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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

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ClinicalTrials.gov Identifier: NCT01663727
Recruitment Status : Completed
First Posted : August 13, 2012
Results First Posted : February 10, 2016
Last Update Posted : January 22, 2019
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

Study Description
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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.

Condition or disease Intervention/treatment Phase
Metastatic Breast Cancer Drug: Bevacizumab [Avastin] Drug: Paclitaxel Drug: Placebo Phase 3

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 481 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official 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
Actual Study Start Date : August 27, 2012
Actual Primary Completion Date : November 30, 2014
Actual Study Completion Date : November 21, 2017

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

Arms and Interventions
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Arm Intervention/treatment
Experimental: A
Paclitaxel + Bevacizumab [Avastin]
 Drug: Bevacizumab [Avastin]
Intravenous repeating dose

Drug: Paclitaxel
Intravenous repeating dose
Experimental: B
Paclitaxel + Placebo
 Drug: Paclitaxel
Intravenous repeating dose

Drug: Placebo
Intravenous repeating dose


Outcome Measures
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Primary Outcome Measures :
  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 Outcome Measures :
  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 ]

Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01663727


Locations
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Sponsors and Collaborators
Hoffmann-La Roche
Investigators
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Study Director: Clinical Trials Hoffmann-La Roche
More Information
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Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT01663727    
Other Study ID Numbers: GO25632
2011-005335-97 ( EudraCT Number )
First Posted: August 13, 2012    Key Record Dates
Results First Posted: February 10, 2016
Last Update Posted: January 22, 2019
Last Verified: January 2019
Additional relevant MeSH terms:
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Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Paclitaxel
Bevacizumab
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
 Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Immunological
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors