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

This study has been completed.
Sponsor:
Collaborator:
US Oncology Research
Information provided by (Responsible Party):
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT00593827
First received: January 4, 2008
Last updated: April 25, 2012
Last verified: April 2012
  Purpose

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.


Condition Intervention Phase
Metastatic Breast Cancer
Drug: Ixabepilone
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Randomized Trial of Weekly and Every 3-week Ixabepilone in Metastatic Breast Cancer (MBC) Patients

Resource links provided by NLM:


Further study details as provided by Bristol-Myers Squibb:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
    PFS at 6 months was defined as proportion of participants who neither progressed nor died before 6 months. Computed using Kaplan-Meier estimates.


Secondary Outcome Measures:
  • 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) ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: No ]

    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) ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: No ]

    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) ] [ Designated as safety issue: No ]

    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) ] [ Designated as safety issue: No ]
    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). ] [ Designated as safety issue: Yes ]
    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.


Enrollment: 176
Study Start Date: May 2008
Study Completion Date: August 2010
Primary Completion Date: August 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Arm 1
ixabepilone 16 mg/m^2 weekly for 3 weeks followed by 1 week rest
Drug: Ixabepilone
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.
Other Names:
  • IXEMPRA
  • BMS-247550
Active Comparator: Arm 2
ixabepilone 40 mg/m^2 every 3 weeks
Drug: Ixabepilone
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.
Other Names:
  • IXEMPRA
  • BMS-247550

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00593827

  Show 57 Study Locations
Sponsors and Collaborators
Bristol-Myers Squibb
US Oncology Research
Investigators
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
  More Information

Additional Information:
No publications provided

Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT00593827     History of Changes
Other Study ID Numbers: CA163-132, USOR 06-106
Study First Received: January 4, 2008
Results First Received: March 14, 2012
Last Updated: April 25, 2012
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Epothilones
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on July 29, 2014