Randomized Study Evaluating Ixabepilone Plus Capecitabine or Docetaxel Plus Capecitabine in Metastatic Breast Cancer

Study Overview
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Brief Summary
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The purpose of this study is to assess the effect of ixabepilone plus capecitabine or docetaxel plus capecitabine on shrinking or slowing the growth of metastatic breast cancer in women. The safety of this combination therapy will also be evaluated.

Official Title
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IXTEND: A Randomized Phase 2 Study to Evaluate the Combination of Ixabepilone Plus Capecitabine or Capecitabine Plus Docetaxel in the Treatment of Metastatic Breast Cancer

Conditions
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Breast Neoplasms

Intervention / Treatment
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* Drug: Ixabepilone, 40 mg/m^2 + Capecitabine, 1000 mg/m^2
* Drug: Ixabepilone, 32 mg/m^2 + Capecitabine, 1000 mg/m^2
* Drug: Docetaxel, 75 mg/m^2 + Capecitabine, 1000 mg/m^2


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants with metastatic breast cancer Measurable disease Up to 1 chemotherapy regimen is acceptable. Participants who have received paclitaxel in the neoadjuvant or adjuvant setting acceptable, only if the last dose of paclitaxel was received 12 months or less before the treatment. There is no timeframe for prior paclitaxel in the metastatic setting. Human epidermal growth factor receptor 2-positive participants allowed if they have progressed after receiving treatment with trastuzumab or lapatinib Eastern Cooperative Oncology Group Performance status of 0-1 Age younger than 18 years Women of childbearing potential must be using an adequate method of contraception to avoid pregnancy throughout the study and for at least 4 weeks after the last dose of investigational products Exclusion Criteria: More than 1 chemotherapy regimen for the treatment of metastatic breast cancer Prior treatment with any epothilone, capecitabine, or docetaxel Prior radiation must not have included 30% or more of major bone marrow-containing areas (pelvis, lumbar spine). If prior radiation was less than 30%, a minimum interval of 2 weeks must be allowed between the last radiation treatment and administration of study medication. There must be at least 1 week between focal/palliative radiation and administration of study medication. Any current or previous history of brain and/or leptomeningeal metastases Neuropathy greater than Grade 2 Any concurrent malignancy other than nonmelanoma skin cancer or carcinoma in situ of the cervix Uncontrolled diabetes mellitus Chronic hepatitis HIV-positive status Administration of trastuzumab, lapatinib, bevacizumab, or other systemic treatment for cancer must be discontinued 28 days prior to study medication. Hormonal anticancer agents must be discontinued at least 14 days prior to study medication. Hormonal replacement therapy is acceptable Biphosphonates for palliation of bone metastases allowed if initiated at least 7 days before study entry

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

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: Ixabepilone, 40 mg/m^2 + Capecitabine, 1000 mg/m^2<br> | Drug: Ixabepilone, 40 mg/m^2 + Capecitabine, 1000 mg/m^2<br>* Ixabepilone, 40 mg/m^2, administered as a 3-hour intravenous (IV) infusion on Day 1 of a 21-day cycle plus capecitabine, 1000 mg/m^2, self-administered on an outpatient basis twice daily by mouth on Days 1 through 14 (±2 days) of each 21-day cycle.<br>* Other names: BMS-247550;|
| Experimental: Ixabepilone, 32 mg/m^2 + Capecitabine, 1000 mg/m^2<br> | Drug: Ixabepilone, 32 mg/m^2 + Capecitabine, 1000 mg/m^2<br>* Ixabepilone, 32 mg/m^2, administered as a 3-hour IV infusion on Day 1 of a 21-day cycle plus capecitabine, 1000 mg/m^2, self-administered on an outpatient basis twice daily by mouth on Days 1 through 14 (±2 days) of each 21-day cycle.<br>|
| Active Comparator: Docetaxel, 75 mg/m^2 + Capecitabine, 1000 mg/m^2<br> | Drug: Docetaxel, 75 mg/m^2 + Capecitabine, 1000 mg/m^2<br>* Docetaxel 75 mg/m^2 administered as a 1-hour IV infusion on Day 1 of a 21-day cycle plus capecitabine, 1000 mg/m^2, self-administered on an outpatient basis twice daily by mouth on Days 1 through 14 (±2 days) of each 21-day cycle.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Best Tumor Response as Assessed With Response Evaluation Criteria in Solid Tumors (RECIST) | RECIST definitions: Complete reponse (CR)=disappearance of all nontarget lesions; partial response (PR)=at least 30% reduction in the sum of the longest diameter (LD) of all target lesions in reference to the baseline sum LD; stable disease (SD)=neither PR nor progressive disease (PD) criteria were met; PD=at least 20% increase in the sum of the LD of all target lesions, taking as reference the smallest sum LD recorded at or following baseline. Tumor status assessed by investigator. | Baseline to 6 weeks (end of Cycle 2) | 
| Percentage of Participants With Best Response to Treatment of Complete or Partial | The tumor response rate is defined as the number of participants with a best tumor response of CR or PR (as assessed by the investigator according to RECIST criteria), divided by the number of participants randomized in that arm. | Baseline to 6 weeks (end of Cycle 2) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Triple-negative (TN) Participants With Best Response to Treatment of Complete or Partial | The tumor response rate is defined as the total number of participants whose best response is CR or PR, divided by the number of randomized participants. Participants not evaluable for response are considered to be nonresponders. TN participants are those with tumors that do not express estrogen or progesterone receptors and that do not over express human epidermal growth factor receptor 2 (HER2). | Baseline to 6 weeks (end of Cycle 2) | 
| Percentage of Nontriple-negative (NTN) Participants With Best Response to Treatment of Complete or Partial Per Cohort | The tumor response rate is defined as the total number of participants whose best response is CR or PR, divided by the number of randomized participants. Participants not evaluable for response are considered to be nonresponders. NTN participants are who are not TN participants (TN participants are those with tumors that do not express estrogen or progesterone receptors and that do not overexpress HER2) and who received ixabepilone plus capecitabine or docetaxel plus capecitabine. | Baseline to 6 weeks (end of Cycle 2) | 
| Number of Participants With Death, Adverse Events (AEs), Drug-related AEs, Serious AEs (SAEs), Drug-related SAEs, AEs Leading to Discontinuation (AEDs), Drug-related AEDs, and Drug-related Peripheral Neuropathy | An AE is any new untoward medical occurrence or worsening of a preexisting medical condition that does not necessarily have a causal relationship with this treatment. An SAE is any untoward medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency or abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. Drug-related=possibly, probably, or certainly related or of unknown relationship to study treatment. Grade 3=Severe, Grade 4=Life-threatening. | Baseline to end of Cycle 1 (21 days), continuously | 
| Number of Participants With Abnormalities in Hematology Laboratory Results by Worst Common Terminology Criteria (CTC) Grade | CTC Grade 1=Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2=Moderate; minimal, local or noninvasive intervention indicated. Grade 3=Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling. Grade 4=Life-threatening consequences; urgent intervention indicated. | Baseline in Cycle 1 (21 days) and then prior to start of each 21-day cycle | 
| Number of Participants With Abnormalities in Serum Chemistry Laboratory Results | ULN=Upper limit of normal among all laboratory ranges. Alanine aminotransferase (ALT) Grade 1:>ULN to 2.5*ULN; Grade 2: >2.5 to 5.0*ULN; Grade 3: >5.0 to 20.0*ULN; Grade 4: >20.0*ULN. Aspartate aminotransferase (AST) Grade 1: >ULN to 2.5*ULN; Grade 2: >2.5 to 5.0*ULN; Grade 3: >5.0 to 20.0*ULN; Grade 4: >20.0*ULN. Total bilirubin Grade 1: >ULN to 1.5*ULN; Grade 2: >1.5 to 3.0*ULN; Grade 3: >3.0 to 10.0*ULN; Grade 4: >10.0*ULN. Creatine Grade 1: >ULN to 1.5*ULN; Grade 2: 1.5 to 3.0*ULN; Grade 3: >3.0 to 6.0*ULN; Grade 4: >6.0*ULN. | Baseline in Cycle 1 (21 days) and then prior to start of each 21-day cycle | 
| Time to Progression | Time to progression is defined as the time from date of randomization until the date that PD is first reported. Participants who die without a reported prior progression are considered to have progressed on the day of their death. Those who did not progress or die are censored at the day of their last tumor assessment. | Baseline to date progressive disease reported | 
| Duration of Response | Duration of overall response is computed for participants whose best response is either PR or CR and is measured from the time measurement criteria are first met for CR or PR (whichever status is recorded first) until the first date of documented PD or death. Participants who did not relapse or die are censored on the date of their last tumor assessment. | Baseline (date of randomization) to date CR or PR criteria first met | 
| Median Number of Treatment Cycles | The first dosing date is defined as the date of the first dose of chemotherapy or capecitabine, whichever was administered first. Cycles are defined as the time from Day 1 of the cycle until the day before the next cycle. The last cycle per participant is the 21-day period following Day 1 of that cycle. | Day 1 to end of Cycle 18, maximum (54 weeks) |