A Study to Evaluate the Safety and Efficacy of Bevacizumab in Combination With Chemotherapy in Previously Treated Metastatic Breast Cancer (RIBBON 2)

NCT00281697 | Completed Phase 3 Results

• 1 other identifier: AVF3693g
• Study Type: interventional
• Target: 684
• Locations: 0 countries
• Sites: N/A

Brief Summary

This phase III, multicenter, randomized, placebo-controlled, blinded trial is designed to evaluate the efficacy and safety of bevacizumab when combined with standard chemotherapy compared with chemotherapy alone in subjects with previously treated metastatic breast cancer.

Conditions

Metastatic Breast Cancer

Keywords

Ribbon 2; Avastin; MBC; Breast cancer

Outcome Measures

Primary Outcomes (1)

• Progression-free Survival

  PFS was defined as the time from randomization to first documented disease progression (PD) as determined by the investigator using Response Evaluation Criteria in Solid Tumors (RECIST) or death due to any cause, whichever occurred first. For target lesions, PD was defined as at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum of the longest diameter recorded since treatment started or the appearance of 1 or more new lesions. For non-target lesions, PD was defined as the appearance of 1 or more new lesions and/or unequivocal progression of existing non-target lesions. Target lesions should be selected on the basis of their size (those with the longest diameter) and their suitability for accurate repeated measurements by imaging techniques or clinically. All measurable lesions up to a maximum of 5 lesions per organ and 10 lesions in total, representative of all involved organs, should be identified as target lesions.

  Baseline to data cut-off for analysis of the primary Outcome Measure (up to 3 years, 2 months)

Secondary Outcomes (5)

• Progression-free Survival Within Individual Standard Chemotherapy Cohorts (Taxanes, Gemcitabine, Capecitabine, and Vinorelbine)

  Baseline to data cut-off for analysis of the primary Outcome Measure (up to 3 years, 2 months)

• Overall Survival

  Baseline to the end of the study (up to 6 years, 7 months)

• One-year Survival

  Baseline to the end of the study (up to 6 years, 7 months)

• Objective Response

  Baseline to data cut-off for analysis of the primary Outcome Measure (up to 3 years, 2 months)

• Duration of Objective Response

  Baseline to data cut-off for analysis of the primary Outcome Measure (up to 3 years, 2 months)

Study Arms (2)

Standard chemotherapy + bevacizumab

EXPERIMENTAL

Patients received one of several standard chemotherapies for metastatic breast cancer plus bevacizumab in a dose of either 10 mg/kg intravenously (IV) every 2 weeks or 15 mg/kg IV every 3 weeks depending upon the schedule of chemotherapy chosen.

Drug: Bevacizumab; Drug: Standard chemotherapy

Standard chemotherapy + placebo

PLACEBO COMPARATOR

Patients received one of several standard chemotherapies for metastatic breast cancer plus placebo to bevacizumab administered IV either every 2 weeks or every 3 weeks depending upon the schedule of chemotherapy chosen.

Drug: Placebo; Drug: Standard chemotherapy

Interventions

Bevacizumab DRUG

The dose of bevacizumab was based on a patient's weight at baseline and remained the same throughout the study.

Also known as: Avastin

Standard chemotherapy + bevacizumab

Placebo DRUG

Standard chemotherapy + placebo

Standard chemotherapy DRUG

Patients received one of the following four standard chemotherapies for metastatic breast cancer. 1. Taxane - Paclitaxel (Taxol) 90 mg/m\^2 IV every week for 3 weeks followed by 1 week of rest; paclitaxel (Taxol) 175 mg/m\^2 IV every 3 weeks, or paclitaxel protein-bound particles (Abraxane) 260 mg/m\^2 IV every 3 weeks; or docetaxel (Taxotere) 75-100 mg/m\^2 IV every 3 weeks. 2. Gemcitabine (Gemzar) 1250 mg/m\^2 IV on Days 1 and 8 of each 3-week cycle. 3. Vinorelbine (Navelbine) 30 mg/m\^2 IV every week of each 3-week cycle. 4. Capecitabine (Xeloda) 1000 mg/m\^2 orally twice daily on Days 1-14 of each 3-week cycle.

Standard chemotherapy + bevacizumab; Standard chemotherapy + placebo

Eligibility Criteria

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

You may qualify if:

• Signed informed consent form.
• ≥ 18 years of age.
• Histologically confirmed carcinoma of the breast with measurable or non-measurable metastatic disease that has progressed (patients with a history of brain metastasis are eligible for study participation \[USA only\], as long as their brain metastases have been treated and they have no evidence of progression or hemorrhage after treatment and no ongoing requirement for dexamethasone).
• Progression of disease during or following administration of one (non-investigational) chemotherapy regimen administered in the first-line setting.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• For women of childbearing potential, use of an effective means of non-hormonal contraception.
• Life expectancy ≥ 3 months.
• Willingness and capacity to comply with study and follow-up procedures.

You may not qualify if:

• Prior hormonal therapy only as treatment for metastatic disease without chemotherapy. Patients must have received chemotherapy for their metastatic disease in the first-line setting. Hormone therapy alone is not allowed.
• For subjects who have received prior anthracycline-based therapy, documentation of left ventricular ejection fraction \< 50% by either multiple gated acquisition (MUGA) or echocardiogram (ECHO).
• Treatment with more than one prior cytotoxic regimen for metastatic breast cancer (MBC).
• HER2-positive status (patients who have unknown HER2 status, and for whom determination of HER2 status is not possible, are eligible for this study).
• Unknown estrogen receptor (ER) and progesterone receptor (PR) status.
• Radiation therapy other than for palliation or brain metastasis, biologic therapy, or chemotherapy for MBC within 21 days prior to Day 0 (Day 1 of Cycle 1 of treatment).
• Prior therapy with bevacizumab or other vascular endothelial growth factor (VEGF) pathway-targeted therapy.
• Untreated brain metastasis.
• Inadequately controlled hypertension.
• Unstable angina.
• New York Heart Association Grade II or greater congestive heart failure (CHF).
• History of myocardial infarction within 6 months prior to Day 0 (the day of the first bevacizumab/placebo infusion).
• History of stroke or transient ischemic attack within 6 months prior to Day 0.
• Clinically significant peripheral vascular disease.
• Evidence of bleeding diathesis or coagulopathy.

Sponsors & Collaborators

• Genentech, Inc.: lead

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Bevacizumab

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

Results Point of Contact

• Title: Medical Communications
• Organization: Genentech, Inc.

800 821-8590

Study Officials

• Leo Faoro, MD

  Genentech, Inc.

  STUDY DIRECTOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 23, 2006
• First Posted: January 25, 2006
• Study Start: February 1, 2006
• Primary Completion: March 1, 2009
• Study Completion: September 1, 2012
• Last Updated: July 26, 2013
• Results First Posted: September 24, 2012

Record last verified: 2013-07