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Completed

NCT Number: NCT01663727

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

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.

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Key information

Conditions

Metastatic Breast Cancer Breast Diseases Breast Neoplasms Neoplasms Neoplasms by Site Skin Diseases Skin and Connective Tissue Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

Hospital Britanico de Buenos Aires, Ciudad Autonoma Buenos Aires, Argentina

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

bevacizumab [Avastin]

Drug

Intravenous repeating dose

paclitaxel

Drug

Intravenous repeating dose

Placebo

Drug

Intravenous repeating dose

Primary outcomes

  1. Percentage of Participants With Progression or Death in Intent-to-Treat (ITT) Population

    Time frame: 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.

  2. Progression Free Survival (PFS) in ITT Population

    Time frame: 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.

  3. Percentage of Participants With Progression or Death in High Baseline Plasma Vascular Endothelial Growth Factor-A (VEGF-A) ITT Population

    Time frame: 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.

  4. PFS in High Baseline Plasma VEGF-A ITT Population

    Time frame: 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.

Secondary outcomes

  1. Percentage of Participants Who Died - ITT Population

    Time frame: From randomization till death or clinical cut-off (up to 244 weeks)

  2. Overall Survival (OS) - ITT Population

    Time frame: 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.

  3. Percentage of Participants Who Died - High Baseline Plasma VEGF-A ITT Population

    Time frame: From randomization till death or clinical cut-off (up to 244 weeks)

  4. OS - High Baseline Plasma VEGF-A ITT Population

    Time frame: 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.

  5. Percentage of Participants With an Objective Response - ITT Population

    Time frame: 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).

  6. Percentage of Participants With an Objective Response - High Baseline Plasma VEGF-A ITT Population

    Time frame: 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.

  7. Duration of Response - ITT Population

    Time frame: 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.

  8. Duration of Response - High Baseline Plasma VEGF-A ITT Population

    Time frame: 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.

  9. Percentage of Participants Who Were Alive at 1 Year - ITT Population

    Time frame: 1 year

  10. Secondary: Percentage of Participants Who Were Alive at 1 Year - High Baseline Plasma VEGF-A ITT Population

    Time frame: 1 year

Sponsors and collaborators

Lead sponsor

Hoffmann-La Roche

Industry

Registry information

Official study title

A Phase III, Randomized, Double-Blind, Placebo-Controlled, Multicenter 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

Important dates

Study start
2012
Primary completion
2014
Study completion
2017
First posted
Aug 13, 2012
Registry last updated
Jan 22, 2019

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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