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

NCT00370552 | Completed Phase 2 Results

• 1 other identifier: CA163-115
• Study Type: interventional
• Target: 136
• Locations: 5 countries
• Sites: 25

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

Outcome Measures

Primary Outcomes (2)

• Percentage of Participants With Best Tumor Response of Partial Response (PR) or Complete Response (CR) While On-study

  CR=Disappearance of all clinical and radiologic evidence of target lesions; PR=At least 30% reduction in the sum of the longest diameter of all target lesions.

  Baseline visit and then every 8 weeks to 12 months, then every 3 months until disease progression

• Number of Participants With Best Response As Assessed With Response Evaluation Criteria in Solid Tumors (RECIST)

  Best tumor response was assessed with RECIST. Complete response (CR)=Disappearance of all evidence of target lesions; Partial response (PR)=At least 30% reduction from baseline in the sum of the longest diameter (LD) of all target lesions; Progressive disease (PD)=At least a 20% increase from baseline in the sum of LD of target lesions or the appearance of 1 or more new lesions; Stable disease (SD)=Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. A response was confirmed if noted on 2 examinations at least 4 weeks apart.

  Baseline visit and then every 8 weeks to 12 months, then every 3 months until disease progression

Secondary Outcomes (9)

• Percentage of Participants With Progression-free Survival at Week 24

  Date of randomization to Week 24

• Median Progression-free Survival (PFS)

  Date of randomization to date of progression, death, or last tumor assessment (maximum participant PFS of 29 months)

• Median Time to Response

  Date of first PR or CR assessment to date of progression, death, or last tumor assessment (maximum participant time to response of 67 weeks)

• Median Duration of Response

  Date of first PR or CR assessment to date of progression, death, or last tumor assessment (maximum participant duration of response of 25 weeks)

• Percentage of Participants Surviving at 1 Year

  Date first participant enrolled to 1 year

Study Arms (3)

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

EXPERIMENTAL

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

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

EXPERIMENTAL

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

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

ACTIVE COMPARATOR

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

Interventions

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

Also known as: IXEMPRA, BMS-247550

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

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

Also known as: IXEMPRA, BMS-247550

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

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

Also known as: TAXOL, BMS-181339

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

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• R-Pharm: lead

Study Sites (25)

East Valley Hematology And Oncology Medical Group

Burbank, California, 91505, United States

Location

Wilshire Oncology Medical Group, Inc.

La Verne, California, 91750, United States

Location

Ucsf-Comprehensive Cancer Center

San Francisco, California, 94115, United States

Location

University Of Iowa Hospitals And Clinics

Iowa City, Iowa, 52242, United States

Location

Ellis Fischel Cancer Center

Columbia, Missouri, 65203, United States

Location

Weill Medical College Of Cornell University

New York, New York, 10021, United States

Location

Local Institution

Besançon, 25030, France

Location

Local Institution

Clermont-Ferrand, 63000, France

Location

Local Institution

Marseille, 13273, France

Location

Local Institution

Paris, 75475, France

Location

Local Institution

Saint-Herblain, 44805, France

Location

Local Institution

Strasbourg, 67085, France

Location

Local Institution

Tours, 37044, France

Location

Local Institution

Cuneo, 12100, Italy

Location

Local Institution

Meldola Fc, 47014, Italy

Location

Local Institution

Milan, 20132, Italy

Location

Local Institution

Modena, 41100, Italy

Location

Local Institution

Napoli, 80131, Italy

Location

Local Institution

Roma, 00161, Italy

Location

Local Institution

Jaén, 23007, Spain

Location

Local Institution

L'Hospitalet de Llobregat, 08907, Spain

Location

Local Institution

Chelmsford, Essex, CM1 7ET, United Kingdom

Location

Local Institution

Manchester, Greater Manchester, M20 4BX, United Kingdom

Location

Local Institution

Merseyside, Merseyside, CH63 4JY, United Kingdom

Location

Local Institution

Nottingham, Nottinghamshire, NG5 1PB, United Kingdom

Location

Related Links

• Investigator Inquiry form

MeSH Terms

Conditions

Breast Neoplasms

Interventions

ixabepilone; Bevacizumab; Paclitaxel; BMS 181339

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Results Point of Contact

• Title: BMS Study Director
• Organization: Bristol-Myers Squibb

Clinical.Trials@bms.com

Study Officials

• Bristol-Myers Squibb

  Bristol-Myers Squibb

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 30, 2006
• First Posted: August 31, 2006
• Study Start: March 1, 2007
• Primary Completion: November 1, 2009
• Study Completion: November 1, 2009
• Last Updated: March 10, 2016
• Results First Posted: April 14, 2011

Record last verified: 2016-02

Locations

US (6); FR (7); ES (2); GB (4); IT (6)