Overview

This trial is active, not recruiting.

Condition metastatic breast cancer
Treatments bevacizumab, placebo, chemotherapy
Phase phase 3
Target VEGF
Sponsor Genentech
Start date December 2005
End date July 2008
Trial size 1237 participants
Trial identifier NCT00262067, AVF3694g, BO20094

Summary

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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking double blind (subject, investigator)
Primary purpose treatment
Arm
(Experimental)
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.
bevacizumab Avastin
Patients received bevacizumab until disease progression, treatment limiting toxicity, or death due to any cause up to a maximum treatment duration of 48 months. The dose of bevacizumab was based on the patient's weight at either screening or baseline and remained the same throughout the blinded treatment phase of the study. The initial dose was delivered over 90±10 minutes. If there were no infusion related adverse events (fever and/or chills), the second infusion was delivered over 60±10 minutes. If the 60 minute infusion was well tolerated, all subsequent infusions were delivered over 30±10 minutes.
chemotherapy
The chemotherapy was selected by the investigator prior to randomization. Chemotherapy treatment continued until disease progression, unacceptable toxicity, investigator/patient decision, or death, whichever occurred first, except for the anthracycline-based regimens, which had a maximum treatment duration of 8 cycles. Taxanes - 1 of the following 2 taxanes on Day 1 of every 21-day cycle Docetaxel 75-100 mg/m^2 IV Paclitaxel protein-bound particles (Abraxane®) 260 mg/m^2 IV Anthracyclines - 1 of the following 4 anthracycline-based regimens on Day 1 of every 21-day cycle 5-fluorouracil 500 mg/m^2 IV + epirubicin 90-100 mg/m^2 IV + cyclophosphamide 500 mg/m^2 IV 5-fluorouracil 500 mg/m^2 IV + doxorubicin 50 mg/m^2 IV + cyclophosphamide 500 mg/m^2 IV Doxorubicin 50-60 mg/m^2 IV + cyclophosphamide 500-600 mg/m^2 IV Epirubicin 90-100 mg/m^2 IV + cyclophosphamide 500-600 mg/m^2 IV Capecitabine: 1000 mg/m^2 orally twice daily on Days 1-14 of each 21-day cycle
(Placebo Comparator)
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.
placebo
Placebo consisted of the vehicle for bevacizumab without the antibody.
chemotherapy
The chemotherapy was selected by the investigator prior to randomization. Chemotherapy treatment continued until disease progression, unacceptable toxicity, investigator/patient decision, or death, whichever occurred first, except for the anthracycline-based regimens, which had a maximum treatment duration of 8 cycles. Taxanes - 1 of the following 2 taxanes on Day 1 of every 21-day cycle Docetaxel 75-100 mg/m^2 IV Paclitaxel protein-bound particles (Abraxane®) 260 mg/m^2 IV Anthracyclines - 1 of the following 4 anthracycline-based regimens on Day 1 of every 21-day cycle 5-fluorouracil 500 mg/m^2 IV + epirubicin 90-100 mg/m^2 IV + cyclophosphamide 500 mg/m^2 IV 5-fluorouracil 500 mg/m^2 IV + doxorubicin 50 mg/m^2 IV + cyclophosphamide 500 mg/m^2 IV Doxorubicin 50-60 mg/m^2 IV + cyclophosphamide 500-600 mg/m^2 IV Epirubicin 90-100 mg/m^2 IV + cyclophosphamide 500-600 mg/m^2 IV Capecitabine: 1000 mg/m^2 orally twice daily on Days 1-14 of each 21-day cycle

Primary Outcomes

Measure
Progression-free Survival (PFS) as Determined by the Investigator Using Response Evaluation Criteria in Solid Tumors (RECIST)
time frame: Baseline to the data cut-off date of 31 Jul 2008 (up to 2 years, 7 months)

Secondary Outcomes

Measure
Objective Response as Determined by the Investigator Using Response Evaluation Criteria in Solid Tumors (RECIST)
time frame: Baseline to the data cut-off date of 31 Jul 2008 (up to 2 years, 7 months)
Duration of Objective Response as Determined by the Investigator Using Response Evaluation Criteria in Solid Tumors (RECIST)
time frame: Baseline to the data cut-off date of 31 Jul 2008 (up to 2 years, 7 months)
Overall Survival
time frame: Baseline to the data cut-off of 23 Feb 2009 (up to 3 years, 2 months)
1-year Survival
time frame: Baseline to the data cut-off of 23 Feb 2009 (up to 3 years, 2 months)
Progression-free Survival (PFS) as Determined by the Independent Review Committee Using Response Evaluation Criteria in Solid Tumors (RECIST)
time frame: Baseline to the data cut-off date of 31 Jul 2008 (up to 2 years, 7 months)

Eligibility Criteria

Male or female participants at least 18 years old.

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).

Additional Information

Official title A Multicenter, Phase III, Randomized, Placebo-controlled Trial Evaluating the Efficacy and Safety of Bevacizumab in Combination With Chemotherapy Regimens in Subjects With Previously Untreated Metastatic Breast Cancer
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.
Trial information was received from ClinicalTrials.gov and was last updated in November 2013.
Information provided to ClinicalTrials.gov by Genentech.