A Study to Evaluate the Safety and Efficacy of Bevacizumab in Combination With Chemotherapy in Previously Treated Metastatic Breast Cancer (RIBBON 2)
Condition: Metastatic Breast Cancer
MeSH terms: Breast Neoplasms
Intervention: Bevacizumab; Placebo; Standard chemotherapy
Intervention description: The dose of bevacizumab was based on a patient's weight at baseline and remained the same throughout the study.; Patients received one of the following four standard chemotherapies for metastatic breast cancer.
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.
Gemcitabine (Gemzar) 1250 mg/m^2 IV on Days 1 and 8 of each 3-week cycle.
Vinorelbine (Navelbine) 30 mg/m^2 IV every week of each 3-week cycle.
Capecitabine (Xeloda) 1000 mg/m^2 orally twice daily on Days 1-14 of each 3-week cycle.
Intervention MeSH terms: Bevacizumab
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 684.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Ribbon 2; Avastin; MBC; Breast cancer

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.
    

Eligibility criteria:

        Inclusion Criteria:

          -  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.

        Exclusion Criteria:

          -  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.

          -  Major surgical procedure, open biopsy, or significant traumatic injury within 28 days
             prior to Day 0; anticipation of need for major elective surgical procedure during the
             study.

          -  Minor surgical procedures, fine-needle aspirations, or core biopsies within 7 days
             prior to Day 0.

          -  History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess
             within 6 months prior to Day 0.

          -  Serious, non-healing wound, ulcer, or bone fracture.

          -  History of anaphylactic reaction to monoclonal antibody therapy not controlled with
             treatment premedication.

          -  History of other malignancies within 5 years of Day 0, except for tumors with a
             negligible risk for metastasis or death, such as adequately controlled basal cell
             carcinoma or squamous cell carcinoma of the skin or carcinoma in situ of the cervix.

          -  inadequate organ function.

          -  Pregnancy (positive serum pregnancy test) or lactation.

          -  Any other diseases, metabolic dysfunction, physical examination finding, or clinical
             laboratory finding giving reasonable suspicion of a disease or condition that
             contraindicates the use of an investigational drug or that may affect the
             interpretation of the results or renders the subject at high risk from treatment
             complications.