Study To Evaluate the Efficacy and Safety Of Bevacizumab, and Associated Biomarkers, In Combination With Paclitaxel Compared With Paclitaxel Plus Placebo as First-line Treatment Of Patients With Her2-Negative Metastatic Breast Cancer

Phase 3

Completed

Conditions: Metastatic Breast Cancer

Interventions: Drug: Bevacizumab [Avastin]
Drug: Paclitaxel
Drug: Placebo

Registration Number: NCT01663727

Lead Sponsor: Hoffmann-La Roche

Brief Summary: This is a Phase III, randomized, double-blind, placebo-controlled multicenter study to evaluate the efficacy and safety of bevacizumab administered in combination with paclitaxel in patients with previously untreated, locally recurrent, or metastatic HER2-negative breast cancer. Patients will be randomized to one of two treatment arms: bevacizumab or placebo. All patients will be given an intravenous (IV) infusion of of paclitaxel (90 mg/m2) for 3 weeks during each 28-day cycle. bevacizumab or placebo (10 mg/kg) will be administered by IV infusion on Days 1 and 15 of each 28-day cycle. Patients will be treated until disease progression, unacceptable toxicity or death from any cause occurs.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 481

Inclusion Criteria

Histologically or cytologically confirmed, HER2-negative adenocarcinoma of the breast, with measurable or non-measurable locally recurrent or metastatic disease. Locally recurrent disease must not be amenable to resection with curative intent.
ECOG performance status of 0 or 1
For women of childbearing potential, use of an acceptable and effective method of non-hormonal contraception
For patients who have received recent radiotherapy, recovery prior to randomization from any significant acute toxicity, and radiation treatments have to be completed more than 3 weeks from randomization

Exclusion Criteria

Disease-Specific Exclusions:

HER2-positive status
Prior chemotherapy for locally recurrent or metastatic disease
Prior hormonal therapy < 2 weeks prior to randomization
Prior adjuvant or neo-adjuvant chemotherapy is allowed, provided its conclusion has been for at least 12 months prior to randomization
Investigational therapy within 28 days of randomization

General Medical Exclusions:

Life expectancy of < 12 weeks
Inadequate organ function
Uncontrolled serious medical or psychiatric illness
Active infection requiring intravenous (IV) antibiotics at screening
Pregnancy or lactation
History of other malignancies within 5 years prior to screening, except for tumors with a negligible risk for metastasis or death

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
A	Bevacizumab [Avastin]	Paclitaxel + Bevacizumab \[Avastin\]
B	Paclitaxel	Paclitaxel + Placebo
B	Placebo	Paclitaxel + Placebo
A	Paclitaxel	Paclitaxel + Bevacizumab \[Avastin\]

Primary Outcome Measures

Name	Time	Method
Percentage of Participants With Progression or Death in Intent-to-Treat (ITT) Population	Baseline, every 8 weeks until documented disease progression, death or clinical cut-off (up to 117.7 weeks)	Tumor assessment was performed as per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) by investigator. Disease progression was defined as at least 20 percent (%) increase in the sum of diameters of target lesions compared to smallest sum of diameters on-study and absolute increase of at least 5 millimeter (mm), unequivocal progression of existing non-target lesions, or presence of new lesions.
Progression Free Survival (PFS) in ITT Population	Baseline, every 8 weeks until documented disease progression, death or clinical cut-off (up to 117.7 weeks)	PFS was defined as the interval between the date of randomization and the first documentation of progressive disease or death from any cause. Tumor assessment was performed as per RECIST v1.1 by investigator. Disease progression was defined as at least 20% increase in the sum of diameters of target lesions compared to smallest sum of diameters on-study and absolute increase of at least 5 mm, unequivocal progression of existing non-target lesions, or presence of new lesions. PFS was estimated using Kaplan Meier method.
PFS in High Baseline Plasma VEGF-A ITT Population	Baseline, every 8 weeks until documented disease progression, death or clinical cut-off (up to 111.3 weeks)	PFS was defined as the interval between the date of randomization and the first documentation of progressive disease or death from any cause. Tumor assessment was performed as per RECIST v1.1 by investigator. Disease progression was defined as at least 20% increase in the sum of diameters of target lesions compared to smallest sum of diameters on-study and absolute increase of at least 5 mm, unequivocal progression of existing non-target lesions, or presence of new lesions. PFS was estimated using Kaplan Meier method.
Percentage of Participants With Progression or Death in High Baseline Plasma Vascular Endothelial Growth Factor-A (VEGF-A) ITT Population	Baseline, every 8 weeks until documented disease progression, death or clinical cut-off (up to 111.3 weeks)	Tumor assessment was performed as per RECIST v1.1 by investigator. Disease progression was defined as at least 20% increase in the sum of diameters of target lesions compared to smallest sum of diameters on-study and absolute increase of at least 5 mm, unequivocal progression of existing non-target lesions, or presence of new lesions.

Secondary Outcome Measures

Name	Time	Method
Percentage of Participants Who Died - ITT Population	From randomization till death or clinical cut-off (up to 244 weeks)
Percentage of Participants With an Objective Response - ITT Population	Baseline, every 8 weeks until documented disease progression, death or clinical cut-off (up to 117.7 weeks)	Objective response was defined as having a Complete Response (CR) or Partial Response (PR) according to a RECIST criteria v 1.1. CR was defined as disappearance of all target and non-target lesions and no new lesions, all pathological lymph nodes must have decreased to \<10 mm in short axis and normalization of tumor marker level. PR was defined as at least a 30% decrease in the sum of diameters of target lesions (taking as reference the baseline sum diameters), no progression in non-target lesions, and no new lesions. Measurable disease was defined by the presence of at least one measurable lesion by clinical measurement, chest x-ray, computed tomography (CT), or magnetic resonance imaging (MRI).
Percentage of Participants With an Objective Response - High Baseline Plasma VEGF-A ITT Population	Baseline, every 8 weeks until documented disease progression, death or clinical cut-off (up to 111.3 weeks)	Objective response was defined as having a CR or PR according to a RECIST criteria v 1.1. CR was defined as disappearance of all target and non-target lesions and no new lesions, all pathological lymph nodes must have decreased to \<10 mm in short axis and normalization of tumor marker level. PR was defined as at least a 30% decrease in the sum of diameters of target lesions (taking as reference the baseline sum diameters), no progression in non-target lesions, and no new lesions. Measurable disease was defined by the presence of at least one measurable lesion by clinical measurement, chest x-ray, CT, or MRI.
Overall Survival (OS) - ITT Population	From randomization till death or clinical cut-off (up to 244 weeks)	OS was defined as the interval between the date of randomization and death from any cause. OS was estimated using Kaplan Meier method.
Secondary: Percentage of Participants Who Were Alive at 1 Year - High Baseline Plasma VEGF-A ITT Population	1 year
Percentage of Participants Who Died - High Baseline Plasma VEGF-A ITT Population	From randomization till death or clinical cut-off (up to 244 weeks)
OS - High Baseline Plasma VEGF-A ITT Population	From randomization till death or clinical cut-off (up to 244 weeks)	OS was defined as the interval between the date of randomization and death from any cause. OS was estimated using Kaplan Meier method.
Duration of Response - ITT Population	Baseline, every 8 weeks until documented disease progression or clinical cut-off (up to 117.7 weeks)	Duration of response was defined as the time from the initial date of the objective response to documented disease progression or death (whichever occurred first). Objective response was defined as having a CR or PR according to a RECIST criteria v 1.1. CR was defined as disappearance of all target and non-target lesions and no new lesions, all pathological lymph nodes must have decreased to \<10 mm in short axis and normalization of tumor marker level. PR was defined as at least a 30% decrease in the sum of diameters of target lesions (taking as reference the baseline sum diameters), no progression in non-target lesions, and no new lesions. Disease progression was defined as at least 20% increase in the sum of diameters of target lesions compared to smallest sum of diameters on-study and absolute increase of at least 5 mm, unequivocal progression of existing non-target lesions, or presence of new lesions. Analysis was performed using Kaplan Meier method.
Percentage of Participants Who Were Alive at 1 Year - ITT Population	1 year
Duration of Response - High Baseline Plasma VEGF-A ITT Population	Baseline, every 8 weeks until documented disease progression or clinical cut-off (up to 111.3 weeks)	Duration of response was defined as the time from the initial date of the objective response to documented disease progression or death (whichever occurred first). Objective response was defined as having a CR or PR according to a RECIST criteria v 1.1. CR was defined as disappearance of all target and non-target lesions and no new lesions, all pathological lymph nodes must have decreased to \<10 mm in short axis and normalization of tumor marker level. PR was defined as at least a 30% decrease in the sum of diameters of target lesions (taking as reference the baseline sum diameters), no progression in non-target lesions, and no new lesions. Disease progression was defined at least 20% increase in the sum of diameters of target lesions compared to smallest sum of diameters on-study and absolute increase of at least 5 mm, unequivocal progression of existing non-target lesions, or presence of new lesions. Analysis was performed using Kaplan Meier method.

Trial Locations

Locations (173): University of Alabama at Birmingham
🇺🇸
Birmingham, Alabama, United States
Arizona Cancer Center
🇺🇸
Tucson, Arizona, United States
Wilshire Oncology Medical Group
🇺🇸
West Covina, California, United States
Long Beach Memorial Medical Center; Oncology
🇺🇸
Long Beach, California, United States
Tenet Health System Desert Inc
🇺🇸
Palm Springs, California, United States
Wilshire Oncology Medical Group; Oncology
🇺🇸
Pomona, California, United States
Washington Hospital
🇺🇸
Washington, District of Columbia, United States
Sylvester Comprehensive Cancer Center - Deerfield Beach; Sylvester Cancer Center
🇺🇸
Deerfield Beach, Florida, United States
Florida Cancer Specialists - Broadway
🇺🇸
Fort Myers, Florida, United States
BRCR Medical Center, Inc.
🇺🇸
Plantation, Florida, United States
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University of Alabama at Birmingham
🇺🇸Birmingham, Alabama, United States