A Phase I Study of Ixabepilone in Combination With Capecitabine in Japanese Patients With Metastatic Breast Cancer

Study Overview
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Brief Summary
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The purpose of this study is to determine the dose-limiting toxicity (DLT), maximum tolerated dose (MTD) and recommended Phase II dose of ixabepilone in combination with capecitabine in Japanese participants with metastatic breast cancer.

Official Title
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A Phase I Study of Ixabepilone in Combination With Capecitabine in Japanese Patients With Metastatic Breast Cancer Previously Treated With an Anthracycline and a Taxane

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: Ixabepilone
* Drug: Capecitabine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Women ≥ 20 years Histologically or cytologically confirmed diagnosis of adenocarcinoma originating in the breast Exclusion Criteria: Number of prior chemotherapy lines of treatment in the metastatic setting ≥3

Ages Eligible for Study
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Minimum Age: 20 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: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ixabepilone + Capecitabine<br> | Drug: Ixabepilone<br>* Ixabepilone: Intravenous (IV) Solution, IV, 32(40)mg/m^2, once every 3 weeks, up to 6 cycles<br>* Other names: BMS-247550;Drug: Capecitabine<br>* Capecitabine: Tablets, Oral, 1650(2000)mg/m^2, twice daily for 2 weeks, one week off, up to 6 cycles<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Participants Experiencing Dose Limiting Toxicity (DLT) | DLT was defined as any ixabepilone and/or capecitabine related events requiring study discontinuation during the first two treatment cycles. | From initiation of drug through last day of Cycle 2 (Day 42) | 
| Participants Achieving the Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D) | The MTD was defined as the highest dose evaluated for which less than 1/3 of the participants experienced DLT during the first two treatment cycles. If toxicities (e.g. hand-foot syndrome, existing peripheral neuropathy, etc.) occurred or became more severe in later cycles, the recommended Phase II dose was to be determined after due consideration of their severity. | At the end of Cycle 2 (Day 42) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse Events (AEs) and Serious Adverse Events (SAEs) | AE = any new untoward medical occurrence/worsening of a pre-existing medical condition which does not necessarily have a causal relationship with this treatment. SAE = any untoward medical occurrence that at any dose: results in death, is life-threatening, requires inpatient hospitalization or causes prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, results in development of drug dependency or drug abuse, is an important medical event. Treatment-related=Possible, Probable, or Certain relationship to drug | Baseline to Day 42, continuously | 
| Participant Tumor Response at Study Endpoint | Tumor response was assessed using the Response Evaluation Criteria in Solid Tumors (RECIST) in which complete response (CR) = disappearance of all target lesions; partial response (PR) = 30% decrease in the sum of the longest diameter of target lesions; progressive disease (PD) = 20% increase in the sum of the longest diameter of target lesions; and stable disease (SD) = small changes that do not meet above criteria. | At baseline and after every 42 days (every 2 21-day cycles) after baseline | 
| Mean Ixabepilone Maximum Plasma Concentration (Cmax) in One Dosing Interval | Cmax = maximum observed plasma concentration of ixabepilone as determined from participant serum samples in one dosing interval. | During Cycle 1 at specified timepoints (Day 1 to Day 8). | 
| Mean Ixabepilone Area Under the Concentration Curve (AUC INF) in One Dosing Interval | AUC = the average area under the concentration curve (AUC [INF]) of ixabepilone as determined from participant serum samples in one dosing interval over 24 hours. | During Cycle 1 at specified timepoints (Day 1 to Day 8). | 
| Mean Ixabepilone Terminal Elimination Half Life (T 1/2) in One Dosing Interval | T 1/2 = terminal elimination half life as determined from participant serum samples in one dosing interval. | During Cycle 1 at specified timepoints (Day 1 to Day 8). | 
| Mean Ixabepilone Volume of Distribution at Steady State (Vss) in One Dosing Interval | Vss = volume of distribution at steady state determined from participant serum samples from one dosing interval. | During Cycle 1 at specified timepoints (Day 1 to Day 8). | 
| Mean Ixabepilone Total Body Clearance (CLT) in One Dosing Interval | CLT = total body clearance as determined from participant serum samples in one dosing interval. | During Cycle 1 at specified timepoints (Day 1 to Day 8). |