A Study Evaluating the Efficacy and Safety of Bevacizumab in Combination With Chemotherapy in Untreated Metastatic Breast Cancer (RIBBON 1)

Genentech

Status and phase: Unknown; Phase 3

Conditions: Metastatic Breast Cancer

Treatments: Drug: Placebo; Drug: Bevacizumab; Drug: Chemotherapy

Study type: Interventional

Funder types: Industry

Identifiers

NCT00262067

BO20094 (Other Identifier)

AVF3694g

Details and patient eligibility

About

This is a Phase III, multicenter, randomized, placebo-controlled trial designed to evaluate the efficacy and safety of bevacizumab in combination with chemotherapy compared with chemotherapy alone in subjects with previously untreated metastatic breast cancer.

Full description

This study includes a blinded treatment phase, an optional open-label post-progression phase, and a survival follow-up phase. During the blinded treatment phase, patients receive chemotherapy and study drug (bevacizumab or placebo) every 3 weeks until disease progression, treatment-limiting toxicity, or death due to any cause. The optional open-label post-progression phase consists of chemotherapy treatment (per investigator discretion) and optional treatment with open-label bevacizumab. Patients who complete the study or who discontinue from treatment (regardless of participation in the optional open-label post-progression phase) will be followed for survival and subsequent anti-cancer therapies every 4 months until death, withdrawal of consent, loss to follow-up, or study termination. Patients who discontinue from treatment during the blinded treatment phase for reasons other than disease progression will have tumor assessments every 9 weeks until documented disease progression or death.

Enrollment: 1,237 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Histologically or cytologically confirmed adenocarcinoma of the breast, with measurable or non-measurable locally recurrent or metastatic disease.
• Signed Informed Consent Form.
• Age ≥ 18 years.
• For women of childbearing potential, use of accepted and effective method of non-hormonal contraception.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Ability and capacity to comply with study and follow-up procedures.
• For anthracycline cohort only: Adequate left ventricular function at study entry, defined as a left ventricular ejection fraction (LVEF) ≥ 50% by either multigated acquisition (MUGA) scan scan or echocardiography (ECHO).
• For subjects who have received recent radiation therapy, recovery prior to baseline (Day 0) from any significant (Grade ≥ 3) acute toxicity.

Exclusion criteria

• Unknown human epidermal growth factor receptor 2 (HER2) status or known HER2-positive status.
• Prior chemotherapy for locally recurrent or metastatic disease.
• Prior hormonal therapy less than 1 week prior to Day 0.
• Prior adjuvant or neoadjuvant chemotherapy within 12 months prior to Day 0.
• For anthracycline cohort only: Prior anthracycline as part of neoadjuvant or adjuvant therapy for localized breast cancer.
• Investigational therapy within 28 days of Day 0.
• Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to Day 0, or anticipation of need for major surgical procedure during the course of the study.
• Minor surgical procedures, such as fine needle aspirations or core biopsies, within 7 days prior to Day 0.
• Prior therapy with bevacizumab, sorafenib, sunitinib, or other vascular endothelial growth factor (VEGF) pathway-targeted therapy.
• Known brain or other central nervous system (CNS) metastases.
• Blood pressure of > 150/100 mmHg.
• Unstable angina.
• New York Heart Association (NYHA) Grade II or greater congestive heart failure (CHF).
• History of myocardial infarction within 6 months prior to Day 0.
• 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.
• 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.
• Pregnancy (positive serum pregnancy test) or lactation.
• Inadequate organ function, as evidenced by any of the following laboratory values: Absolute neutrophil count < 1500/uL; platelet count < 100,000/uL; total bilirubin > 1.5 mg/dL; alkaline phosphatase, AST, and/or ALT > 2x upper limit of normal (ULN) (> 5x ULN in subjects with known liver or, for alkaline phosphatase elevations, bone involvement); alkaline phosphatase > 2x ULN (> 7x ULN in subjects with known bone involvement); serum creatinine > 2.0 mg/dL; partial thromboplastin time (PTT) and/or either international normalized ratio (INR) or prothrombin time (PT) > 1.5x upper limit of normal (except for subjects receiving anti-coagulation therapy); urine protein/creatinine ratio > 1.0 at screening for U.S. subjects, or urine dipstick for proteinuria >/= 1+ at screening followed by 24-hour urine collection demonstrating > 1 g protein/24 hr for ex-U.S. subjects.
• Uncontrolled serious medical or psychiatric illness.
• Active infection requiring intravenous (iv) antibiotics at Day 0.
• 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 (subjects with a history of bilateral breast cancer will be eligible).

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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1,237 participants in 2 patient groups, including a placebo group

Bevacizumab + chemotherapy

Experimental group

Description:

Patients received bevacizumab 15 mg/kg intravenously (IV) on Day 1 of every 21-day cycle plus one of several standard chemotherapies (taxanes, anthracycline-based regimens, or capecitabine) for metastatic breast cancer.

Treatment:

Drug: Chemotherapy

Drug: Bevacizumab

Placebo + chemotherapy

Placebo Comparator group

Description:

Patients received placebo to bevacizumab administered IV on Day 1 of every 21-day cycle + 1 of several standard chemotherapies (taxanes, anthracycline-based regimens, or capecitabine) for metastatic breast cancer.

Treatment:

Drug: Chemotherapy

Drug: Placebo