A Trial of 2 Schedules of Ixabepilone Plus Bevacizumab and Paclitaxel Plus Bevacizumab for Breast Cancer

NCT ID: NCT00370552

Last Updated: 2016-03-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 136 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-03-31
• Study Completion Date: 2009-11-30

Brief Summary

The purpose of this clinical research study is to learn if ixabepilone plus bevacizumab is effective in shrinking or stopping the growth of cancer when given as first-line chemotherapy in participants with metastatic breast cancer. The study will also assess the safety of this combination treatment.

Conditions

Metastatic Breast Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Ixabepilone, 16 mg/m^2 + Bevacizumab, 10 mg/kg

Group Type: EXPERIMENTAL

Ixabepilone, 16 mg/m^2 + Bevacizumab, 10 mg/kg

Intervention Type: DRUG

Ixabepilone,16 mg/m\^2, administered as a 1-hour intravenous (IV) infusion on Days 1, 8, and 15 of a 28-day cycle until disease progression or unacceptable toxicity. Bevacizumab, 10 mg/kg, administered as IV infusion every 2 weeks. Bevacizumab to be infused over 90 minutes for the first dose, and if well tolerated for 60 minutes, for the second dose. Then if still tolerated, over 30 minutes for subsequent infusions. Bevacizumab was to be dosed until disease progression or unacceptable toxicity.

Ixabepilone, 40 mg/m^2 + Bevacizumab, 15 mg/kg

Group Type: EXPERIMENTAL

Ixabepilone, 40 mg/m^2 + Bevacizumab, 15 mg/kg

Intervention Type: DRUG

Ixabepilone, 40 mg/m\^2, administered as a 3-hour IV infusion on Day 1 of a 21-day cycle until disease progression or unacceptable toxicity (After Cycle 4, dose reduction to 32 mg/m\^2 was to be implemented for all subsequent cycles.) Bevacizumab, 15 mg/kg, administered as IV infusion every 3 weeks. Bevacizumab to be infused over 90 minutes for the first dose, and if well tolerated for 60 minutes, for the second dose. Then if still tolerated, over 30 minutes for subsequent infusions. Bevacizumab was to be dosed until disease progression or unacceptable toxicity.

Paclitaxel, 90 mg/m^2 + Bevacizumab, 10 mg/kg

Group Type: ACTIVE_COMPARATOR

Paclitaxel, 90 mg/m^2 + Bevacizumab, 10 mg/kg

Intervention Type: DRUG

Paclitaxel, 90 mg/m\^2, given as a 1-hour IV infusion on Days 1, 8, and 15 of a 28-day cycle until disease progression or unacceptable toxicity. Bevacizumab, 10 mg/kg, administered as IV infusion every 2 weeks. Bevacizumab infused over 90 minutes for the first dose, and if well tolerated, over 60 minutes for the second dose. If still tolerated, over 30 minutes for subsequent infusions. Bevacizumab was to be dosed until disease progression or unacceptable toxicity.

Interventions

Ixabepilone, 16 mg/m^2 + Bevacizumab, 10 mg/kg

Ixabepilone,16 mg/m\^2, administered as a 1-hour intravenous (IV) infusion on Days 1, 8, and 15 of a 28-day cycle until disease progression or unacceptable toxicity. Bevacizumab, 10 mg/kg, administered as IV infusion every 2 weeks. Bevacizumab to be infused over 90 minutes for the first dose, and if well tolerated for 60 minutes, for the second dose. Then if still tolerated, over 30 minutes for subsequent infusions. Bevacizumab was to be dosed until disease progression or unacceptable toxicity.

Intervention Type: DRUG

Ixabepilone, 40 mg/m^2 + Bevacizumab, 15 mg/kg

Ixabepilone, 40 mg/m\^2, administered as a 3-hour IV infusion on Day 1 of a 21-day cycle until disease progression or unacceptable toxicity (After Cycle 4, dose reduction to 32 mg/m\^2 was to be implemented for all subsequent cycles.) Bevacizumab, 15 mg/kg, administered as IV infusion every 3 weeks. Bevacizumab to be infused over 90 minutes for the first dose, and if well tolerated for 60 minutes, for the second dose. Then if still tolerated, over 30 minutes for subsequent infusions. Bevacizumab was to be dosed until disease progression or unacceptable toxicity.

Intervention Type: DRUG

Paclitaxel, 90 mg/m^2 + Bevacizumab, 10 mg/kg

Paclitaxel, 90 mg/m\^2, given as a 1-hour IV infusion on Days 1, 8, and 15 of a 28-day cycle until disease progression or unacceptable toxicity. Bevacizumab, 10 mg/kg, administered as IV infusion every 2 weeks. Bevacizumab infused over 90 minutes for the first dose, and if well tolerated, over 60 minutes for the second dose. If still tolerated, over 30 minutes for subsequent infusions. Bevacizumab was to be dosed until disease progression or unacceptable toxicity.

Intervention Type: DRUG

Other Intervention Names

IXEMPRA; BMS-247550; IXEMPRA; BMS-247550; TAXOL; BMS-181339

Eligibility Criteria

Inclusion Criteria

• Locally recurrent or metastatic breast cancer, previously untreated with chemotherapy for advanced disease.
• At least 1 target lesion per RECIST criteria. Locally recurrent disease must not be amenable to resection with curative intent.
• No previous cytotoxic chemotherapy for locally recurrent/metastatic disease.
• Relapse 12 months or more after completing prior adjuvant or neoadjuvant taxane therapy.
• No previous breast cancer known to overexpress or amplify the human epidermal growth factor receptor 2 gene.
• Prior hormonal therapy in adjuvant, recurrent, or metastatic setting allowed but must have been discontinued at least 2 weeks before randomization.
• Karnofsky performance status of 80 to 100 or Eastern Cooperative Oncology Group performance status of 0 to 1.
• Estimated life expectancy of at least 12 weeks.
• Recovery from recent therapy (except for alopecia), including chemotherapy, immunotherapy, biologic therapy, or investigational product. Any such therapy must have been completed at least 3 weeks before randomization and at least 6 weeks from use of nitrosourea, or mitomycin.
• Recovery from recent surgery and radiation therapy. At least 1 week since minor surgery and/or focal/palliative radiation therapy; at least 3 weeks from radiation; at least 4 weeks from major surgery; and at least 8 weeks from liver resection, thoracotomy, or neurosurgery.
• Absolute neutrophil count ≥1500/mm^3.
• Hemoglobin ≥9 g/dL.
• Platelets ≥100,000/mm^3.
• Total bilirubin ≤1.5 times the upper limit of normal (ULN).
• Aspartate aminotransferase or alanine aminotransferase ≤2.5*ULN.
• Normal partial thromboplastin time and either international normalized ratio or prothrombin time <1.5*ULN.
• Serum creatinine ≤1.5*ULN or 24-hour creatinine clearance >60 mL/min.
• Urine dipstick for proteinuria <2+ (negative, trace, or +1). Participants with ≥2+ proteinuria at baseline were to undergo 24-hour urine collection and demonstrate ≤1g of protein in 24 hours to be eligible.

Exclusion Criteria

• Women of child-bearing potential (WOCBP) unwilling or unable to use an acceptable method of birth control to avoid pregnancy for the entire study period and up to 6 months after treatment with bevacizumab.
• Women who were pregnant or breastfeeding.
• Women with a positive pregnancy test on enrollment or prior to study drug administration.
• Sexually active fertile men, whose partners were WOCBP, not using an adequate method of birth control.
• Evidence of baseline sensory or motor neuropathy.
• Serious infection or nonmalignant medical illnesses uncontrolled or the control of which could be jeopardized by this therapy.
• History of abdominal fistula, gastrointestinal perforation, intra-abdominal abscess, serious gastric ulcer, or bone fracture within 6 months of study entry.
• History of hypertensive crisis or hypertensive encephalopathy.
• Significant vascular disease.
• Clinically significant cardiovascular disease.
• Baseline left ventricular ejection fraction by multiple-gated acquisition scan or echocardiogram for subjects with prior exposure to anthracyclines not within institutional normal limits.
• Symptomatic peripheral vascular disease.
• History of high dose chemotherapy with bone marrow transplant or peripheral blood stem cell transplant within the previous 2 years.
• Evidence of bleeding diathesis or coagulopathy.
• Prior treatment with an epothilone or any antiangiogenic agent.
• Concurrent nonhealing wound, ulcer, or fracture.
• Any current or history of brain and/or leptomeningeal metastases. Psychiatric disorders or other conditions rendering the participant incapable of complying with the requirements of the protocol.
• Any concurrent active malignancy other than nonmelanoma skin cancer or carcinoma in situ of the cervix.
• Known allergy to any of the study drugs or their excipients.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

R-Pharm

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Bristol-Myers Squibb

Role: STUDY_DIRECTOR

Bristol-Myers Squibb

Locations

East Valley Hematology And Oncology Medical Group

Burbank, California, United States

Wilshire Oncology Medical Group, Inc.

La Verne, California, United States

Ucsf-Comprehensive Cancer Center

San Francisco, California, United States

University Of Iowa Hospitals And Clinics

Iowa City, Iowa, United States

Ellis Fischel Cancer Center

Columbia, Missouri, United States

Weill Medical College Of Cornell University

New York, New York, United States

Local Institution

Besançon, , France

Local Institution

Clermont-Ferrand, , France

Local Institution

Marseille, , France

Local Institution

Paris, , France

Local Institution

Saint-Herblain, , France

Local Institution

Strasbourg, , France

Local Institution

Tours, , France

Local Institution

Cuneo, , Italy

Local Institution

Meldola Fc, , Italy

Local Institution

Milan, , Italy

Local Institution

Modena, , Italy

Local Institution

Napoli, , Italy

Local Institution

Roma, , Italy

Local Institution

Jaén, , Spain

Local Institution

L'Hospitalet de Llobregat, , Spain

Local Institution

Chelmsford, Essex, United Kingdom

Local Institution

Manchester, Greater Manchester, United Kingdom

Local Institution

Merseyside, Merseyside, United Kingdom

Local Institution

Nottingham, Nottinghamshire, United Kingdom

Countries

United States; France; Italy; Spain; United Kingdom

Related Links

http://www.bms.com/clinical_trials/Pages/Investigator_Inquiry_form.aspx

Investigator Inquiry form

Other Identifiers

CA163-115

Identifier Type: -

Identifier Source: org_study_id