A Phase III Trial For Patients With Metastatic Breast Cancer

• 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: Eli Lilly and Company
• 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

Participant Flow

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
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. 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

Baseline Characteristics

Arm/Group Title		Gemcitabine Plus Docetaxel	Docetaxel Plus Capecitabine	Total
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 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
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

Outcome Measures

1. Primary Outcome

Title	Time to Disease Progression (Initial Treatment)
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)

Outcome Measure Data

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
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)

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)
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)

Outcome Measure Data

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
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)

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)
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)

Outcome Measure Data

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
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)

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)
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)

Outcome Measure Data

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
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)

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)
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)

Outcome Measure Data

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
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)

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)
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)

Outcome Measure Data

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
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)

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
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)

Outcome Measure Data

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
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)

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)
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)

Outcome Measure Data

Analysis Population Description

ITT population.

Arm/Group Title	Gemcitabine Plus Docetaxel	Docetaxel Plus Capecitabine
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

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)
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)

Outcome Measure Data

Analysis Population Description

Only included participants who crossed over from initial treatment to crossover treatment.

Arm/Group Title	Capecitabine	Gemcitabine
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

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)
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)

Outcome Measure Data

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
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)

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)
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)

Outcome Measure Data

Analysis Population Description

Participants with KPS at baseline (conclusion of initial treatment) and end of crossover treatment

Arm/Group Title	Capecitabine	Gemcitabine
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)

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)
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)

Outcome Measure Data

Analysis Population Description

Participants with RSCL at baseline and end of initial treatment.

Arm/Group Title	Gemcitabine Plus Docetaxel	Docetaxel Plus Capecitabine
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)

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)
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)

Outcome Measure Data

Analysis Population Description

Participants with RSCL at baseline (conclusion of initial treatment)and end of crossover treatment

Arm/Group Title	Capecitabine	Gemcitabine
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)

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]

Adverse Events

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
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	--/--		--/--
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
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

Limitations and Caveats

[Not Specified]

More Information

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