Epothilone (Ixabepilone) Plus Capecitabine Versus Capecitabine Alone in Patients With Advanced Breast Cancer

Study Overview
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Brief Summary
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The purpose of this clinical research study is to learn if BMS-247550 added to the approved therapy of capecitabine (Xeloda) provides measurable clinical benefits over capecitabine alone in women with metastatic breast cancer. Patients should have previously received an anthracycline and a taxane. The safety of this treatment will also be studied.

Official Title
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A Phase III Study of Novel Epothilone (Ixabepilone) Plus Capecitabine Versus Capecitabine Alone in Patients With Advanced Breast Cancer Previously Treated With an Anthracycline and a Taxane

Conditions
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Cancer, Breast Cancer

Intervention / Treatment
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* Drug: Ixabepilone + Capecitabine
* Drug: Capecitabine


Participation Criteria
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Eligibility Criteria
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Patients must have received prior treatment which included both an anthracycline (i.e., doxorubicin or epirubicin) and a taxane (i.e., paclitaxel or docetaxel). Patients must have received no more than two prior chemotherapy regimens. Patients who have not received treatment for metastatic disease must have relapsed within one year. Patients may not have any history of brain and/or leptomeningeal metastases. Patients may not have Grade 2 or worse neuropathy at the time of study entry. Patients may not have had prior treatment with any epothilones and/or capecitabine (i.e. Xeloda)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A<br> | Drug: Ixabepilone + Capecitabine<br>* Ixabepilone lypholized powder/Diluent for solution for injection/Tablets, IV/Oral, 40 mg/m2 + Capecitabine 2000 mg/m2, Ixabepilone on Day 1 and Capecitabine twice daily Days 1-14 of 21 day cycle<br>* Other names: Epothilone;|
| Active Comparator: B<br> | Drug: Capecitabine<br>* Tablet, Oral, 2500 mg/m2, Capecitabine twice daily Days 1-14 of 21 day cycle<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival (OS) | Overall survival was defined as the time in months from randomization until the date of death. For those patients who had not died, survival duration was censored at the last date the patient was known to be alive. Median OS with 95% CI estimated using the Kaplan-Meier Product Limit Method. | from date of randomization until death | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-Free Survival (PFS) | PFS was defined for each patient as the time in months from randomization to the date of progression. Patients who died without a reported prior progression were considered to have progressed on their date of death. Patients who did not progress or die were censored on the date of their last tumor assessment. | every 6 weeks (± 3 days) from randomization while on treatment until documented progression | 
| Response Rate (RR) | RR=number of patients in that group whose best response is partial(30% decrease in the sum of the longest diameter of target lesions) or complete (disappearance of all target lesions), according to the 4-item Response Evaluation Criteria in Solid Tumors (RECIST), divided by the total number of response-evaluable participants | every 6 weeks (± 3 days) from randomization while on treatment until documented progression | 
| Duration of Response | Measured from the time RECIST criteria (described in previous outcome measure) were first met for complete or partial response until first date of documented disease progression or death. Patients who neither relapsed nor died were censored on the date of last tumor assessment. Median w/ 95% CI estimated using Kaplan Meier Product Limit Method. | every 6 weeks (± 3 days) from randomization while on treatment until documented progression | 
| Time to Response | Time to response was defined as the time from the first dose of study therapy until measurement criteria were first met for partial or complete (whichever status was recorded first) per RECIST criteria (a 4-item scale described in the previous outcome measure). | every 6 weeks (± 3 days) from randomization while on treatment until documented progression | 
| Treatment-Related Safety Summary | Laboratory values, adverse events, and other symptoms were graded using the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTC) Version 3.0 | safety was assessed on a continual basis every cycle while on-treatment and every 4 weeks post treatment until toxicities resolved or were deemed irreversible. | 
| Symptom Assessment Score Changes From Baseline for Functional Assessment of Cancer Therapy-Breast Symptom Index (FBSI) | Quality of life, as measured by the FBSI, an 8-item, participant-reported instrument to measure symptoms. Each item has 5 possible responses ranging from 0 (not at all) to 4 (very much). The scoring was conducted according to the Functional Assessment of Chronic Illness Therapy manual, Version 4; higher scores reflect fewer symptoms. | Baseline and prior to each 21-day cycle of treatment, and at first posttreatment follow-up assessment |