Phase II Trial of Weekly or Every 3-week Ixabepilone for Patients With Metastatic Breast Cancer

Study Overview
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Brief Summary
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The purpose of this study was to determine the effects of the weekly regimen of ixabepilone dosing compared to the once every 3 week dosing regimen in participants with metastatic breast cancer.

Official Title
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Phase II Randomized Trial of Weekly and Every 3-week Ixabepilone in Metastatic Breast Cancer (MBC) Patients

Conditions
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Metastatic Breast Cancer

Intervention / Treatment
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* Drug: Ixabepilone
* Drug: Ixabepilone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Has MBC that is measurable by RECIST or has nonmeasurable disease with serum CA27.29 (or CA15.3) ≥ 50 Has Human Epidermal Growth Factor Receptor 2 (HER2) negative breast cancer Prior chemotherapy is permitted with no limit on the number of prior regimens Two weeks or more have elapsed since last chemotherapy or radiation treatment Has an Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0-2 Is female, ≥ 18 yrs of age Protocol defined appropriate laboratory values Negative pregnancy test within 7 calendar days prior to registration Has signed a patient informed consent Exclusion Criteria: Had prior treatment with ixabepilone or other epothilones Has HER2+ disease Has a known, prior, severe (National Cancer Institute Common Terminology Criteria Adverse Events [NCI CTCAE] Grade 3-4) history of hypersensitivity reaction to a drug formulated in Cremophor ® EL (polyoxyethylated castor oil) Is receiving concurrent immunotherapy, hormonal therapy or radiation therapy Is receiving concurrent investigational therapy or has received such therapy within the past 30 days Has peripheral neuropathy > Grade 1 Has evidence of central nervous system (CNS) involvement requiring radiation or steroid treatment. Participants with stable brain metastases who are off steroids at least 2 weeks are eligible Is pregnant or breast feeding

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 |
| --- | --- |
| Active Comparator: Arm 1<br>ixabepilone 16 mg/m^2 weekly for 3 weeks followed by 1 week rest | Drug: Ixabepilone<br>* Injection, IV, Until progressive disease or intolerable toxicity Ixabepilone 16 mg/m^2 was administered as a 1-hour IV continuous infusion on Days 1, 8, and 15 in a 28-day cycle until progressive disease or intolerable toxicity.<br>* Other names: BMS-247550;|
| Active Comparator: Arm 2<br>ixabepilone 40 mg/m^2 every 3 weeks | Drug: Ixabepilone<br>* Injection, IV, Until progressive disease or intolerable toxicity Ixabepilone 40 mg/m^2 was administered as a 3-hour IV infusion on Day 1 of each 21-day cycle provided the subject met the retreatment criteria.<br>* Other names: BMS-247550;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-Free Survival (PFS) at 6 Months (6-month PFS Rate): Proportion of Participants Progression Free at 6 Months | PFS at 6 months was defined as proportion of participants who neither progressed nor died before 6 months. Computed using Kaplan-Meier estimates. | From the date of randomization to 6-months on study | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Median Progression Free Survival | PFS is defined as time interval from the date of randomization to the date of (first) progression or date of death. Participants who progressed or died were counted as events. Participants lost to follow-up were censored as of the last date of contact. Participants who started a new treatment before they progressed were censored as of the date of start of the new treatment. Participants who had not progressed or died were censored at the date of last follow-up. PFS (months) = (End date - date of randomization + 1)/30.4375. | From the date of randomization to date of progression, death, or last tumor assessment (maximum participant PFS of 25.7 months) | 
| Overall Response Rate (ORR) Based on Response Criteria in Solid Tumors [RECIST] | ORR is defined as the proportion of responders (complete response [CR] + partial response [PR] in participants with measurable disease) in that arm among all randomized participants. CR: Disappearance of all evidence of target lesions. PR: At least 30% reduction from baseline in the sum of the longest diameter (LD) of all target lesions. Measurable disease: Lesions that can be accurately measured in at least one dimension (LD to be recorded) as ≥20 mm with conventional techniques (computed tomography [CT], magnetic resonance imaging [MRI], X-ray) or as ≥10 mm with spiral CT scan. | Assessed at 12-week intervals until disease progression (to a maximum follow-up for tumor response of 26.3 months) | 
| Best Response as Assessed With RECIST | Determined based on the sequence of disease status with corresponding best response. PD=At least a 20% increase in the sum of LD of target lesions in reference to the smallest sum LD recorded or the appearance of 1 or more new lesions; SD=Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD in reference to the smallest sum LD. NE=Participants who discontinued treatment secondary to toxicity or died (either before completion of 1 treatment cycle). Please refer outcome measure 3 for explanation of CR and PR. CR+PR+SD=overall disease control. | Assessed at 12-week intervals until disease progression (to a maximum follow-up for tumor response of 26.3 months) | 
| Overall Survival (OS) | Survival was measured as the date of randomization to the date of death. Participants who were alive at the time of the database lock or lost to follow-up were censored at the last known alive date. The distribution of overall survival was analyzed via the Kaplan Meier method in each arm. Survival time (months) = (End date - date of randomization + 1)/30.4375 | From the date of randomization to date of death (maximum participant OS of 26.3 months) | 
| Time to Response | Time to response is defined as the time from the start of treatment until the first (confirmed) CR or PR was recorded. Time to response was computed only for participants whose best response was PR or CR. CR: Disappearance of all target lesions. PR: At least 30% reduction from baseline in the sum of the longest diameter (LD) of all target lesions with reference to the baseline sum LD. | From the date of first dose to date of first PR or CR assessment ( maximum participant time to response of 8.3 months) | 
| Duration of Response | Duration of overall response was defined as the period from the time first PR or CR was recorded until the first date of documented PD or death. Duration of response was computed for participants whose best response was either PR or CR. Participants who neither relapsed nor died were censored on the date of their last tumor assessment. Kaplan-Meier method was used to estimate the duration of response. Refer to outcome measures 3 and 4 for CR, PR, and PD. | From the date of first PR or CR assessment to date of progression, death, or last tumor assessment (maximum participant duration of response of 17.4 months) | 
| Incidence of All Grades of Peripheral Neuropathy | All events of peripheral neuropathy were assessed and graded per National Cancer Institute (NCI) Common Terminology Criteria Adverse Events (CTCAE)Version 3. CTC Grade (GR) 1=Mild; GR2=Moderate; GR3=Severe or medically significant, not immediately life-threatening; and GR4=Life-threatening. All treatment-related and not related Neuropathy and Peripheral Neuropathy were included; serious adverse events (SAEs) were not included. | Assessed from the date of first study dose until at least 30 days after the last dose of study drug. Median time on study therapy was 12 weeks (range: 4-60 weeks for 16 mg/m^2 arm; 3-87 weeks for 40 mg/m^2 arm). |