A Phase III Trial For Patients With Metastatic Breast Cancer

Phase 3

Completed

• Conditions: Breast Cancer; Breast Neoplasms; Cancer of the Breast
• Interventions: Drug: docetaxel; Drug: gemcitabine; Drug: capecitabine

• Registration Number: NCT00191152
• Lead Sponsor: Eli Lilly and Company

Brief Summary

This is a phase III randomized study between the docetaxel/gemcitabine and docetaxel/ capecitabine doublets, with crossover to the alternate agent. The experimental arm will receive gemcitabine 1000 mg/m2 intravenous (IV) over 30 minutes days 1 and 8 and docetaxel 75 mg/m2 IV day 1 over 1 hour repeated every three weeks. The comparator arm will receive docetaxel 75 mgm/m2 IV day 1 over 1 hour and oral capecitabine 1000 mg/m2 twice daily, days 1 through 14 repeated every three weeks. Patients who progress on the experimental arm, will be treated with capecitabine as dosed on the comparator arm. Patients who progress on the comparator arm will be treated with gemcitabine as dosed on the experimental arm.

Detailed Description

Not available

Study Timeline

• Study Start: 2002-02
• Study First Submitted: 2005-09-12
• Study First Submitted QC: 2005-09-12
• Study First Posted: 2005-09-19
• Primary Completion: 2008-11
• Study Completion: 2008-11
• Results First Submitted: 2009-11-04
• Results First Submitted QC: 2009-11-04
• Status Verified: 2009-12
• Results First Posted: 2009-12-08
• Last Update Submitted: 2009-12-21
• Last Update Posted: 2009-12-24

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 475

Inclusion Criteria

• Histologic or cytologic confirmation of breast cancer with locally advanced and/or metastatic disease
• Patients may have received prior neo-adjuvant or adjuvant taxane regimen as long as it has been greater than or equal to 6 months since completion of the regimen
• Patients may have had 0-1, but no more than one prior course of chemotherapy for metastatic disease
• Patients must have either measurable or non-measurable (evaluable) disease
• Prior radiation therapy allowed of less than 25% of the bone marrow

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Exclusion Criteria

• Second primary malignancy (except in situ carcinoma of the cervix or adequately treated nonmelanomatous carcinoma of the skin or other malignancy treated at least 5 years previously with no evidence of recurrence)
• Parenchymal or leptomeningeal brain metastases
• Peripheral neuropathy greater than or equal to grade 2
• Prior treatment with gemcitabine and capecitabine will not be allowed. Prior treatment with a taxane in the metastatic setting will not be allowed. Prior taxane therapy in the neo-adjuvant or adjuvant setting is allowed if completion of therapy greater than or equal to 6 months prior to enrollment.
• Active cardiac disease not controlled by therapy and/or myocardial infarction within the preceding 6 months.
• Concomitant Herceptin is not allowed

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Capecitabine + Docetaxel	docetaxel	-
Gemcitabine + Docetaxel	gemcitabine	-
Gemcitabine + Docetaxel	docetaxel	-
Capecitabine + Docetaxel	capecitabine	-

Primary Outcome Measures

Name	Time	Method
Time to Disease Progression (Initial Treatment)	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)	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.

Secondary Outcome Measures

Name	Time	Method
Time to Disease Progression (Crossover Treatment)	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)	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.
Progression-Free Survival (Initial Treatment)	Date of randomization until the date of first documented progression or date of death from any cause, whichever came first (up to 82 months)	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.
Progression-Free Survival (Crossover Treatment)	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)	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.
Duration of Response (Initial Treatment)	Date of response (CR or PR) until the first date of documented progression or death from any cause (up to 82 months)	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.
Duration of Response (Crossover Treatment)	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)	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.
Overall Survival	Date of randomization to date of death from any cause (up to 82 months)	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.
Best Overall Response (Initial Treatment)	Best response from start of treatment until disease progression/recurrence (up to 82 months)	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.
Best Overall Response (Crossover Treatment)	Best response from start of treatment until disease progression/recurrence (up to 82 months)	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.
Summary of Changes in Karnofsky Performance Status (KPS) by Treatment (Initial Treatment)	Baseline until crossover treatment began (up to 82 months)	KPS ranges from 0 to 100, subdivided into three categories: incapacitated (0-40), self-care (50-70), and normal activity (80-100).
Summary of Changes in Karnofsky Performance Status (KPS) by Treatment (Crossover Treatment)	First day of crossover treatment until end of crossover treatment at trial discontinuation (up to 82 moths)	KPS ranges from 0 to 100, subdivided into three categories: incapacitated (0-40), self-care (50-70), and normal activity (80-100).
Summary of Changes in Rotterdam Symptom Checklist (RSCL) by Treatment (Initial Treatment)	Baseline until crossover treatment began (up to 82 months)	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 \[low score represents better QOL\].
Summary of Changes in Rotterdam Symptom Checklist by Treatment (Crossover Treatment)	First day of crossover treatment until end of crossover treatment at trial discontinuation (up to 82 months)	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 \[low score represents better QOL\].

Trial Locations

Locations (4)

For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1877-285-4559, 1-317-615-4559) Mon-Fri from 9AM to 5PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.; 🇲🇽 Michoacan, Mexico

For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon-Fri from 9AM to 5PM Eastern Time (UTC/GMT-5 hours, EST), or speak with your personal physician.; 🇨🇳 Taipei, Taiwan

For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Monday-Friday from 9:00 AM to 5:00 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal ph; 🇨🇳 Tao-Yuan, Taiwan

For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon-Fri from 9AM to 5PM Eastern Time (UTC/GMT-5 hours, EST), or speak with your personal physician.c; 🇺🇸 Dunmore, Pennsylvania, United States