Novel Epothilone Plus Capecitabine Versus Capecitabine Alone in Patients With Advanced Breast Cancer

• ClinicalTrials.gov Identifier: NCT00080301
• Recruitment Status: Completed
• First Posted: March 30, 2004
• Results First Posted: August 17, 2009
• Last Update Posted: November 2, 2020
• Sponsor: R-Pharm
• Information provided by: R-Pharm

Tracking Information

• First Submitted Date: March 26, 2004
• First Posted Date: March 30, 2004
• Results First Submitted Date: May 1, 2009
• Results First Posted Date: August 17, 2009
• Last Update Posted Date: November 2, 2020
• Study Start Date: September 2003
• Actual Primary Completion Date: November 2006 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: July 2, 2009)

Progression-free Survival (PFS) Per Independent Radiology Review Committee (IRRC) [ Time Frame: based on assessments every 6 weeks while on treatment until documented disease progression/unacceptable toxicity ]

PFS defined as the time in months from randomization to date of progression. Patients who died without a reported prior progression were considered to have progressed on date of death; those who didn't progress or die were censored on date of last tumor assessment. Median PFS time with 95% CI estimated using the Kaplan Meier product limit method.

• Original Primary Outcome Measures: Not Provided

Current Secondary Outcome Measures (submitted: July 2, 2009)

• Overall Response Rate (ORR) Per IRRC [ Time Frame: based on assessments every 6 weeks while on treatment until documented disease progression/unacceptable toxicity ]
  Participants with best response of "Complete" or "Partial" according to Response Evaluation Criteria in Solid Tumors (RECIST) a 4-item scale wherein complete response=disappearance of all target lesions and partial response=30% decrease in the sum of the longest diameter of target lesions
• Duration of Response Per IRRC [ Time Frame: based on assessments every 6 weeks while on treatment until documented disease progression/unacceptable toxicity ]
  Computed for all patients with a best response of "Partial" or "Complete" per RECIST (a 4-item scale as described in previous outcome measure), calculated from the time when these criteria were first met until the first date of documented progression or death.
• Time to Response Per IRRC [ Time Frame: based on assessments every 6 weeks while on treatment until documented disease progression/unacceptable toxicity ]
  Time to response was summarized using descriptive statistics and was defined as the time from first dose of study treatment until measurement criteria were first met for Partial Response or Complete Response.
• Overall Survival (OS) [ Time Frame: from date of randomization until death ]
  OS was defined as the time from randomization to death. Participants who did not die at the time of the analysis were censored at the latest follow-up date. Median OS with 95% CI was estimated using the Kaplan Meier product limit method.
• Treatment-related Safety Summary [ Time Frame: safety was assessed on a continual basis every cycle while on-treatment and every 4 weeks post treatment until toxicities resolved or were deemed irreversible. ]
  Laboratory values, adverse events, and other symptoms were graded using the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTC) Version 3.0
• Symptom Assessment Score Changes From Baseline for Functional Assessment of Cancer Therapy-Breast Symptom Index (FBSI) [ Time Frame: Baseline and prior to each 21-day cycle of treatment, and at first posttreatment follow-up assessment. ]
  Quality of life, as measured by the FBSI, an 8-item, participant-reported instrument to measure symptoms. Each item has 5 possible responses ranging from 0 (not at all) to 4 (very much). The scoring was conducted according to the Functional Assessment of Chronic Illness Therapy manual, Version 4; higher scores reflect fewer symptoms.

• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Novel Epothilone Plus Capecitabine Versus Capecitabine Alone in Patients With Advanced Breast Cancer
• Official Title: A Phase III Trial of Novel Epothilone BMS-247550 Plus Capecitabine Versus Capecitabine Alone in Patients With Advanced Breast Cancer Previously Treated With or Resistant to an Anthracycline and Who Are Taxane Resistant
• Brief Summary: The purpose of this clinical research study is to learn if BMS-247550 added to the approved therapy of capecitabine is better than capecitabine alone in shrinking or slowing the growth of the cancer in women with metastatic breast cancer who are resistant to taxane and received anthracycline chemotherapy. The safety of this treatment will also be studied.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Breast Cancer
• Metastases

Intervention

• Drug: Ixabepilone + Capecitabine

  Ixabepilone - Intravenous Solution, IV 40mg/m², Day 1 every 21 days, Until progression/unacceptable toxicity

  Capecitabine (Active Comparator) - Tablet, Oral, 2000 mg/m², Bid Days 1-14 every 21 days, Until progression/unacceptable toxicity

  Other Names:

  • BMS-247550
  • IXEMPRA
  • Epothilone
• Drug: Capecitabine
  Tablet, Oral, 2500 mg/m², Bid Days 1-14 every 21 days, Until progression/unacceptable toxicity

Study Arms

• Experimental: A
  Intervention: Drug: Ixabepilone + Capecitabine
• Active Comparator: B
  Intervention: Drug: Capecitabine

Publications *

• Thomas ES, Gomez HL, Li RK, Chung HC, Fein LE, Chan VF, Jassem J, Pivot XB, Klimovsky JV, de Mendoza FH, Xu B, Campone M, Lerzo GL, Peck RA, Mukhopadhyay P, Vahdat LT, Roche HH. Ixabepilone plus capecitabine for metastatic breast cancer progressing after anthracycline and taxane treatment. J Clin Oncol. 2007 Nov 20;25(33):5210-7. doi: 10.1200/JCO.2007.12.6557. Epub 2007 Oct 29.
• Vahdat LT, Vrdoljak E, Gomez H, Li RK, Bosserman L, Sparano JA, Baselga J, Mukhopadhyay P, Valero V. Efficacy and safety of ixabepilone plus capecitabine in elderly patients with anthracycline- and taxane-pretreated metastatic breast cancer. J Geriatr Oncol. 2013 Oct;4(4):346-52. doi: 10.1016/j.jgo.2013.07.006. Epub 2013 Aug 23.
• Jassem J, Fein L, Karwal M, Campone M, Peck R, Poulart V, Vahdat L. Ixabepilone plus capecitabine in advanced breast cancer patients with early relapse after adjuvant anthracyclines and taxanes: a pooled subset analysis of two phase III studies. Breast. 2012 Feb;21(1):89-94. doi: 10.1016/j.breast.2011.09.003. Epub 2011 Sep 21.
• Roche H, Conte P, Perez EA, Sparano JA, Xu B, Jassem J, Peck R, Kelleher T, Hortobagyi GN. Ixabepilone plus capecitabine in metastatic breast cancer patients with reduced performance status previously treated with anthracyclines and taxanes: a pooled analysis by performance status of efficacy and safety data from 2 phase III studies. Breast Cancer Res Treat. 2011 Feb;125(3):755-65. doi: 10.1007/s10549-010-1251-y. Epub 2010 Dec 3.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: October 9, 2008): 752
• Original Enrollment: Not Provided
• Actual Study Completion Date: March 2008
• Actual Primary Completion Date: November 2006 (Final data collection date for primary outcome measure)

Eligibility Criteria

• Patients must have received either 2 or 3 prior chemotherapy regimens including adjuvant or neoadjuvant therapy.
• Prior treatment must have included both an anthracycline (i.e., doxorubicin or epirubicin) and a taxane (i.e., paclitaxel or docetaxel).
• Patients must have received a minimum cumulative dose of anthracycline or must be resistant to an anthracycline.
• Patients must be resistant to taxane therapy.
• Patients may not have any history of brain and/or leptomeningeal metastases.
• Patients may not have CTC Grade 2 or greater neuropathy (motor or sensory).
• Patients may have not have had prior treatment with an epothilone and/or capecitabine (i.e., Xeloda)

Sex/Gender

• Sexes Eligible for Study: Female

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Argentina, Belgium, Brazil, Canada, China, France, Germany, Greece, Hungary, Italy, Korea, Republic of, Malaysia, Mexico, Peru, Philippines, Poland, Spain, Sweden, Taiwan, Thailand, United Kingdom, United States
• Removed Location Countries: Netherlands, Puerto Rico

Administrative Information

• NCT Number: NCT00080301
• Other Study ID Numbers: CA163-046
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Study Director, Bristol-Myers Squibb
• Original Responsible Party: Not Provided
• Current Study Sponsor: R-Pharm
• Original Study Sponsor: Bristol-Myers Squibb
• Collaborators: Not Provided

Investigators

• Study Director: Bristol-Myers Squibb; Bristol-Myers Squibb

• PRS Account: R-Pharm
• Verification Date: October 2020