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
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Condition or disease | Intervention/treatment | Phase |
---|---|---|
Metastatic Breast Cancer | Drug: Bevacizumab [Avastin] Drug: Paclitaxel Drug: Placebo | Phase 3 |
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 |
Arm | Intervention/treatment |
---|---|
Experimental: A
Paclitaxel + Bevacizumab [Avastin]
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Drug: Bevacizumab [Avastin]
Intravenous repeating dose Drug: Paclitaxel Intravenous repeating dose |
Experimental: B
Paclitaxel + Placebo
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Drug: Paclitaxel
Intravenous repeating dose Drug: Placebo Intravenous repeating dose |
- 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.
- 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.
- 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.
- 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.
- Percentage of Participants Who Died - ITT Population [ Time Frame: From randomization till death or clinical cut-off (up to 244 weeks) ]
- 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.
- 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) ]
- 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.
- 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).
- 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.
- 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.
- 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.
- Percentage of Participants Who Were Alive at 1 Year - ITT Population [ Time Frame: 1 year ]
- Secondary: Percentage of Participants Who Were Alive at 1 Year - High Baseline Plasma VEGF-A ITT Population [ Time Frame: 1 year ]
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Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
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
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
Study Director: | Clinical Trials | Hoffmann-La Roche |
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 |
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 |