Phase II Trial of Weekly or Every 3-week Ixabepilone for Patients With Metastatic Breast Cancer
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
|Official Title:||Phase II Randomized Trial of Weekly and Every 3-week Ixabepilone in Metastatic Breast Cancer (MBC) Patients|
- Progression-Free Survival (PFS) at 6 Months (6-month PFS Rate): Proportion of Participants Progression Free at 6 Months [ Time Frame: From the date of randomization to 6-months on study ]PFS at 6 months was defined as proportion of participants who neither progressed nor died before 6 months. Computed using Kaplan-Meier estimates.
- Median Progression Free Survival [ Time Frame: From the date of randomization to date of progression, death, or last tumor assessment (maximum participant PFS of 25.7 months) ]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.
- Overall Response Rate (ORR) Based on Response Criteria in Solid Tumors [RECIST] [ Time Frame: Assessed at 12-week intervals until disease progression (to a maximum follow-up for tumor response of 26.3 months) ]
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.
- Best Response as Assessed With RECIST [ Time Frame: Assessed at 12-week intervals until disease progression (to a maximum follow-up for tumor response of 26.3 months) ]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.
- Overall Survival (OS) [ Time Frame: From the date of randomization to date of death (maximum participant OS of 26.3 months) ]
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
- Time to Response [ Time Frame: From the date of first dose to date of first PR or CR assessment ( maximum participant time to response of 8.3 months) ]
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.
- Duration of Response [ Time Frame: 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) ]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.
- Incidence of All Grades of Peripheral Neuropathy [ Time Frame: 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). ]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.
- Number of Participants With Death as Outcome, Treatment-related (TR) Deaths, SAEs, TR SAEs, Adverse Events (AEs) Leading to Discontinuation, AEs, TR AEs, GR 3-4 AEs, TR GR 3-4 AEs, Drug-related (DR) Peripheral Neuropathy, Neutropenia, Alopecia [ Time Frame: Assessed from the date of first 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). ]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, drug dependency or abuse; is life-threatening, an important medical event, a congenital anomaly/birth defect; requires inpatient hospitalization; or prolongs existing hospitalization. Treatment related=possibly, probably, or certainly related to and of unknown relationship to study treatment. GR=Grade.
|Study Start Date:||May 2008|
|Study Completion Date:||August 2010|
|Primary Completion Date:||August 2010 (Final data collection date for primary outcome measure)|
Active Comparator: Arm 1
ixabepilone 16 mg/m^2 weekly for 3 weeks followed by 1 week rest
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.
Active Comparator: Arm 2
ixabepilone 40 mg/m^2 every 3 weeks
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00593827
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|Study Director:||Bristol-Myers Squibb||Bristol-Myers Squibb|