Novel Epothilone 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 is better than capecitabine alone in shrinking or slowing the growth of the cancer in women with metastatic breast cancer who are resistant to taxane and received anthracycline chemotherapy. The safety of this treatment will also be studied.

Official Title
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A Phase III Trial of Novel Epothilone BMS-247550 Plus Capecitabine Versus Capecitabine Alone in Patients With Advanced Breast Cancer Previously Treated With or Resistant to an Anthracycline and Who Are Taxane Resistant

Conditions
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Breast Cancer, Metastases

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 either 2 or 3 prior chemotherapy regimens including adjuvant or neoadjuvant therapy. Prior treatment must have included both an anthracycline (i.e., doxorubicin or epirubicin) and a taxane (i.e., paclitaxel or docetaxel). Patients must have received a minimum cumulative dose of anthracycline or must be resistant to an anthracycline. Patients must be resistant to taxane therapy. Patients may not have any history of brain and/or leptomeningeal metastases. Patients may not have CTC Grade 2 or greater neuropathy (motor or sensory). Patients may have not have had prior treatment with an epothilone 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 - Intravenous Solution, IV 40mg/m², Day 1 every 21 days, Until progression/unacceptable toxicity Capecitabine (Active Comparator) - Tablet, Oral, 2000 mg/m², Bid Days 1-14 every 21 days, Until progression/unacceptable toxicity<br>* Other names: Epothilone;|
| Active Comparator: B<br> | Drug: Capecitabine<br>* Tablet, Oral, 2500 mg/m², Bid Days 1-14 every 21 days, Until progression/unacceptable toxicity<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free Survival (PFS) Per Independent Radiology Review Committee (IRRC) | PFS defined as the time in months from randomization to date of progression. Patients who died without a reported prior progression were considered to have progressed on date of death; those who didn't progress or die were censored on date of last tumor assessment. Median PFS time with 95% CI estimated using the Kaplan Meier product limit method. | based on assessments every 6 weeks while on treatment until documented disease progression/unacceptable toxicity | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Response Rate (ORR) Per IRRC | Participants with best response of Complete or Partial according to Response Evaluation Criteria in Solid Tumors (RECIST) a 4-item scale wherein complete response=disappearance of all target lesions and partial response=30% decrease in the sum of the longest diameter of target lesions | based on assessments every 6 weeks while on treatment until documented disease progression/unacceptable toxicity | 
| Duration of Response Per IRRC | Computed for all patients with a best response of Partial or Complete per RECIST (a 4-item scale as described in previous outcome measure), calculated from the time when these criteria were first met until the first date of documented progression or death. | based on assessments every 6 weeks while on treatment until documented disease progression/unacceptable toxicity | 
| Time to Response Per IRRC | Time to response was summarized using descriptive statistics and was defined as the time from first dose of study treatment until measurement criteria were first met for Partial Response or Complete Response. | based on assessments every 6 weeks while on treatment until documented disease progression/unacceptable toxicity | 
| Overall Survival (OS) | OS was defined as the time from randomization to death. Participants who did not die at the time of the analysis were censored at the latest follow-up date. Median OS with 95% CI was estimated using the Kaplan Meier product limit method. | from date of randomization until death | 
| 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. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Metastatic Breast Cancer