55
Confidence Interval (2-Sided) 95%
0.19 to 1.56
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Percentage of Participants With a CR, PR, Stable Disease (SD), or PD According to RECIST
Hide Description CR was defined as the disappearance of all TLs. PR was defined as at least a 30% decrease in the SLD of the TLs, taking as a reference the BL SLD SD was defined as neither sufficient decrease in SLD to qualify for PR nor sufficient increase in SLD to qualify for PD. PD was defined as at least a 20% increase in the SLD of TLs, taking as reference the smallest SLD recorded since the treatment started. The 95% CI for one sample binomial was determined using the Pearson-Clopper method.
Time Frame BL, Weeks 8, 16, 24, 32, 40, every 12 weeks thereafter until disease progression for up to 46 months.
Hide Outcome Measure Data
Hide Analysis Population Description
FAS
Arm/Group Title G+E Standard Dose: Rash Grade < 2 G+E Escalating Dose: Rash Grade < 2
Hide Arm/Group Description:
Participants completed a 4 week run-in period where they received gemcitabine, 1000 mg/m^2, IV, on Days 1, 8, 15, 22. Participants also received erlotinib, 100 mg, PO as a film-coated tablet, once daily for 4 weeks. Participants without evidence of clinical progression and who had not developed rash Grade ≥ 2 or any other toxicity leading to dose adjustments or discontinuation were randomized to receive gemcitabine, 1000 mg/m^2, IV, on Days 1, 8, and 15 of consecutive 4 week cycles and erlotinib, 100 mg, PO as a film-coated tablet, once daily until disease progression or unacceptable toxicity, or withdrawal for up to 46 months.
Participants completed a 4 week run-in period where they received gemcitabine, 1000 mg/m^2, IV, on Days 1, 8, 15, 22. Participants also received erlotinib, 100 mg, PO as a film-coated tablet, once daily for 4 weeks. Participants without evidence of clinical progression and who had not developed rash Grade ≥ 2 or any other toxicity leading to dose adjustments or discontinuation were randomized to receive erlotinib, beginning at 150 mg/day, PO as a film-coated tablet, once daily and increasing in increments of 50 mg every 2 weeks up to a maximum of 250 mg/day, until development of a Grade 2 rash, or occurrence of other, non-rash, dose-limiting toxicity; treatment was continued until disease progression, unacceptable toxicity, death or withdrawal for up to 46 months. Those participants also received gemcitabine, 1000 mg/m^2, IV, on Days 1, 8, and 15 of consecutive 4 week cycles until disease progression, unacceptable toxicity, or withdrawal for up to 46 months.
Overall Number of Participants Analyzed 75 70
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
CR
0.0
(0.0 to 4.8)
1.4
(0.0 to 7.7)
PR
14.7
(7.6 to 24.7)
7.1
(2.4 to 15.9)
SD
58.7
(46.7 to 69.9)
72.9
(60.9 to 82.8)
PD
25.3
(16.0 to 36.7)
12.9
(6.1 to 23.0)
Missing (no response assessment)
1.3 [1] 
(NA to NA)
5.7 [1] 
(NA to NA)
[1]
95% CI was not determined for missing responses.
7.Secondary Outcome
Title Percentage of Participants With SD (Maintained for at Least 8 Weeks) or CR or PR (Maintained for at Least 4 Weeks) According to RECIST
Hide Description Disease control was defined as a participant with a response of CR or PR for at least 4 weeks at any time during treatment, or SD that was maintained for at least 8 weeks after the start of treatment. The 95% CI for one sample binomial was determined using the Pearson-Clopper method.
Time Frame BL, Weeks 8, 16, 24, 32, 40, every 12 weeks thereafter until disease progression for up to 46 months.
Hide Outcome Measure Data
Hide Analysis Population Description
FAS
Arm/Group Title G+E Standard Dose: Rash Grade < 2 G+E Escalating Dose: Rash Grade < 2
Hide Arm/Group Description:
Participants completed a 4 week run-in period where they received gemcitabine, 1000 mg/m^2, IV, on Days 1, 8, 15, 22. Participants also received erlotinib, 100 mg, PO as a film-coated tablet, once daily for 4 weeks. Participants without evidence of clinical progression and who had not developed rash Grade ≥ 2 or any other toxicity leading to dose adjustments or discontinuation were randomized to receive gemcitabine, 1000 mg/m^2, IV, on Days 1, 8, and 15 of consecutive 4 week cycles and erlotinib, 100 mg, PO as a film-coated tablet, once daily until disease progression or unacceptable toxicity, or withdrawal for up to 46 months.
Participants completed a 4 week run-in period where they received gemcitabine, 1000 mg/m^2, IV, on Days 1, 8, 15, 22. Participants also received erlotinib, 100 mg, PO as a film-coated tablet, once daily for 4 weeks. Participants without evidence of clinical progression and who had not developed rash Grade ≥ 2 or any other toxicity leading to dose adjustments or discontinuation were randomized to receive erlotinib, beginning at 150 mg/day, PO as a film-coated tablet, once daily and increasing in increments of 50 mg every 2 weeks up to a maximum of 250 mg/day, until development of a Grade 2 rash, or occurrence of other, non-rash, dose-limiting toxicity; treatment was continued until disease progression, unacceptable toxicity, death or withdrawal for up to 46 months. Those participants also received gemcitabine, 1000 mg/m^2, IV, on Days 1, 8, and 15 of consecutive 4 week cycles until disease progression, unacceptable toxicity, or withdrawal for up to 46 months.
Overall Number of Participants Analyzed 75 70
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
62.7
(50.7 to 73.6)
47.1
(35.1 to 59.4)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection G+E Standard Dose: Rash Grade < 2, G+E Escalating Dose: Rash Grade < 2
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0603
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Disease Control Rates
Estimated Value -15.52
Confidence Interval (2-Sided) 95%
-32.4 to 1.3
Estimation Comments Approximate 95% CI for the difference of two rates was determined using the Hauck-Anderson method.
8.Secondary Outcome
Title Percentage of Participants Who Died as Assessed From Start of 4-Week Run-In
Hide Description OS assessed from the start of the 4-week run in period was defined as the time from BL to the date of death due to any cause. Participants still alive at the time of analysis were censored at the date they were last known to be alive.
Time Frame BL and weekly thereafter for up to 46 months.
Hide Outcome Measure Data
Hide Analysis Population Description
FAS
Arm/Group Title G+E: Rash ≥ Grade 2 G+E Standard Dose: Rash Grade < 2 G+E Escalating Dose: Rash Grade < 2
Hide Arm/Group Description:
Participants began a 4 week run-in period where they received gemcitabine, 1000 mg/m^2, IV, on Days 1, 8, 15, 22 until development of a rash Grade ≥ 2. Participants also received erlotinib, 100 mg, PO as a film-coated tablet, once daily until development of a rash Grade ≥ 2. Participants were not randomized to a treatment arm, but continued to receive the standard treatment of gemcitabine, 1000 mg/m^2, IV, on Days 1, 8, and 15 of consecutive 4 week cycles, and erlotinib, 100 mg, PO as a film-coated tablet, once daily until disease progression, unacceptable toxicity, or withdrawal for up to 46 months.
Participants completed a 4 week run-in period where they received gemcitabine, 1000 mg/m^2, IV, on Days 1, 8, 15, 22. Participants also received erlotinib, 100 mg, PO as a film-coated tablet, once daily for 4 weeks. Participants without evidence of clinical progression and who had not developed rash Grade ≥ 2 or any other toxicity leading to dose adjustments or discontinuation were randomized to receive gemcitabine, 1000 mg/m^2, IV, on Days 1, 8, and 15 of consecutive 4 week cycles and erlotinib, 100 mg, PO as a film-coated tablet, once daily until disease progression or unacceptable toxicity, or withdrawal for up to 46 months.
Participants completed a 4 week run-in period where they received gemcitabine, 1000 mg/m^2, IV, on Days 1, 8, 15, 22. Participants also received erlotinib, 100 mg, PO as a film-coated tablet, once daily for 4 weeks. Participants without evidence of clinical progression and who had not developed rash Grade ≥ 2 or any other toxicity leading to dose adjustments or discontinuation were randomized to receive erlotinib, beginning at 150 mg/day, PO as a film-coated tablet, once daily and increasing in increments of 50 mg every 2 weeks up to a maximum of 250 mg/day, until development of a Grade 2 rash, or occurrence of other, non-rash, dose-limiting toxicity; treatment was continued until disease progression, unacceptable toxicity, death or withdrawal for up to 46 months. Those participants also received gemcitabine, 1000 mg/m^2, IV, on Days 1, 8, and 15 of consecutive 4 week cycles until disease progression, unacceptable toxicity, or withdrawal for up to 46 months.
Overall Number of Participants Analyzed 106 75 70
Measure Type: Number
Unit of Measure: percentage of participants
84.9 81.3 85.7
9.Secondary Outcome
Title OS Assessed From Start of 4-Week Run-In
Hide Description OS assessed from the start of the 4-week run in period was defined as the median time, in months, from BL to the date of death, due to any cause. Participants who were still alive at the time of analysis were censored at the date they were last known to be alive. The 95% CI was determined using Kaplan-Meier methodology.
Time Frame BL and weekly thereafter for up to 46 months.
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Hide Analysis Population Description
FAS
Arm/Group Title G+E: Rash ≥ Grade 2 G+E Standard Dose: Rash Grade < 2 G+E Escalating Dose: Rash Grade < 2
Hide Arm/Group Description:
Participants began a 4 week run-in period where they received gemcitabine, 1000 mg/m^2, IV, on Days 1, 8, 15, 22 until development of a rash Grade ≥ 2. Participants also received erlotinib, 100 mg, PO as a film-coated tablet, once daily until development of a rash Grade ≥ 2. Participants were not randomized to a treatment arm, but continued to receive the standard treatment of gemcitabine, 1000 mg/m^2, IV, on Days 1, 8, and 15 of consecutive 4 week cycles, and erlotinib, 100 mg, PO as a film-coated tablet, once daily until disease progression, unacceptable toxicity, or withdrawal for up to 46 months.
Participants completed a 4 week run-in period where they received gemcitabine, 1000 mg/m^2, IV, on Days 1, 8, 15, 22. Participants also received erlotinib, 100 mg, PO as a film-coated tablet, once daily for 4 weeks. Participants without evidence of clinical progression and who had not developed rash Grade ≥ 2 or any other toxicity leading to dose adjustments or discontinuation were randomized to receive gemcitabine, 1000 mg/m^2, IV, on Days 1, 8, and 15 of consecutive 4 week cycles and erlotinib, 100 mg, PO as a film-coated tablet, once daily until disease progression or unacceptable toxicity, or withdrawal for up to 46 months.
Participants completed a 4 week run-in period where they received gemcitabine, 1000 mg/m^2, IV, on Days 1, 8, 15, 22. Participants also received erlotinib, 100 mg, PO as a film-coated tablet, once daily for 4 weeks. Participants without evidence of clinical progression and who had not developed rash Grade ≥ 2 or any other toxicity leading to dose adjustments or discontinuation were randomized to receive erlotinib, beginning at 150 mg/day, PO as a film-coated tablet, once daily and increasing in increments of 50 mg every 2 weeks up to a maximum of 250 mg/day, until development of a Grade 2 rash, or occurrence of other, non-rash, dose-limiting toxicity; treatment was continued until disease progression, unacceptable toxicity, death or withdrawal for up to 46 months. Those participants also received gemcitabine, 1000 mg/m^2, IV, on Days 1, 8, and 15 of consecutive 4 week cycles until disease progression, unacceptable toxicity, or withdrawal for up to 46 months.
Overall Number of Participants Analyzed 106 75 70
Median (95% Confidence Interval)
Unit of Measure: months
7.9
(7.1 to 8.8)
9.3
(7.3 to 10.9)
8.0
(6.8 to 9.2)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection G+E: Rash ≥ Grade 2, G+E Standard Dose: Rash Grade < 2
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2678
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.83
Confidence Interval (2-Sided) 95%
0.60 to 1.15
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection G+E: Rash ≥ Grade 2, G+E Escalating Dose: Rash Grade < 2
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8449
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.03
Confidence Interval (2-Sided) 95%
0.74 to 1.43
Estimation Comments [Not Specified]
10.Secondary Outcome
Title Percentage of Participants With Disease Progression or Death as Assessed From the Start of 4-Week Run-In
Hide Description PFS as assessed from the start of 4-week run-in was defined as the time from BL to the first occurrence of PD according to RECIST or death due to any cause. For TLs, PD was defined as at least a 20% increase in the SLD of TLs, taking as reference the smallest SLD recorded since the treatment started. For NTLs, PD was defined as unequivocal progression of existing NTLs. Participants who had neither progressed nor died at time of analysis were censored at the date of last tumor assessment.
Time Frame BL, Weeks 8, 16, 24, 32, 40, every 12 weeks thereafter until disease progression or death for up to 46 months.
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Hide Analysis Population Description
FAS
Arm/Group Title G+E: Rash ≥ Grade 2 G+E Standard Dose: Rash Grade < 2 G+E Escalating Dose: Rash Grade < 2
Hide Arm/Group Description:
Participants began a 4 week run-in period where they received gemcitabine, 1000 mg/m^2, IV, on Days 1, 8, 15, 22 until development of a rash Grade ≥ 2. Participants also received erlotinib, 100 mg, PO as a film-coated tablet, once daily until development of a rash Grade ≥ 2. Participants were not randomized to a treatment arm, but continued to receive the standard treatment of gemcitabine, 1000 mg/m^2, IV, on Days 1, 8, and 15 of consecutive 4 week cycles, and erlotinib, 100 mg, PO as a film-coated tablet, once daily until disease progression, unacceptable toxicity, or withdrawal for up to 46 months.
Participants completed a 4 week run-in period where they received gemcitabine, 1000 mg/m^2, IV, on Days 1, 8, 15, 22. Participants also received erlotinib, 100 mg, PO as a film-coated tablet, once daily for 4 weeks. Participants without evidence of clinical progression and who had not developed rash Grade ≥ 2 or any other toxicity leading to dose adjustments or discontinuation were randomized to receive gemcitabine, 1000 mg/m^2, IV, on Days 1, 8, and 15 of consecutive 4 week cycles and erlotinib, 100 mg, PO as a film-coated tablet, once daily until disease progression or unacceptable toxicity, or withdrawal for up to 46 months.
Participants completed a 4 week run-in period where they received gemcitabine, 1000 mg/m^2, IV, on Days 1, 8, 15, 22. Participants also received erlotinib, 100 mg, PO as a film-coated tablet, once daily for 4 weeks. Participants without evidence of clinical progression and who had not developed rash Grade ≥ 2 or any other toxicity leading to dose adjustments or discontinuation were randomized to receive erlotinib, beginning at 150 mg/day, PO as a film-coated tablet, once daily and increasing in increments of 50 mg every 2 weeks up to a maximum of 250 mg/day, until development of a Grade 2 rash, or occurrence of other, non-rash, dose-limiting toxicity; treatment was continued until disease progression, unacceptable toxicity, death or withdrawal for up to 46 months. Those participants also received gemcitabine, 1000 mg/m^2, IV, on Days 1, 8, and 15 of consecutive 4 week cycles until disease progression, unacceptable toxicity, or withdrawal for up to 46 months.
Overall Number of Participants Analyzed 106 75 70
Measure Type: Number
Unit of Measure: percentage of participants
90.6 90.7 88.6
11.Secondary Outcome
Title PFS Assessed From the Start of 4-Week Run-In
Hide Description PFS assessed from the start of 4-week run-in was defined as the median time, in weeks, from BL to disease progression or death due to any cause. Participants who had neither progressed nor died at time of analysis were censored at the date of last tumor assessment. The 95% CI was determined using Kaplan-Meier methodology.
Time Frame BL, Weeks 8, 16, 24, 32, 40, every 12 weeks thereafter until disease progression or death for up to 46 months.
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Hide Analysis Population Description
FAS; only participants with an event of PD or death were included in the analysis.
Arm/Group Title G+E: Rash ≥ Grade 2 G+E Standard Dose: Rash Grade < 2 G+E Escalating Dose: Rash Grade < 2
Hide Arm/Group Description:
Participants began a 4 week run-in period where they received gemcitabine, 1000 milligrams per square meter (mg/m^2), intravenously (IV), on Days 1, 8, 15, 22 until development of a rash Grade ≥ 2. Participants also received erlotinib, 100 milligrams (mg), orally (PO) as a film-coated tablet, once daily until development of a rash Grade ≥ 2. Participants were not randomized to a treatment arm, but continued to receive the standard treatment of gemcitabine, 1000 mg/m^2, IV, on Days 1, 8, and 15 of consecutive 4 week cycles, and erlotinib, 100 mg, PO as a film-coated tablet, once daily until disease progression, unacceptable toxicity, or withdrawal for up to 46 months.
Participants completed a 4 week run-in period where they received gemcitabine, 1000 mg/m^2, IV, on Days 1, 8, 15, 22. Participants also received erlotinib, 100 mg, PO as a film-coated tablet, once daily for 4 weeks. Participants without evidence of clinical progression and who had not developed rash Grade ≥ 2 or any other toxicity leading to dose adjustments or discontinuation were randomized to receive gemcitabine, 1000 mg/m^2, IV, on Days 1, 8, and 15 of consecutive 4 week cycles and erlotinib, 100 mg, PO as a film-coated tablet, once daily until disease progression or unacceptable toxicity, or withdrawal for up to 46 months.
Participants completed a 4 week run-in period where they received gemcitabine, 1000 mg/m^2, IV, on Days 1, 8, 15, 22. Participants also received erlotinib, 100 mg, PO as a film-coated tablet, once daily for 4 weeks. Participants without evidence of clinical progression and who had not developed rash Grade ≥ 2 or any other toxicity leading to dose adjustments or discontinuation were randomized to receive erlotinib, beginning at 150 mg/day, PO as a film-coated tablet, once daily and increasing in increments of 50 mg every 2 weeks up to a maximum of 250 mg/day, until development of a Grade 2 rash, or occurrence of other, non-rash, dose-limiting toxicity; treatment was continued until disease progression, unacceptable toxicity, death or withdrawal for up to 46 months. Those participants also received gemcitabine, 1000 mg/m^2, IV, on Days 1, 8, and 15 of consecutive 4 week cycles until disease progression, unacceptable toxicity, or withdrawal for up to 46 months.
Overall Number of Participants Analyzed 96 68 62
Median (95% Confidence Interval)
Unit of Measure: weeks
17.1
(16.0 to 22.7)
23.4
(20.0 to 31.0)
19.3
(15.3 to 23.1)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection G+E: Rash ≥ Grade 2, G+E Standard Dose: Rash Grade < 2
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0217
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.69
Confidence Interval (2-Sided) 95%
0.51 to 0.95
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection G+E: Rash ≥ Grade 2, G+E Escalating Dose: Rash Grade < 2
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1596
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.79
Confidence Interval (2-Sided) 95%
0.57 to 1.10
Estimation Comments [Not Specified]
Time Frame Adverse events (AEs) were collected up to 28 days after discontinuation of study drug, drug-related serious AEs (SAEs) continued to be collected thereafter.
Adverse Event Reporting Description All participants who received at least 1 dose of trial medication and had at least 1 safety follow-up were included in the safety analysis population.
 
Arm/Group Title G+E: Rash ≥ Grade 2 G+E Standard Dose: Rash Grade < 2 G+E Escalating Dose: Rash Grade < 2 G+E: No Rash Non-Eligible G+E: Early Drop Out
Hide Arm/Group Description Participants began a 4 week run-in period where they received gemcitabine, 1000 mg/m^2, IV, on Days 1, 8, 15, 22 until development of a rash Grade ≥ 2. Participants also received erlotinib, 100 mg, PO as a film-coated tablet, once daily until development of a rash Grade ≥ 2. Participants were not randomized to a treatment arm, but continued to receive the standard treatment of gemcitabine, 1000 mg/m^2, IV, on Days 1, 8, and 15 of consecutive 4 week cycles, and erlotinib, 100 mg, PO as a film-coated tablet, once daily until disease progression, unacceptable toxicity, or withdrawal for up to 46 months. Participants completed a 4 week run-in period where they received gemcitabine, 1000 mg/m^2, IV, on Days 1, 8, 15, 22. Participants also received erlotinib, 100 mg, PO as a film-coated tablet, once daily for 4 weeks. Participants without evidence of clinical progression and who had not developed rash Grade ≥ 2 or any other toxicity leading to dose adjustments or discontinuation were randomized to receive gemcitabine, 1000 mg/m^2, IV, on Days 1, 8, and 15 of consecutive 4 week cycles and erlotinib, 100 mg, PO as a film-coated tablet, once daily until disease progression or unacceptable toxicity, or withdrawal for up to 46 months. Participants completed a 4 week run-in period where they received gemcitabine, 1000 mg/m^2, IV, on Days 1, 8, 15, 22. Participants also received erlotinib, 100 mg, PO as a film-coated tablet, once daily for 4 weeks. Participants without evidence of clinical progression and who had not developed rash Grade ≥ 2 or any other toxicity leading to dose adjustments or discontinuation were randomized to receive erlotinib, beginning at 150 mg/day, PO as a film-coated tablet, once daily and increasing in increments of 50 mg every 2 weeks up to a maximum of 250 mg/day, until development of a Grade 2 rash, or occurrence of other, non-rash, dose-limiting toxicity; treatment was continued until disease progression, unacceptable toxicity, death or withdrawal for up to 46 months. Those participants also received gemcitabine, 1000 mg/m^2, IV, on Days 1, 8, and 15 of consecutive 4 week cycles until disease progression, unacceptable toxicity, or withdrawal for up to 46 months. Participants began a 4 week run-in period where they received gemcitabine, 1000 mg/m^2, IV, on Days 1, 8, 15, 22 until the appearance of evidence of clinical progression or other toxicity leading to dose adjustments or discontinuation. Participants also received erlotinib, 100 mg, PO as a film-coated tablet, once daily until the appearance of evidence of clinical progression or other toxicity leading to dose adjustments or discontinuation. Participants were not randomized to a treatment arm, but continued to receive the standard treatment of gemcitabine, 1000 mg/m^2, IV, on Days 1, 8, and 15 of consecutive 4 week cycles, and erlotinib, 100 mg, PO as a film-coated tablet, once daily until disease progression, unacceptable toxicity, or withdrawal for up to 46 months. Participants began a 4 week run-in period where they received gemcitabine, 1000 mg/m^2, IV, on Days 1, 8, 15, 22 for up to 4 weeks. Participants also received erlotinib, 100 mg, PO as a film-coated tablet, once daily for up to 4 weeks.
All-Cause Mortality
G+E: Rash ≥ Grade 2 G+E Standard Dose: Rash Grade < 2 G+E Escalating Dose: Rash Grade < 2 G+E: No Rash Non-Eligible G+E: Early Drop Out
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
G+E: Rash ≥ Grade 2 G+E Standard Dose: Rash Grade < 2 G+E Escalating Dose: Rash Grade < 2 G+E: No Rash Non-Eligible G+E: Early Drop Out
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   39/105 (37.14%)   24/77 (31.17%)   20/71 (28.17%)   64/178 (35.96%)   22/36 (61.11%) 
Blood and lymphatic system disorders           
Anaemia * 1  4/105 (3.81%)  1/77 (1.30%)  2/71 (2.82%)  6/178 (3.37%)  2/36 (5.56%) 
Febrile neutropenia * 1  2/105 (1.90%)  1/77 (1.30%)  1/71 (1.41%)  0/178 (0.00%)  1/36 (2.78%) 
Thrombocytopenia * 1  1/105 (0.95%)  0/77 (0.00%)  0/71 (0.00%)  1/178 (0.56%)  0/36 (0.00%) 
Neutropenia * 1  0/105 (0.00%)  0/77 (0.00%)  0/71 (0.00%)  1/178 (0.56%)  0/36 (0.00%) 
Cardiac disorders           
Acute myocardial infarction * 1  0/105 (0.00%)  0/77 (0.00%)  0/71 (0.00%)  2/178 (1.12%)  1/36 (2.78%) 
Atrial fibrillation * 1  0/105 (0.00%)  1/77 (1.30%)  1/71 (1.41%)  0/178 (0.00%)  0/36 (0.00%) 
Angina pectoris * 1  1/105 (0.95%)  0/77 (0.00%)  0/71 (0.00%)  0/178 (0.00%)  0/36 (0.00%) 
Cardiac arrest * 1  1/105 (0.95%)  0/77 (0.00%)  0/71 (0.00%)  0/178 (0.00%)  0/36 (0.00%) 
Cardiac failure * 1  0/105 (0.00%)  1/77 (1.30%)  0/71 (0.00%)  0/178 (0.00%)  0/36 (0.00%) 
Myocardial infarction * 1  1/105 (0.95%)  0/77 (0.00%)  0/71 (0.00%)  0/178 (0.00%)  0/36 (0.00%) 
Gastrointestinal disorders           
Abdominal pain * 1  3/105 (2.86%)  0/77 (0.00%)  1/71 (1.41%)  4/178 (2.25%)  2/36 (5.56%) 
Diarrhoea * 1  2/105 (1.90%)  4/77 (5.19%)  1/71 (1.41%)  2/178 (1.12%)  1/36 (2.78%) 
Vomiting * 1  2/105 (1.90%)  1/77 (1.30%)  1/71 (1.41%)  5/178 (2.81%)  1/36 (2.78%) 
Gastrointestinal haemorrhage * 1  0/105 (0.00%)  0/77 (0.00%)  1/71 (1.41%)  5/178 (2.81%)  0/36 (0.00%) 
Ileus * 1  0/105 (0.00%)  0/77 (0.00%)  0/71 (0.00%)  2/178 (1.12%)  1/36 (2.78%) 
Peritonitis * 1  0/105 (0.00%)  0/77 (0.00%)  0/71 (0.00%)  2/178 (1.12%)  1/36 (2.78%) 
Rectal haemorrhage * 1  2/105 (1.90%)  0/77 (0.00%)  0/71 (0.00%)  0/178 (0.00%)  0/36 (0.00%) 
Upper gastrointestinal haemorrhage * 1  0/105 (0.00%)  0/77 (0.00%)  0/71 (0.00%)  2/178 (1.12%)  0/36 (0.00%) 
Abdominal pain upper * 1  0/105 (0.00%)  0/77 (0.00%)  1/71 (1.41%)  0/178 (0.00%)  0/36 (0.00%) 
Ascites * 1  0/105 (0.00%)  0/77 (0.00%)  0/71 (0.00%)  0/178 (0.00%)  1/36 (2.78%) 
Duodenal ulcer * 1  0/105 (0.00%)  0/77 (0.00%)  0/71 (0.00%)  1/178 (0.56%)  0/36 (0.00%) 
Enteritis * 1  1/105 (0.95%)  0/77 (0.00%)  0/71 (0.00%)  0/178 (0.00%)  0/36 (0.00%) 
Faecaloma * 1  0/105 (0.00%)  0/77 (0.00%)  0/71 (0.00%)  1/178 (0.56%)  0/36 (0.00%) 
Gastric haemorrhage * 1  0/105 (0.00%)  0/77 (0.00%)  0/71 (0.00%)  0/178 (0.00%)  1/36 (2.78%) 
Intestinal fistula * 1  0/105 (0.00%)  0/77 (0.00%)  0/71 (0.00%)  0/178 (0.00%)  1/36 (2.78%) 
Jejunal perforation * 1  1/105 (0.95%)  0/77 (0.00%)  0/71 (0.00%)  0/178 (0.00%)  0/36 (0.00%) 
Melaena * 1  0/105 (0.00%)  0/77 (0.00%)  0/71 (0.00%)  0/178 (0.00%)  1/36 (2.78%) 
Nausea * 1  0/105 (0.00%)  0/77 (0.00%)  0/71 (0.00%)  0/178 (0.00%)  1/36 (2.78%) 
Obstruction gastric * 1  0/105 (0.00%)  0/77 (0.00%)  0/71 (0.00%)  1/178 (0.56%)  0/36 (0.00%) 
Oesophagitis haemorrhagic * 1  1/105 (0.95%)  0/77 (0.00%)  0/71 (0.00%)  0/178 (0.00%)  0/36 (0.00%) 
General disorders           
Pyrexia * 1  3/105 (2.86%)  2/77 (2.60%)  3/71 (4.23%)  9/178 (5.06%)  2/36 (5.56%) 
General physical health deterioration * 1  2/105 (1.90%)  1/77 (1.30%)  1/71 (1.41%)  1/178 (0.56%)  1/36 (2.78%) 
Chills * 1  0/105 (0.00%)  0/77 (0.00%)  0/71 (0.00%)  1/178 (0.56%)  1/36 (2.78%) 
Death * 1  0/105 (0.00%)  0/77 (0.00%)  0/71 (0.00%)  0/178 (0.00%)  1/36 (2.78%) 
Device occlusion * 1  0/105 (0.00%)  0/77 (0.00%)  1/71 (1.41%)  0/178 (0.00%)  0/36 (0.00%) 
Fatigue * 1  1/105 (0.95%)  0/77 (0.00%)  0/71 (0.00%)  0/178 (0.00%)  0/36 (0.00%) 
Malaise * 1  0/105 (0.00%)  1/77 (1.30%)  0/71 (0.00%)  0/178 (0.00%)  0/36 (0.00%) 
Oedema * 1  0/105 (0.00%)  0/77 (0.00%)  1/71 (1.41%)  0/178 (0.00%)  0/36 (0.00%) 
Oedema peripheral * 1  0/105 (0.00%)  0/77 (0.00%)  0/71 (0.00%)  1/178 (0.56%)  0/36 (0.00%) 
Pain * 1  0/105 (0.00%)  0/77 (0.00%)  1/71 (1.41%)  0/178 (0.00%)  0/36 (0.00%) 
Sudden death * 1  0/105 (0.00%)  0/77 (0.00%)  0/71 (0.00%)  0/178 (0.00%)  1/36 (2.78%) 
Ulcer haemorrhage * 1  0/105 (0.00%)  1/77 (1.30%)  0/71 (0.00%)  0/178 (0.00%)  0/36 (0.00%) 
Hepatobiliary disorders           
Cholangitis * 1  2/105 (1.90%)  1/77 (1.30%)  2/71 (2.82%)  3/178 (1.69%)  0/36 (0.00%) 
Bile duct obstruction * 1  0/105 (0.00%)  1/77 (1.30%)  0/71 (0.00%)  2/178 (1.12%)  0/36 (0.00%) 
Jaundice * 1  0/105 (0.00%)  0/77 (0.00%)  1/71 (1.41%)  2/178 (1.12%)  0/36 (0.00%) 
Cholangitis acute * 1  0/105 (0.00%)  0/77 (0.00%)  2/71 (2.82%)  0/178 (0.00%)  0/36 (0.00%) 
Cholecystitis * 1  0/105 (0.00%)  0/77 (0.00%)  0/71 (0.00%)  1/178 (0.56%)  0/36 (0.00%) 
Cholelithiasis * 1  0/105 (0.00%)  0/77 (0.00%)  0/71 (0.00%)  1/178 (0.56%)  0/36 (0.00%) 
Cholestasis * 1  0/105 (0.00%)  0/77 (0.00%)  0/71 (0.00%)  1/178 (0.56%)  0/36 (0.00%) 
Hepatic failure * 1  0/105 (0.00%)  0/77 (0.00%)  0/71 (0.00%)  1/178 (0.56%)  0/36 (0.00%) 
Infections and infestations           
Pneumonia * 1  1/105 (0.95%)  2/77 (2.60%)  1/71 (1.41%)  6/178 (3.37%)  0/36 (0.00%) 
Infection * 1  1/105 (0.95%)  0/77 (0.00%)  0/71 (0.00%)  4/178 (2.25%)  0/36 (0.00%) 
Sepsis * 1  2/105 (1.90%)  0/77 (0.00%)  0/71 (0.00%)  3/178 (1.69%)  0/36 (0.00%) 
Cellulitis * 1  0/105 (0.00%)  1/77 (1.30%)  0/71 (0.00%)  2/178 (1.12%)  0/36 (0.00%) 
Biliary sepsis * 1  1/105 (0.95%)  0/77 (0.00%)  1/71 (1.41%)  0/178 (0.00%)  0/36 (0.00%) 
Bronchopneumonia * 1  1/105 (0.95%)  0/77 (0.00%)  1/71 (1.41%)  0/178 (0.00%)  0/36 (0.00%) 
Device related infection * 1  0/105 (0.00%)  0/77 (0.00%)  1/71 (1.41%)  1/178 (0.56%)  0/36 (0.00%) 
Escherichia sepsis * 1  1/105 (0.95%)  0/77 (0.00%)  1/71 (1.41%)  0/178 (0.00%)  0/36 (0.00%) 
Lower respiratory tract infection * 1  1/105 (0.95%)  0/77 (0.00%)  0/71 (0.00%)  1/178 (0.56%)  0/36 (0.00%) 
Urinary tract infection * 1  0/105 (0.00%)  0/77 (0.00%)  0/71 (0.00%)  2/178 (1.12%)  0/36 (0.00%) 
Abdominal abscess * 1  0/105 (0.00%)  1/77 (1.30%)  0/71 (0.00%)  0/178 (0.00%)  0/36 (0.00%) 
Biliary tract infection * 1  0/105 (0.00%)  1/77 (1.30%)  0/71 (0.00%)  0/178 (0.00%)  0/36 (0.00%) 
Bronchitis * 1  0/105 (0.00%)  1/77 (1.30%)  0/71 (0.00%)  0/178 (0.00%)  0/36 (0.00%) 
Clostridial infection * 1  0/105 (0.00%)  0/77 (0.00%)  0/71 (0.00%)  1/178 (0.56%)  0/36 (0.00%) 
Erysipelas * 1  0/105 (0.00%)  0/77 (0.00%)  0/71 (0.00%)  1/178 (0.56%)  0/36 (0.00%) 
Febrile infection * 1  0/105 (0.00%)  0/77 (0.00%)  1/71 (1.41%)  0/178 (0.00%)  0/36 (0.00%) 
Gastrointestinal viral infection * 1  0/105 (0.00%)  0/77 (0.00%)  0/71 (0.00%)  1/178 (0.56%)  0/36 (0.00%) 
Klebsiella infection * 1  1/105 (0.95%)  0/77 (0.00%)  0/71 (0.00%)  0/178 (0.00%)  0/36 (0.00%) 
Orchitis * 1  0/105 (0.00%)  0/77 (0.00%)  1/71 (1.41%)  0/178 (0.00%)  0/36 (0.00%) 
Parainfluenzae virus infection * 1  0/105 (0.00%)  0/77 (0.00%)  0/71 (0.00%)  0/178 (0.00%)  1/36 (2.78%) 
Peritonitis bacterial * 1  0/105 (0.00%)  0/77 (0.00%)  1/71 (1.41%)  0/178 (0.00%)  0/36 (0.00%) 
Pyelonephritis acute * 1  1/105 (0.95%)  0/77 (0.00%)  0/71 (0.00%)  0/178 (0.00%)  0/36 (0.00%) 
Skin infection * 1  0/105 (0.00%)  0/77 (0.00%)  0/71 (0.00%)  1/178 (0.56%)  0/36 (0.00%) 
Subcutaneous abscess * 1  0/105 (0.00%)  0/77 (0.00%)  0/71 (0.00%)  1/178 (0.56%)  0/36 (0.00%) 
Superinfection * 1  0/105 (0.00%)  0/77 (0.00%)  0/71 (0.00%)  1/178 (0.56%)  0/36 (0.00%) 
Viral infection * 1  1/105 (0.95%)  0/77 (0.00%)  0/71 (0.00%)  0/178 (0.00%)  0/36 (0.00%) 
Vulvitis * 1  1/105 (0.95%)  0/77 (0.00%)  0/71 (0.00%)  0/178 (0.00%)  0/36 (0.00%) 
Injury, poisoning and procedural complications           
Face injury * 1  0/105 (0.00%)  0/77 (0.00%)  1/71 (1.41%)  0/178 (0.00%)  0/36 (0.00%) 
Hip fracture * 1  0/105 (0.00%)  0/77 (0.00%)  0/71 (0.00%)  1/178 (0.56%)  0/36 (0.00%) 
Investigations           
Blood glucose increased * 1  0/105 (0.00%)  0/77 (0.00%)  1/71 (1.41%)  0/178 (0.00%)  0/36 (0.00%) 
Liver function test abnormal * 1  0/105 (0.00%)  0/77 (0.00%)  0/71 (0.00%)  1/178 (0.56%)  0/36 (0.00%) 
Metabolism and nutrition disorders           
Dehydration * 1  2/105 (1.90%)  0/77 (0.00%)  0/71 (0.00%)  1/178 (0.56%)  1/36 (2.78%) 
Diabetes mellitus * 1  0/105 (0.00%)  0/77 (0.00%)  2/71 (2.82%)  0/178 (0.00%)  0/36 (0.00%) 
Decreased appetite * 1  0/105 (0.00%)  0/77 (0.00%)  0/71 (0.00%)  0/178 (0.00%)  1/36 (2.78%) 
Hyperglycaemia * 1  0/105 (0.00%)  0/77 (0.00%)  0/71 (0.00%)  0/178 (0.00%)  1/36 (2.78%) 
Hypoglycaemia * 1  1/105 (0.95%)  0/77 (0.00%)  0/71 (0.00%)  0/178 (0.00%)  0/36 (0.00%) 
Hypokalaemia * 1  0/105 (0.00%)  0/77 (0.00%)  0/71 (0.00%)  1/178 (0.56%)  0/36 (0.00%) 
Musculoskeletal and connective tissue disorders           
Back pain * 1  0/105 (0.00%)  0/77 (0.00%)  0/71 (0.00%)  1/178 (0.56%)  0/36 (0.00%) 
Muscular weakness * 1  0/105 (0.00%)  0/77 (0.00%)  0/71 (0.00%)  1/178 (0.56%)  0/36 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)           
Cancer pain * 1  0/105 (0.00%)  0/77 (0.00%)  0/71 (0.00%)  1/178 (0.56%)  0/36 (0.00%) 
Paraganglion neoplasm * 1  0/105 (0.00%)  0/77 (0.00%)  0/71 (0.00%)  1/178 (0.56%)  0/36 (0.00%) 
Nervous system disorders           
Cerebrovascular accident * 1  1/105 (0.95%)  0/77 (0.00%)  0/71 (0.00%)  0/178 (0.00%)  2/36 (5.56%) 
Ischaemic stroke * 1  0/105 (0.00%)  1/77 (1.30%)  0/71 (0.00%)  0/178 (0.00%)  1/36 (2.78%) 
Presyncope * 1  0/105 (0.00%)  1/77 (1.30%)  0/71 (0.00%)  1/178 (0.56%)  0/36 (0.00%) 
Cerebral haemorrhage * 1  0/105 (0.00%)  0/77 (0.00%)  0/71 (0.00%)  1/178 (0.56%)  0/36 (0.00%) 
Dizziness * 1  0/105 (0.00%)  0/77 (0.00%)  0/71 (0.00%)  1/178 (0.56%)  0/36 (0.00%) 
Haemorrhagic cerebral infarction * 1  0/105 (0.00%)  0/77 (0.00%)  0/71 (0.00%)  1/178 (0.56%)  0/36 (0.00%) 
Hypoaesthesia * 1  0/105 (0.00%)  0/77 (0.00%)  0/71 (0.00%)  1/178 (0.56%)  0/36 (0.00%) 
Loss of consciousness * 1  0/105 (0.00%)  0/77 (0.00%)  0/71 (0.00%)  0/178 (0.00%)  1/36 (2.78%) 
Polyneuropathy * 1  0/105 (0.00%)  0/77 (0.00%)  0/71 (0.00%)  1/178 (0.56%)  0/36 (0.00%) 
Sensory loss * 1  0/105 (0.00%)  0/77 (0.00%)  0/71 (0.00%)  0/178 (0.00%)  1/36 (2.78%) 
Transient ischaemic attack * 1  0/105 (0.00%)  1/77 (1.30%)  0/71 (0.00%)  0/178 (0.00%)  0/36 (0.00%) 
Psychiatric disorders           
Psychotic disorder * 1  0/105 (0.00%)  0/77 (0.00%)  0/71 (0.00%)  0/178 (0.00%)  1/36 (2.78%) 
Suicide attempt * 1  0/105 (0.00%)  0/77 (0.00%)  0/71 (0.00%)  1/178 (0.56%)  0/36 (0.00%) 
Renal and urinary disorders           
Renal failure acute * 1  0/105 (0.00%)  0/77 (0.00%)  0/71 (0.00%)  2/178 (1.12%)  0/36 (0.00%) 
Renal failure chronic * 1  0/105 (0.00%)  0/77 (0.00%)  1/71 (1.41%)  0/178 (0.00%)  0/36 (0.00%) 
Renal tubular necrosis * 1  1/105 (0.95%)  0/77 (0.00%)  0/71 (0.00%)  0/178 (0.00%)  0/36 (0.00%) 
Respiratory, thoracic and mediastinal disorders           
Pulmonary embolism * 1  2/105 (1.90%)  0/77 (0.00%)  1/71 (1.41%)  2/178 (1.12%)  0/36 (0.00%) 
Interstitial lung disease * 1  1/105 (0.95%)  0/77 (0.00%)  0/71 (0.00%)  1/178 (0.56%)  0/36 (0.00%) 
Pneumonitis * 1  0/105 (0.00%)  0/77 (0.00%)  0/71 (0.00%)  2/178 (1.12%)  0/36 (0.00%) 
Pneumothorax * 1  0/105 (0.00%)  0/77 (0.00%)  0/71 (0.00%)  1/178 (0.56%)  1/36 (2.78%) 
Acute respiratory distress syndrome * 1  0/105 (0.00%)  1/77 (1.30%)  0/71 (0.00%)  0/178 (0.00%)  0/36 (0.00%) 
Cough * 1  1/105 (0.95%)  0/77 (0.00%)  0/71 (0.00%)  0/178 (0.00%)  0/36 (0.00%) 
Dyspnoea * 1  0/105 (0.00%)  0/77 (0.00%)  0/71 (0.00%)  1/178 (0.56%)  0/36 (0.00%) 
Lung disorder * 1  0/105 (0.00%)  0/77 (0.00%)  0/71 (0.00%)  1/178 (0.56%)  0/36 (0.00%) 
Lung infiltration * 1  1/105 (0.95%)  0/77 (0.00%)  0/71 (0.00%)  0/178 (0.00%)  0/36 (0.00%) 
Obliterative bronchiolitis * 1  0/105 (0.00%)  0/77 (0.00%)  0/71 (0.00%)  1/178 (0.56%)  0/36 (0.00%) 
Pleural effusion * 1  0/105 (0.00%)  0/77 (0.00%)  0/71 (0.00%)  1/178 (0.56%)  0/36 (0.00%) 
Acute respiratory failure * 1  1/105 (0.95%)  0/77 (0.00%)  0/71 (0.00%)  0/178 (0.00%)  0/36 (0.00%) 
Skin and subcutaneous tissue disorders           
Rash * 1  0/105 (0.00%)  0/77 (0.00%)  0/71 (0.00%)  0/178 (0.00%)  1/36 (2.78%) 
Skin oedema * 1  0/105 (0.00%)  0/77 (0.00%)  0/71 (0.00%)  1/178 (0.56%)  0/36 (0.00%) 
Surgical and medical procedures           
Central venous catheterisation * 1  0/105 (0.00%)  0/77 (0.00%)  1/71 (1.41%)  0/178 (0.00%)  0/36 (0.00%) 
Vascular disorders           
Deep vein thrombosis * 1  1/105 (0.95%)  1/77 (1.30%)  0/71 (0.00%)  2/178 (1.12%)  0/36 (0.00%) 
Thrombosis * 1  0/105 (0.00%)  1/77 (1.30%)  1/71 (1.41%)  0/178 (0.00%)  0/36 (0.00%) 
Axillary vein thrombosis * 1  0/105 (0.00%)  1/77 (1.30%)  0/71 (0.00%)  0/178 (0.00%)  0/36 (0.00%) 
Embolism venous * 1  1/105 (0.95%)  0/77 (0.00%)  0/71 (0.00%)  0/178 (0.00%)  0/36 (0.00%) 
Hypertension * 1  1/105 (0.95%)  0/77 (0.00%)  0/71 (0.00%)  0/178 (0.00%)  0/36 (0.00%) 
Hypotension * 1  0/105 (0.00%)  1/77 (1.30%)  0/71 (0.00%)  0/178 (0.00%)  0/36 (0.00%) 
Orthostatic hypotension * 1  0/105 (0.00%)  0/77 (0.00%)  0/71 (0.00%)  1/178 (0.56%)  0/36 (0.00%) 
Phlebitis * 1  0/105 (0.00%)  1/77 (1.30%)  0/71 (0.00%)  0/178 (0.00%)  0/36 (0.00%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA (14.0)
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
G+E: Rash ≥ Grade 2 G+E Standard Dose: Rash Grade < 2 G+E Escalating Dose: Rash Grade < 2 G+E: No Rash Non-Eligible G+E: Early Drop Out
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   105/105 (100.00%)   74/77 (96.10%)   71/71 (100.00%)   178/178 (100.00%)   34/36 (94.44%) 
Blood and lymphatic system disorders           
Thrombocytopenia * 1  47/105 (44.76%)  18/77 (23.38%)  15/71 (21.13%)  78/178 (43.82%)  8/36 (22.22%) 
Anaemia * 1  26/105 (24.76%)  26/77 (33.77%)  27/71 (38.03%)  66/178 (37.08%)  10/36 (27.78%) 
Neutropenia * 1  40/105 (38.10%)  20/77 (25.97%)  17/71 (23.94%)  75/178 (42.13%)  3/36 (8.33%) 
Leukopenia * 1  8/105 (7.62%)  7/77 (9.09%)  3/71 (4.23%)  29/178 (16.29%)  1/36 (2.78%) 
Gastrointestinal disorders           
Diarrhoea * 1  49/105 (46.67%)  33/77 (42.86%)  35/71 (49.30%)  71/178 (39.89%)  9/36 (25.00%) 
Nausea * 1  50/105 (47.62%)  28/77 (36.36%)  24/71 (33.80%)  69/178 (38.76%)  9/36 (25.00%) 
Vomiting * 1  27/105 (25.71%)  17/77 (22.08%)  23/71 (32.39%)  43/178 (24.16%)  8/36 (22.22%) 
Abdominal pain * 1  26/105 (24.76%)  13/77 (16.88%)  16/71 (22.54%)  49/178 (27.53%)  3/36 (8.33%) 
Constipation * 1  23/105 (21.90%)  11/77 (14.29%)  15/71 (21.13%)  35/178 (19.66%)  4/36 (11.11%) 
Abdominal pain upper * 1  10/105 (9.52%)  6/77 (7.79%)  5/71 (7.04%)  20/178 (11.24%)  3/36 (8.33%) 
Ascites * 1  3/105 (2.86%)  3/77 (3.90%)  2/71 (2.82%)  8/178 (4.49%)  3/36 (8.33%) 
Stomatitis * 1  10/105 (9.52%)  5/77 (6.49%)  7/71 (9.86%)  8/178 (4.49%)  2/36 (5.56%) 
Dyspepsia * 1  10/105 (9.52%)  3/77 (3.90%)  3/71 (4.23%)  9/178 (5.06%)  0/36 (0.00%) 
Abdominal distension * 1  4/105 (3.81%)  1/77 (1.30%)  5/71 (7.04%)  12/178 (6.74%)  0/36 (0.00%) 
General disorders           
Fatigue * 1  32/105 (30.48%)  17/77 (22.08%)  23/71 (32.39%)  53/178 (29.78%)  3/36 (8.33%) 
Pyrexia * 1  29/105 (27.62%)  22/77 (28.57%)  15/71 (21.13%)  44/178 (24.72%)  6/36 (16.67%) 
Asthenia * 1  10/105 (9.52%)  10/77 (12.99%)  12/71 (16.90%)  29/178 (16.29%)  6/36 (16.67%) 
Oedema peripheral * 1  15/105 (14.29%)  13/77 (16.88%)  6/71 (8.45%)  29/178 (16.29%)  1/36 (2.78%) 
Mucosal inflammation * 1  10/105 (9.52%)  8/77 (10.39%)  8/71 (11.27%)  15/178 (8.43%)  2/36 (5.56%) 
General physical health deterioration * 1  4/105 (3.81%)  2/77 (2.60%)  4/71 (5.63%)  2/178 (1.12%)  0/36 (0.00%) 
Influenza like illness * 1  7/105 (6.67%)  2/77 (2.60%)  2/71 (2.82%)  5/178 (2.81%)  0/36 (0.00%) 
Pain * 1  2/105 (1.90%)  4/77 (5.19%)  4/71 (5.63%)  3/178 (1.69%)  1/36 (2.78%) 
Hepatobiliary disorders           
Hyperbilirubinaemia * 1  2/105 (1.90%)  0/77 (0.00%)  1/71 (1.41%)  6/178 (3.37%)  3/36 (8.33%) 
Infections and infestations           
Urinary tract infection * 1  8/105 (7.62%)  2/77 (2.60%)  1/71 (1.41%)  13/178 (7.30%)  0/36 (0.00%) 
Investigations           
Weight decreased * 1  9/105 (8.57%)  7/77 (9.09%)  15/71 (21.13%)  22/178 (12.36%)  1/36 (2.78%) 
Alanine aminotransferase increased * 1  4/105 (3.81%)  6/77 (7.79%)  5/71 (7.04%)  7/178 (3.93%)  4/36 (11.11%) 
Aspartate aminotransferase increased * 1  5/105 (4.76%)  4/77 (5.19%)  2/71 (2.82%)  9/178 (5.06%)  3/36 (8.33%) 
Gamma-glutamyltransferase increased * 1  3/105 (2.86%)  5/77 (6.49%)  5/71 (7.04%)  7/178 (3.93%)  0/36 (0.00%) 
Blood alkaline phosphatase increased * 1  2/105 (1.90%)  4/77 (5.19%)  3/71 (4.23%)  5/178 (2.81%)  2/36 (5.56%) 
Metabolism and nutrition disorders           
Decreased appetite * 1  31/105 (29.52%)  17/77 (22.08%)  24/71 (33.80%)  52/178 (29.21%)  5/36 (13.89%) 
Hypokalaemia * 1  4/105 (3.81%)  4/77 (5.19%)  9/71 (12.68%)  10/178 (5.62%)  2/36 (5.56%) 
Musculoskeletal and connective tissue disorders           
Back pain * 1  9/105 (8.57%)  7/77 (9.09%)  10/71 (14.08%)  9/178 (5.06%)  0/36 (0.00%) 
Arthralgia * 1  2/105 (1.90%)  2/77 (2.60%)  1/71 (1.41%)  11/178 (6.18%)  0/36 (0.00%) 
Nervous system disorders           
Headache * 1  2/105 (1.90%)  8/77 (10.39%)  4/71 (5.63%)  6/178 (3.37%)  1/36 (2.78%) 
Dizziness * 1  5/105 (4.76%)  2/77 (2.60%)  5/71 (7.04%)  12/178 (6.74%)  1/36 (2.78%) 
Dysgeusia * 1  6/105 (5.71%)  4/77 (5.19%)  7/71 (9.86%)  7/178 (3.93%)  0/36 (0.00%) 
Psychiatric disorders           
Insomnia * 1  13/105 (12.38%)  8/77 (10.39%)  8/71 (11.27%)  14/178 (7.87%)  0/36 (0.00%) 
Depression * 1  5/105 (4.76%)  4/77 (5.19%)  2/71 (2.82%)  12/178 (6.74%)  1/36 (2.78%) 
Anxiety * 1  3/105 (2.86%)  4/77 (5.19%)  1/71 (1.41%)  5/178 (2.81%)  1/36 (2.78%) 
Respiratory, thoracic and mediastinal disorders           
Cough * 1  14/105 (13.33%)  7/77 (9.09%)  7/71 (9.86%)  20/178 (11.24%)  0/36 (0.00%) 
Dyspnoea * 1  15/105 (14.29%)  7/77 (9.09%)  3/71 (4.23%)  17/178 (9.55%)  3/36 (8.33%) 
Epistaxis * 1  3/105 (2.86%)  2/77 (2.60%)  4/71 (5.63%)  7/178 (3.93%)  0/36 (0.00%) 
Pleural effusion * 1  0/105 (0.00%)  1/77 (1.30%)  3/71 (4.23%)  0/178 (0.00%)  2/36 (5.56%) 
Skin and subcutaneous tissue disorders           
Rash * 1  105/105 (100.00%)  60/77 (77.92%)  64/71 (90.14%)  123/178 (69.10%)  19/36 (52.78%) 
Alopecia * 1  10/105 (9.52%)  7/77 (9.09%)  10/71 (14.08%)  23/178 (12.92%)  1/36 (2.78%) 
Dry skin * 1  9/105 (8.57%)  4/77 (5.19%)  13/71 (18.31%)  16/178 (8.99%)  1/36 (2.78%) 
Pruritus * 1  8/105 (7.62%)  2/77 (2.60%)  5/71 (7.04%)  12/178 (6.74%)  0/36 (0.00%) 
Palmar-plantar erythrodysaesthesia syndrome * 1  1/105 (0.95%)  1/77 (1.30%)  4/71 (5.63%)  3/178 (1.69%)  0/36 (0.00%) 
Vascular disorders           
Deep vein thrombosis * 1  3/105 (2.86%)  4/77 (5.19%)  3/71 (4.23%)  3/178 (1.69%)  2/36 (5.56%) 
Hypertension * 1  5/105 (4.76%)  5/77 (6.49%)  3/71 (4.23%)  5/178 (2.81%)  0/36 (0.00%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA (14.0)
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.
The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Medical Communications
Organization: Hoffman-LaRoche
Phone: 800-821-8590
EMail: genentech@druginfo.com
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Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT00652366     History of Changes
Other Study ID Numbers: BO21128
2007-003751-37
First Submitted: April 1, 2008
First Posted: April 3, 2008
Results First Submitted: December 8, 2014
Results First Posted: February 11, 2015
Last Update Posted: February 11, 2015