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A Phase III Trial For Patients With Metastatic Breast Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT00191152
Recruitment Status : Completed
First Posted : September 19, 2005
Results First Posted : December 8, 2009
Last Update Posted : December 24, 2009
Sponsor:
Information provided by:
Eli Lilly and Company

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Crossover Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Breast Cancer
Breast Neoplasms
Cancer of the Breast
Interventions Drug: gemcitabine
Drug: docetaxel
Drug: capecitabine
Enrollment 475
Recruitment Details  
Pre-assignment Details Not all participants who completed initial treatment went on to crossover treatment. Per protocol, participants had the option to go off study without receiving crossover treatment.
Arm/Group Title Gemcitabine Plus Docetaxel Docetaxel Plus Capecitabine
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Initial treatment: Gemcitabine 1000 milligrams per meter squared (mg/m2),intravenous (IV) on Days 1 and 8 every 21 days plus docetaxel 75 mg/m2 IV on Day 1 every 21 days. This treatment continues until progression of disease (PD), at which time crossover treatment begins.

Crossover treatment: capecitabine 1000 mg/m2 by mouth (PO) twice a day (BID), Days 1-14, every 21 days until PD at which time all treatment is discontinued. PD during crossover was defined as the Response Evaluation Criteria in Solid Tumors (RECIST) guideline with the tumor measurement at the start of crossover treatment (or end of initial treatment) considered as the crossover baseline, with subsequent tumor measurements during crossover treatment compared to the crossover baseline.

Initial treatment: Docetaxel 75 milligrams per meter squared (mg/m2), intravenous (IV) on Day 1 every 21 days plus capecitabine 1000 mg/m2, by mouth (PO), twice a day (BID), Days 1-14, every 21 days. This treatment continues until progression of disease (PD), at which time crossover treatment begins.

Crossover treatment: gemcitabine 1000 mg/m2, IV, Days 1 and 8, every 21 days. This treatment continues until PD at which time all treatment is discontinued.

Period Title: Initial Treatment
Started 239 236
Received Initial Treatment 236 227
Completed 98 83
Not Completed 141 153
Reason Not Completed
Adverse Event             43             67
Physician Decision             40             31
Withdrawal by Subject             40             28
Lost to Follow-up             0             6
not specified             18             21
Period Title: Crossover Treatment
Started 77 81
Received Treatment 76 80
Completed 50 53
Not Completed 27 28
Reason Not Completed
Adverse Event             8             8
Physician Decision             7             7
Withdrawal by Subject             6             9
Lost to Follow-up             2             1
Not Specified             4             3
Arm/Group Title Gemcitabine Plus Docetaxel Docetaxel Plus Capecitabine Total
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Initial treatment: Gemcitabine 1000 milligrams per meter squared (mg/m2), intravenous (IV) on Days 1 and 8 every 21 days plus docetaxel 75 mg/m2 IV on Day 1 every 21 days. This treatment continues until progression of disease (PD), at which time crossover treatment begins.

Crossover treatment: capecitabine 1000 mg/m2 by mouth (PO)twice a day (BID), Days 1-14, every 21 days until progressive disease (PD) at which time all treatment is discontinued.

Initial treatment: Docetaxel 75 milligrams per meter squared (mg/m2), intravenous (IV) on Day 1 every 21 days plus capecitabine 1000 mg/m2, by mouth (PO), twice a day (BID),Days 1-14, every 21 days. This treatment continues until progression of disease (PD), at which time crossover treatment begins.

Crossover treatment: gemcitabine 1000 mg/m2, IV, Days 1 and 8, every 21 days. This treatment continues until PD at which time all treatment is discontinued.

Total of all reporting groups
Overall Number of Baseline Participants 239 236 475
Hide Baseline Analysis Population Description
[Not Specified]
Age Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 239 participants 236 participants 475 participants
55.8  (11.77) 54.6  (11.60) 55.2  (11.69)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 239 participants 236 participants 475 participants
Female
237
  99.2%
1
   0.4%
238
  50.1%
Male
2
   0.8%
235
  99.6%
237
  49.9%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 239 participants 236 participants 475 participants
United States 173 166 339
Taiwan 15 18 33
Mexico 14 15 29
Puerto Rico 4 1 5
Argentina 11 13 24
Brazil 1 1 2
Australia 11 12 23
Korea, Republic of 10 10 20
Karnofsky Performance Status-Baseline   [1] 
Measure Type: Number
Unit of measure:  Units on a scale
Number Analyzed 239 participants 236 participants 475 participants
<=60 Needs increasing assistance up to Death (0) 0 0 0
70 - Unable to carry on normal activity 16 15 31
80 - Activity with effort; some signs of disease 44 40 84
90 - Normal activity; minor signs of disease 101 101 202
100 - Normal no complaints; no evidence of disease 74 75 149
Missing 4 5 9
[1]
Measure Description: Classifies patients according to their functional impairment. Scores range from 0-100, the lower the score, the worse the survival for most serious illnesses.
Race/Ethnicity  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 239 participants 236 participants 475 participants
Caucasian 160 158 318
African Descent 23 12 35
Oriental 28 30 58
Hispanic 26 36 62
Other 2 0 2
1.Primary Outcome
Title Time to Disease Progression (Initial Treatment)
Hide Description Time to disease progression (TTDP) at initial treatment was defined as the number of months between date of randomization and the date of first documented disease progression or the date of death due to disease under study, whichever came first. TTDP censored at earliest of: 1) date of death not due to disease; or 2) date of last contact for participants alive without disease progression; or 3) start date of other anti-tumor therapy; or 4) first dose date of crossover treatment.
Time Frame Randomization date to the earliest date of first documented disease progression date or the date of death if the participant died due to study disease (up to 82 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat (ITT) population: all randomized participants. Censored participants in initial treatment: 68 gemcitabine/docetaxel arm; 83 docetaxel/capecitabine arm.
Arm/Group Title Gemcitabine Plus Docetaxel Docetaxel Plus Capecitabine
Hide Arm/Group Description:

gemcitabine 1000 milligrams per meter squared (mg/m2) intravenous, days 1 and 8 every 21 days plus docetaxel 75 mg/m2, intravenous, day 1 every 21 days.

Treatment continues until progression of disease at which time crossover treatment begins.

docetaxel 75 mg/m2, intravenous, day 1 every 21 days plus capecitabine 1000 mg/m2, by mouth twice a day, days 1-14 every 21 days. Treatment continues until progression of disease, at which time crossover treatment begins.
Overall Number of Participants Analyzed 239 236
Median (95% Confidence Interval)
Unit of Measure: months
9.28
(7.73 to 10.79)
8.88
(7.37 to 11.05)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Gemcitabine Plus Docetaxel, Docetaxel Plus Capecitabine
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.385
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
2.Secondary Outcome
Title Time to Disease Progression (Crossover Treatment)
Hide Description For crossover treatment, time to disease progression (TTDP) was defined as the number of months between the first dose date of crossover treatment and the date of disease progression or the date of death due to disease under study, whichever came first. TTDP for crossover treatment only applied to those participants who crossed over from initial treatment to crossover treatment. TTDP censored at earliest of: 1)date of death not due to disease; or 2)date of last contact for participants alive without disease progression; or 3)start date of other anti-tumor therapy due to progression.
Time Frame Date of first dose of crossover treatment to date of first-documented disease progression after receiving first crossover treatment or date of death due to study disease, whichever came first (up to 82 months)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population: all randomized participants. Censored participants in crossover treatment: 13 in capecitabine arm; 10 in gemcitabine arm.
Arm/Group Title Capecitabine Gemcitabine
Hide Arm/Group Description:
capecitabine 1000 mg/m2, by mouth two times per day, days 1-14 every 21 days until progression of disease at which time all treatment is discontinued.
gemcitabine 1000 mg/m2, intravenous, days 1 and 8 every 21 days until progression of disease at which time all treatment is discontinued.
Overall Number of Participants Analyzed 77 81
Median (95% Confidence Interval)
Unit of Measure: months
4.51
(2.11 to 7.80)
2.34
(2.04 to 3.78)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Capecitabine, Gemcitabine
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.145
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
3.Secondary Outcome
Title Progression-Free Survival (Initial Treatment)
Hide Description For initial treatment, progression-free survival (PFS) was defined as the number of months between the date of randomization and the date of first documented disease progression or the date of death due to any cause, whichever came first. Time to PFS was censored at the earliest of: 1) date of last contact for participants alive without disease progression; or 2) start date of other anti-tumor therapy for progression; or 3) first dose date of crossover treatment.
Time Frame Date of randomization until the date of first documented progression or date of death from any cause, whichever came first (up to 82 months)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT: all randomized participants. Censored participants (initial treatment): 64 in gemcitabine/docetaxel arm; 80 in docetaxel/capecitabine arm.
Arm/Group Title Gemcitabine Plus Docetaxel Docetaxel Plus Capecitabine
Hide Arm/Group Description:
gemcitabine 1000 mg/m2, intravenous on days 1 and 8 every 21 days plus docetaxel 75 mg/m2 intravenous on day 1 every 21 days. This treatment continues until progression of disease at which time crossover treatment begins.
docetaxel 75 mg/m2, intravenous, on day 1 every 21 days plus capecitabine 1000 mg/m2, by mouth twice a day, days 1-14, every 21 days. This treatment continues until progression of disease at which time crossover treatment begins.
Overall Number of Participants Analyzed 239 236
Median (95% Confidence Interval)
Unit of Measure: months
9.01
(7.73 to 10.53)
8.88
(7.27 to 10.89)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Gemcitabine Plus Docetaxel, Docetaxel Plus Capecitabine
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.361
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
4.Secondary Outcome
Title Progression-Free Survival (Crossover Treatment)
Hide Description For crossover treatment, progression-free survival (PFS) was defined as the number of months between first dose date of crossover treatment and date of documented disease progression or date of death due to any cause, whichever came first. PFS for crossover treatment only applied to those participants who crossed over from initial treatment to crossover treatment. PFS was censored at the earliest of: 1) date of last contact for participants alive without disease progression; or 2) start date of other anti-tumor therapy for participants with documented disease progression.
Time Frame First dose date of crossover treatment to date of first-documented progression after receiving crossover treatment or date of death due to any cause, whichever came first (up to 82 months)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population: all randomized participants. Censored participants, crossover treatment: 13 in capecitabine arm; 10 in gemcitabine arm.
Arm/Group Title Capecitabine Gemcitabine
Hide Arm/Group Description:
capecitabine 1000 mg/m2, by mouth two times per day, days 1-14 every 21 days until progression of disease at which time all treatment is discontinued.
gemcitabine 1000 mg/m2, intravenous, days 1 and 8 every 21 days until progression of disease at which time all treatment is discontinued.
Overall Number of Participants Analyzed 77 81
Median (95% Confidence Interval)
Unit of Measure: months
4.51
(2.11 to 7.80)
2.34
(2.04 to 3.78)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Capecitabine, Gemcitabine
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.145
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
5.Secondary Outcome
Title Duration of Response (Initial Treatment)
Hide Description Among tumor responders, duration of tumor response was measured from the date of response (complete response [CR] or partial response [PR] until the first date of documented progression or death from any cause. Duration of response was censored at the earliest of: 1) date of last contact for participants alive without disease progression (DP); or 2) start date of other anti-tumor therapy for DP; or 3) dose date of crossover treatment.
Time Frame Date of response (CR or PR) until the first date of documented progression or death from any cause (up to 82 months)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population: participants with CR or PR as best overall response (initial treatment). Censored participants: 16 in gemcitabine/docetaxel arm; 30 in docetaxel/capecitabine arm.
Arm/Group Title Gemcitabine Plus Docetaxel Docetaxel Plus Capecitabine
Hide Arm/Group Description:
gemcitabine 1000 mg/m2, intravenous on days 1 and 8 every 21 days plus docetaxel 75 mg/m2 intravenous on day 1 every 21 days. This treatment continues until progression of disease at which time crossover treatment begins.
docetaxel 75 mg/m2, intravenous, on day 1 every 21 days plus capecitabine 1000 mg/m2, by mouth twice a day, days 1-14, every 21 days. This treatment continues until progression of disease at which time crossover treatment begins.
Overall Number of Participants Analyzed 77 85
Median (95% Confidence Interval)
Unit of Measure: months
9.11
(7.60 to 11.94)
10.39
(8.22 to 13.75)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Gemcitabine Plus Docetaxel, Docetaxel Plus Capecitabine
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.377
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
6.Secondary Outcome
Title Duration of Response (Crossover Treatment)
Hide Description At crossover treatment, duration of response was measured from the time criteria were met for complete response (CR) or partial response (PR), until first date that recurrent or progressive disease was objectively documented or date of death due to any cause, whichever came first. This definition only applied to those who crossed over & achieved CR or PR in crossover treatment. Duration of response censored at earliest of: 1) date of last contact for those alive without disease progression; or 2) start date of other anti-tumor therapy for documented disease progression.
Time Frame Date of CR or PR until first date of recurrent or progressive disease after receiving crossover treatment was objectively documented or date of date due to any cause, whichever came first (up to 82 months)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population: participants with CR or PR as best overall response at crossover treatment. Censored participants: 4 in capecitabine arm; 2 in gemcitabine arm.
Arm/Group Title Capecitabine Gemcitabine
Hide Arm/Group Description:
capecitabine 1000 mg/m2, by mouth two times per day, days 1-14 every 21 days until progression of disease at which time all treatment is discontinued.
gemcitabine 1000 mg/m2, intravenous, days 1 and 8 every 21 days until progression of disease at which time all treatment is discontinued.
Overall Number of Participants Analyzed 11 7
Median (95% Confidence Interval)
Unit of Measure: months
25.89
(4.64 to 45.03)
42.50
(16.02 to 48.22)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Capecitabine, Gemcitabine
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.446
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
7.Secondary Outcome
Title Overall Survival
Hide Description Overall survival time was defined as the number of months between the date of randomization and the date of death due to any cause. The overall survival time was censored at the date of last contact for participants who were still alive.
Time Frame Date of randomization to date of death from any cause (up to 82 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Intent to treat population: all randomized participant. Censored participants: 75 in gemcitabine/docetaxel arm; 72 in docetaxel/capecitabine arm.
Arm/Group Title Gemcitabine Plus Docetaxel Docetaxel Plus Capecitabine
Hide Arm/Group Description:
gemcitabine 1000 mg/m2, intravenous, days 1 and 8 every 21 days plus docetaxel 75 mg/m2, intravenous, day 1 every 21 days. Treatment continues until progression of disease at which time crossover treatment begins.
docetaxel 75 mg/m2, intravenous, day 1 every 21 days plus capecitabine 1000 mg/m2, by mouth twice a day, days 1-14 every 21 days. Treatment continues until progression of disease at which time crossover treatment begins.
Overall Number of Participants Analyzed 239 236
Median (95% Confidence Interval)
Unit of Measure: months
22.99
(18.82 to 25.69)
23.29
(18.55 to 25.53)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Gemcitabine Plus Docetaxel, Docetaxel Plus Capecitabine
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.785
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
8.Secondary Outcome
Title Best Overall Response (Initial Treatment)
Hide Description Best overall response was the best response recorded from the start of the treatment until disease progression/recurrence (taking as reference for progressive disease the smallest measurements recorded since the treatment started). Response was assessed using Response Evaluation Criteria In Solid Tumors (RECIST) criteria. Complete Response=disappearance of all target lesions; Partial Response=30% decrease in sum of longest diameter of target lesions; Progressive Disease=20% increase in sum of longest diameter of target lesions; Stable Disease=small changes that did not meet above criteria.
Time Frame Best response from start of treatment until disease progression/recurrence (up to 82 months)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population.
Arm/Group Title Gemcitabine Plus Docetaxel Docetaxel Plus Capecitabine
Hide Arm/Group Description:
gemcitabine 1000 mg/m2, intravenous, days 1 and 8 every 21 days plus docetaxel 75 mg/m2, intravenous, day 1 every 21 days. Treatment continues until progression of disease at which time crossover treatment begins.
docetaxel 75 mg/m2, intravenous, day 1 every 21 days plus capecitabine 1000 mg/m2, by mouth twice a day, days 1-14, every 21 days. Treatment continues until progression of disease at which time crossover treatment begins.
Overall Number of Participants Analyzed 239 236
Measure Type: Number
Unit of Measure: participants
Complete Response (confirmed) 6 6
Partial Response (confirmed) 71 79
Stable Disease 96 90
Progressive Disease 32 27
Unknown 34 34
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Gemcitabine Plus Docetaxel, Docetaxel Plus Capecitabine
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.364
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
9.Secondary Outcome
Title Best Overall Response (Crossover Treatment)
Hide Description Best overall response was the best response recorded from the start of treatment until disease progression/recurrence (taking as reference for progressive disease the smallest measurements recorded since the treatment started). Response assessed using RECIST criteria. Complete Response=disappearance of all target lesions; Partial Response=30% decrease in sum of longest diameter of target lesions; Progressive Disease=20% increase in sum of longest diameter of target lesions; Stable Disease=small changes that did not meet above criteria.
Time Frame Best response from start of treatment until disease progression/recurrence (up to 82 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Only included participants who crossed over from initial treatment to crossover treatment.
Arm/Group Title Capecitabine Gemcitabine
Hide Arm/Group Description:
capecitabine 1000 mg/m2, by mouth two times per day, days 1-14 every 21 days until progression of disease at which time all treatment is discontinued.
gemcitabine 1000 mg/m2, intravenous, days 1 and 8 every 21 days until progression of disease at which time all treatment is discontinued.
Overall Number of Participants Analyzed 77 81
Measure Type: Number
Unit of Measure: participants
Complete Response (confirmed) 1 1
Partial Response (confirmed) 10 6
Stable Disease 19 20
Progressive Disease 34 36
Unknown 13 18
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Capecitabine, Gemcitabine
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.446
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
10.Secondary Outcome
Title Summary of Changes in Karnofsky Performance Status (KPS) by Treatment (Initial Treatment)
Hide Description KPS ranges from 0 to 100, subdivided into three categories: incapacitated (0-40), self-care (50-70), and normal activity (80-100).
Time Frame Baseline until crossover treatment began (up to 82 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat population, initial treatment, participants with KPS at baseline and end of initial treatment.
Arm/Group Title Gemcitabine Plus Docetaxel Docetaxel Plus Capecitabine
Hide Arm/Group Description:
gemcitabine 1000 mg/m2, intravenous, days 1 and 8 every 21 days plus docetaxel 75 mg/m2, intravenous, day 1 every 21 days. Treatment continues until progression of disease at which time crossover treatment begins.
docetaxel 75 mg/m2, intravenous, day 1 every 21 days plus capecitabine 1000 mg/m2, by mouth twice a day, days 1-14, every 21 days. Treatment continues until progression of disease at which time crossover treatment begins.
Overall Number of Participants Analyzed 212 214
Mean (Standard Deviation)
Unit of Measure: units on a scale
Baseline 90.85  (8.159) 90.09  (8.335)
Change from Baseline -3.30  (9.259) -3.27  (9.118)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Gemcitabine Plus Docetaxel, Docetaxel Plus Capecitabine
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.990
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
11.Secondary Outcome
Title Summary of Changes in Karnofsky Performance Status (KPS) by Treatment (Crossover Treatment)
Hide Description KPS ranges from 0 to 100, subdivided into three categories: incapacitated (0-40), self-care (50-70), and normal activity (80-100).
Time Frame First day of crossover treatment until end of crossover treatment at trial discontinuation (up to 82 moths)
Hide Outcome Measure Data
Hide Analysis Population Description
Participants with KPS at baseline (conclusion of initial treatment) and end of crossover treatment
Arm/Group Title Capecitabine Gemcitabine
Hide Arm/Group Description:
capecitabine 1000 mg/m2, by mouth two times per day, days 1-14, every 21 days
gemcitabine 1000 mg/m2 intravenously, days 1 and 8, every 21 days
Overall Number of Participants Analyzed 66 63
Mean (Standard Deviation)
Unit of Measure: units on a scale
Baseline 89.09  (7.174) 87.94  (9.360)
Change from Baseline -0.30  (7.839) -1.27  (9.068)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Capecitabine, Gemcitabine
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.117
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
12.Secondary Outcome
Title Summary of Changes in Rotterdam Symptom Checklist (RSCL) by Treatment (Initial Treatment)
Hide Description RSCL includes 4 scales to assess quality of life (QOL) endpoints: 1) a 23-item physical distress level with scale score ranges from 23 to 92 [low score represents better QOL] 2)a 7-item psychological distress level with scale score ranges from 7 to 28[low score represents better QOL] 3)8-item activity level with scale score ranges from 8 to 32 [high score represents better QOL]; 1-item overall valuation of life with score range from 1 to 7 [low score represents better QOL].
Time Frame Baseline until crossover treatment began (up to 82 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Participants with RSCL at baseline and end of initial treatment.
Arm/Group Title Gemcitabine Plus Docetaxel Docetaxel Plus Capecitabine
Hide Arm/Group Description:
gemcitabine 1000 mg/m2, intravenous, on Days 1 and 8 every 21 days plus docetaxel 75 mg/m2, intravenous, on Day 1 every 21 days. This treatment continues until progression of disease at which time crossover treatment begins.
docetaxel 75 mg/m2, intravenous on Day 1 every 21 days plus capecitabine 1000 mg/m2, by mouth, twice a day, days 1-14, every 21 days. This treatment continues until progression of disease at which time crossover treatment begins.
Overall Number of Participants Analyzed 117 118
Mean (Standard Deviation)
Unit of Measure: units on a scale
Baseline 68.09  (25.103) 72.32  (23.693)
Change from Baseline 2.42  (27.093) -2.68  (26.685)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Gemcitabine Plus Docetaxel, Docetaxel Plus Capecitabine
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.801
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
13.Secondary Outcome
Title Summary of Changes in Rotterdam Symptom Checklist by Treatment (Crossover Treatment)
Hide Description RSCL includes 4 scales to assess quality of life (QOL) endpoints: 1) a 23-item physical distress level with scale score ranges from 23 to 92 [low score represents better QOL] 2)a 7-item psychological distress level with scale score ranges from 7 to 28[low score represents better QOL] 3)8-item activity level with scale score ranges from 8 to 32 [high score represents better QOL]; 1-item overall valuation of life with score range from 1 to 7 [low score represents better QOL].
Time Frame First day of crossover treatment until end of crossover treatment at trial discontinuation (up to 82 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Participants with RSCL at baseline (conclusion of initial treatment)and end of crossover treatment
Arm/Group Title Capecitabine Gemcitabine
Hide Arm/Group Description:
capecitabine 1000 mg/m2, by mouth twice day, days 1-14 every 21 days until progression of disease at which time all treatment is discontinued.
gemcitabine 1000 mg/m2, intravenous, days 1 and 8 every 21 days until progression of disease at which time all treatment is discontinued.
Overall Number of Participants Analyzed 30 24
Mean (Standard Deviation)
Unit of Measure: units on a scale
Baseline 75.00  (20.876) 76.39  (17.663)
Change from Baseline -2.78  (21.029) -0.69  (27.133)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Capecitabine, Gemcitabine
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.190
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Time Frame [Not Specified]
Adverse Event Reporting Description A participant was randomized to comparator arm but treated with experimental treatment and thus included in the comparator arm ITT population (disposition and efficacy tables) and included in the experimental arm of treated population (AE tables). This results in an inconsistency between number of participants analysed and participant flow module.
 
Arm/Group Title Gemcitabine Plus Docetaxel Docetaxel Plus Capecitabine
Hide Arm/Group Description

Initial treatment: Gemcitabine 1000 milligrams per meter squared (mg/m2), intravenous (IV) on Days 1 and 8 every 21 days plus docetaxel 75 mg/m2 IV on Day 1 every 21 days. This treatment continues until progression of disease (PD), at which time crossover treatment begins.

Crossover treatment: capecitabine 1000 mg/m2 by mouth (PO) twice a day (BID), Days 1-14, every 21 days until PD at which time all treatment is discontinued.

Initial treatment: Docetaxel 75 milligrams per meter squared (mg/m2), intravenous (IV) on Day 1 every 21 days plus capecitabine 1000 mg/m2, by mouth (PO), twice a day (BID), Days 1-14, every 21 days. This treatment continues until progression of disease (PD), at which time crossover treatment begins.

Crossover treatment: gemcitabine 1000 mg/m2, IV, Days 1 and 8, every 21 days. This treatment continues until PD at which time all treatment is discontinued.

All-Cause Mortality
Gemcitabine Plus Docetaxel Docetaxel Plus Capecitabine
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Gemcitabine Plus Docetaxel Docetaxel Plus Capecitabine
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   72/237 (30.38%)      55/226 (24.34%)    
Blood and lymphatic system disorders     
Anaemia  1  2/237 (0.84%)  2 1/226 (0.44%)  1
Disseminated intravascular coagulation  1  1/237 (0.42%)  1 0/226 (0.00%)  0
Febrile neutropenia  1  9/237 (3.80%)  10 9/226 (3.98%)  9
Leukocytosis  1  1/237 (0.42%)  1 0/226 (0.00%)  0
Leukopenia  1  6/237 (2.53%)  9 2/226 (0.88%)  3
Lymphopenia  1  1/237 (0.42%)  1 0/226 (0.00%)  0
Neutropenia  1  25/237 (10.55%)  38 7/226 (3.10%)  11
Thrombocytopenia  1  2/237 (0.84%)  2 0/226 (0.00%)  0
Cardiac disorders     
Atrial fibrillation  1  0/237 (0.00%)  0 1/226 (0.44%)  1
Cardiac failure congestive  1  2/237 (0.84%)  2 0/226 (0.00%)  0
Cardiac tamponade  1  1/237 (0.42%)  1 0/226 (0.00%)  0
Cardiopulmonary failure  1  1/237 (0.42%)  1 0/226 (0.00%)  0
Pericardial effusion  1  4/237 (1.69%)  4 0/226 (0.00%)  0
Tachycardia  1  1/237 (0.42%)  1 0/226 (0.00%)  0
Gastrointestinal disorders     
Abdominal pain  1  2/237 (0.84%)  2 0/226 (0.00%)  0
Diarrhoea  1  2/237 (0.84%)  2 4/226 (1.77%)  4
Diverticulitis  1  1/237 (0.42%)  2 0/226 (0.00%)  0
Enterocolitis  1  0/237 (0.00%)  0 1/226 (0.44%)  1
Gastrointestinal haemorrhage  1  0/237 (0.00%)  0 1/226 (0.44%)  1
Intestinal perforation  1  0/237 (0.00%)  0 1/226 (0.44%)  1
Nausea  1  2/237 (0.84%)  2 2/226 (0.88%)  2
Oesophagitis  1  0/237 (0.00%)  0 1/226 (0.44%)  1
Pancreatitis  1  1/237 (0.42%)  1 0/226 (0.00%)  0
Ruptured diverticulum  1  1/237 (0.42%)  1 0/226 (0.00%)  0
Volvulus of bowel  1  0/237 (0.00%)  0 1/226 (0.44%)  1
Vomiting  1  4/237 (1.69%)  4 3/226 (1.33%)  3
General disorders     
Asthenia  1  0/237 (0.00%)  0 1/226 (0.44%)  1
Catheter site erythema  1  1/237 (0.42%)  1 0/226 (0.00%)  0
Chest pain  1  0/237 (0.00%)  0 1/226 (0.44%)  1
Fatigue  1  3/237 (1.27%)  3 2/226 (0.88%)  2
Lethargy  1  1/237 (0.42%)  1 0/226 (0.00%)  0
Malaise  1  0/237 (0.00%)  0 1/226 (0.44%)  1
Mucosal inflammation  1  1/237 (0.42%)  1 0/226 (0.00%)  0
Multi-organ failure  1  1/237 (0.42%)  1 0/226 (0.00%)  0
Oedema peripheral  1  1/237 (0.42%)  1 0/226 (0.00%)  0
Pyrexia  1  4/237 (1.69%)  4 5/226 (2.21%)  5
Infections and infestations     
Bronchopneumonia  1  1/237 (0.42%)  1 0/226 (0.00%)  0
Catheter related infection  1  0/237 (0.00%)  0 1/226 (0.44%)  1
Catheter sepsis  1  1/237 (0.42%)  1 0/226 (0.00%)  0
Catheter site infection  1  2/237 (0.84%)  2 0/226 (0.00%)  0
Cellulitis  1  0/237 (0.00%)  0 3/226 (1.33%)  3
Cellulitis orbital  1  0/237 (0.00%)  0 1/226 (0.44%)  1
Clostridium colitis  1  2/237 (0.84%)  2 0/226 (0.00%)  0
Escherichia infection  1  1/237 (0.42%)  1 0/226 (0.00%)  0
Infection  1  1/237 (0.42%)  1 3/226 (1.33%)  3
Lobar pneumonia  1  1/237 (0.42%)  1 0/226 (0.00%)  0
Neutropenic sepsis  1  2/237 (0.84%)  2 0/226 (0.00%)  0
Periorbital cellulitis  1  0/237 (0.00%)  0 1/226 (0.44%)  1
Pneumonia  1  3/237 (1.27%)  3 3/226 (1.33%)  3
Pyelonephritis  1  1/237 (0.42%)  1 0/226 (0.00%)  0
Sepsis  1  2/237 (0.84%)  2 0/226 (0.00%)  0
Septic shock  1  2/237 (0.84%)  2 0/226 (0.00%)  0
Urinary tract infection  1  2/237 (0.84%)  2 1/226 (0.44%)  1
Urosepsis  1  1/237 (0.42%)  1 0/226 (0.00%)  0
Injury, poisoning and procedural complications     
Seroma  1  0/237 (0.00%)  0 1/226 (0.44%)  1
Investigations     
Blood alkaline phosphatase increased  1  1/237 (0.42%)  1 0/226 (0.00%)  0
Haematocrit decreased  1  1/237 (0.42%)  1 1/226 (0.44%)  1
Metabolism and nutrition disorders     
Anorexia  1  2/237 (0.84%)  2 2/226 (0.88%)  2
Dehydration  1  4/237 (1.69%)  4 2/226 (0.88%)  2
Failure to thrive  1  0/237 (0.00%)  0 1/226 (0.44%)  1
Hyperglycaemia  1  0/237 (0.00%)  0 1/226 (0.44%)  1
Musculoskeletal and connective tissue disorders     
Chest wall pain  1  0/237 (0.00%)  0 1/226 (0.44%)  1
Neck pain  1  0/237 (0.00%)  0 1/226 (0.44%)  1
Pain in extremity  1  1/237 (0.42%)  1 0/226 (0.00%)  0
Nervous system disorders     
Cerebral haemorrhage  1  0/237 (0.00%)  0 1/226 (0.44%)  1
Peripheral sensory neuropathy  1  1/237 (0.42%)  1 1/226 (0.44%)  1
Renal and urinary disorders     
Bilateral hydronephrosis  1  1/237 (0.42%)  1 0/226 (0.00%)  0
Renal insufficiency  1  3/237 (1.27%)  3 0/226 (0.00%)  0
Renal tubular necrosis  1  1/237 (0.42%)  1 0/226 (0.00%)  0
Reproductive system and breast disorders     
Breast pain  1  0/237 (0.00%)  0 1/226 (0.44%)  1
Respiratory, thoracic and mediastinal disorders     
Acute respiratory distress syndrome  1  1/237 (0.42%)  1 0/226 (0.00%)  0
Chronic obstructive airways disease exacerbated  1  1/237 (0.42%)  3 0/226 (0.00%)  0
Dyspnoea  1  4/237 (1.69%)  4 2/226 (0.88%)  2
Dyspnoea exacerbated  1  1/237 (0.42%)  1 0/226 (0.00%)  0
Hypoxia  1  0/237 (0.00%)  0 2/226 (0.88%)  2
Lung infiltration  1  1/237 (0.42%)  1 1/226 (0.44%)  1
Orthopnoea  1  1/237 (0.42%)  1 0/226 (0.00%)  0
Pleural effusion  1  3/237 (1.27%)  3 1/226 (0.44%)  1
Pulmonary embolism  1  5/237 (2.11%)  5 0/226 (0.00%)  0
Tachypnoea  1  1/237 (0.42%)  1 0/226 (0.00%)  0
Skin and subcutaneous tissue disorders     
Alopecia  1  0/237 (0.00%)  0 1/226 (0.44%)  1
Palmar-plantar erythrodysaesthesia syndrome  1  0/237 (0.00%)  0 4/226 (1.77%)  4
Skin ulcer  1  0/237 (0.00%)  0 1/226 (0.44%)  1
Vascular disorders     
Deep vein thrombosis  1  1/237 (0.42%)  1 2/226 (0.88%)  2
Embolism  1  1/237 (0.42%)  1 0/226 (0.00%)  0
Hypotension  1  0/237 (0.00%)  0 1/226 (0.44%)  1
Jugular vein thrombosis  1  0/237 (0.00%)  0 1/226 (0.44%)  1
Phlebothrombosis  1  1/237 (0.42%)  1 0/226 (0.00%)  0
Shock  1  1/237 (0.42%)  1 0/226 (0.00%)  0
Subclavian vein thrombosis  1  0/237 (0.00%)  0 1/226 (0.44%)  1
Thrombophlebitis  1  1/237 (0.42%)  1 0/226 (0.00%)  0
Thrombosis  1  0/237 (0.00%)  0 2/226 (0.88%)  2
Venous occlusion  1  1/237 (0.42%)  1 0/226 (0.00%)  0
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 11.0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Gemcitabine Plus Docetaxel Docetaxel Plus Capecitabine
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   233/237 (98.31%)      221/226 (97.79%)    
Blood and lymphatic system disorders     
Anaemia  1  113/237 (47.68%)  278 59/226 (26.11%)  110
Leukopenia  1  86/237 (36.29%)  294 25/226 (11.06%)  53
Neutropenia  1  193/237 (81.43%)  883 73/226 (32.30%)  216
Thrombocytopenia  1  70/237 (29.54%)  152 6/226 (2.65%)  13
Eye disorders     
Lacrimation increased  1  15/237 (6.33%)  23 29/226 (12.83%)  38
Gastrointestinal disorders     
Abdominal pain  1  33/237 (13.92%)  42 30/226 (13.27%)  43
Constipation  1  65/237 (27.43%)  100 49/226 (21.68%)  71
Diarrhoea  1  111/237 (46.84%)  217 108/226 (47.79%)  221
Dyspepsia  1  21/237 (8.86%)  28 28/226 (12.39%)  44
Nausea  1  113/237 (47.68%)  233 118/226 (52.21%)  248
Stomatitis  1  47/237 (19.83%)  92 60/226 (26.55%)  113
Vomiting  1  71/237 (29.96%)  120 74/226 (32.74%)  134
General disorders     
Asthenia  1  45/237 (18.99%)  104 32/226 (14.16%)  61
Chest pain  1  15/237 (6.33%)  23 12/226 (5.31%)  13
Fatigue  1  129/237 (54.43%)  285 120/226 (53.10%)  224
Mucosal inflammation  1  38/237 (16.03%)  81 65/226 (28.76%)  117
Oedema  1  31/237 (13.08%)  77 27/226 (11.95%)  46
Oedema peripheral  1  54/237 (22.78%)  90 44/226 (19.47%)  67
Pain  1  25/237 (10.55%)  45 18/226 (7.96%)  31
Pyrexia  1  60/237 (25.32%)  93 33/226 (14.60%)  38
Rigors  1  15/237 (6.33%)  22 9/226 (3.98%)  9
Infections and infestations     
Candidiasis  1  5/237 (2.11%)  9 12/226 (5.31%)  14
Upper respiratory tract infection  1  17/237 (7.17%)  21 8/226 (3.54%)  8
Urinary tract infection  1  13/237 (5.49%)  19 11/226 (4.87%)  11
Investigations     
Alanine aminotransferase increased  1  28/237 (11.81%)  42 13/226 (5.75%)  19
Aspartate aminotransferase increased  1  21/237 (8.86%)  31 14/226 (6.19%)  22
Weight decreased  1  16/237 (6.75%)  23 10/226 (4.42%)  14
Metabolism and nutrition disorders     
Anorexia  1  59/237 (24.89%)  122 59/226 (26.11%)  92
Dehydration  1  21/237 (8.86%)  24 22/226 (9.73%)  26
Hyperglycaemia  1  21/237 (8.86%)  47 15/226 (6.64%)  21
Hypocalcaemia  1  10/237 (4.22%)  22 12/226 (5.31%)  17
Hypokalaemia  1  13/237 (5.49%)  16 14/226 (6.19%)  17
Musculoskeletal and connective tissue disorders     
Arthralgia  1  43/237 (18.14%)  60 39/226 (17.26%)  62
Back pain  1  24/237 (10.13%)  34 23/226 (10.18%)  31
Bone pain  1  21/237 (8.86%)  29 10/226 (4.42%)  12
Myalgia  1  46/237 (19.41%)  105 33/226 (14.60%)  62
Pain in extremity  1  25/237 (10.55%)  42 25/226 (11.06%)  31
Nervous system disorders     
Dizziness  1  21/237 (8.86%)  24 19/226 (8.41%)  32
Dysgeusia  1  32/237 (13.50%)  50 29/226 (12.83%)  39
Headache  1  41/237 (17.30%)  53 32/226 (14.16%)  38
Peripheral sensory neuropathy  1  78/237 (32.91%)  133 83/226 (36.73%)  141
Psychiatric disorders     
Depression  1  16/237 (6.75%)  21 9/226 (3.98%)  10
Insomnia  1  31/237 (13.08%)  38 30/226 (13.27%)  37
Respiratory, thoracic and mediastinal disorders     
Cough  1  54/237 (22.78%)  92 45/226 (19.91%)  55
Dyspnoea  1  55/237 (23.21%)  81 37/226 (16.37%)  51
Pharyngolaryngeal pain  1  20/237 (8.44%)  26 11/226 (4.87%)  17
Skin and subcutaneous tissue disorders     
Alopecia  1  86/237 (36.29%)  120 98/226 (43.36%)  127
Erythema  1  10/237 (4.22%)  10 15/226 (6.64%)  19
Nail disorder  1  38/237 (16.03%)  70 67/226 (29.65%)  118
Palmar-plantar erythrodysaesthesia syndrome  1  15/237 (6.33%)  20 129/226 (57.08%)  370
Pruritus  1  14/237 (5.91%)  16 10/226 (4.42%)  11
Rash  1  59/237 (24.89%)  82 32/226 (14.16%)  44
Vascular disorders     
Hypotension  1  12/237 (5.06%)  13 6/226 (2.65%)  6
Lymphoedema  1  14/237 (5.91%)  24 10/226 (4.42%)  12
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 11.0
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.
Results Point of Contact
Name/Title: Chief Medical Officer
Organization: Eli Lilly and Company
Phone: 1-800-545-5979
Responsible Party: Chief Medical Officer, Eli Lilly
ClinicalTrials.gov Identifier: NCT00191152     History of Changes
Other Study ID Numbers: 4703
B9E-US-S188
First Submitted: September 12, 2005
First Posted: September 19, 2005
Results First Submitted: November 4, 2009
Results First Posted: December 8, 2009
Last Update Posted: December 24, 2009