Trial record 1 of 1 for:    NCT01663727
Previous Study | Return to List | Next Study

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 study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT01663727
First received: August 9, 2012
Last updated: January 12, 2016
Last verified: January 2016
  Purpose
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 Intervention Phase
Metastatic Breast Cancer
Drug: Bevacizumab [Avastin]
Drug: Paclitaxel
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, 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

Resource links provided by NLM:


Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:
  • 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) ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline, every 8 weeks until documented disease progression, death or clinical cut-off (up to 117.7 weeks) ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline, every 8 weeks until documented disease progression, death or clinical cut-off (up to 111.3 weeks) ] [ Designated as safety issue: No ]
    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 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) ] [ Designated as safety issue: No ]
    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:
  • Percentage of Participants Who Died - ITT Population [ Time Frame: From randomization till death or clinical cut-off (up to 111.7 weeks) ] [ Designated as safety issue: No ]
  • Overall Survival (OS) - ITT Population [ Time Frame: From randomization till death or clinical cut-off (up to 111.7 weeks) ] [ Designated as safety issue: No ]
    OS was defined as the interval between the date of randomization and death from any cause. OS was estimated using Kaplan Meier method.

  • Percentage of Participants Who Died - High Baseline Plasma VEGF-A ITT Population [ Time Frame: From randomization till death or clinical cut-off (up to 90.9 weeks) ] [ Designated as safety issue: No ]
  • OS - High Baseline Plasma VEGF-A ITT Population [ Time Frame: From randomization till death or clinical cut-off (up to 90.9 weeks) ] [ Designated as safety issue: No ]
    OS was defined as the interval between the date of randomization and death from any cause. OS was estimated using Kaplan Meier method.

  • 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) ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline, every 8 weeks until documented disease progression, death or clinical cut-off (up to 111.3 weeks) ] [ Designated as safety issue: No ]
    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.

  • Duration of Response - ITT Population [ Time Frame: Baseline, every 8 weeks until documented disease progression or clinical cut-off (up to 117.7 weeks) ] [ Designated as safety issue: No ]
    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.

  • 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) ] [ Designated as safety issue: No ]
    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.

  • Percentage of Participants Who Were Alive at 1 Year [ Time Frame: 1 year ] [ Designated as safety issue: No ]

Enrollment: 481
Study Start Date: August 2012
Estimated Study Completion Date: January 2019
Primary Completion Date: November 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01663727

  Show 177 Study Locations
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
Study Director: Clinical Trials Hoffmann-La Roche
  More Information

Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT01663727     History of Changes
Other Study ID Numbers: GO25632  2011-005335-97 
Study First Received: August 9, 2012
Results First Received: January 12, 2016
Last Updated: January 12, 2016
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Bevacizumab
Paclitaxel
Albumin-Bound Paclitaxel
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors
Antineoplastic Agents
Antineoplastic Agents, Phytogenic
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on August 25, 2016