Study Evaluating the Safety and Efficacy of Onartuzumab And/or Bevacizumab in Combination With Paclitaxel in Participants With Metastatic, Triple Negative Breast Cancer
- Conditions
- Breast Cancer
- Interventions
- Registration Number
- NCT01186991
- Lead Sponsor
- Genentech, Inc.
- Brief Summary
This is a randomized, Phase II, double-blind, multicenter, placebo-controlled trial designed to preliminarily estimate the efficacy and evaluate the safety and tolerability of onartuzumab (MetMAb) + bevacizumab + paclitaxel and onartuzumab + placebo + paclitaxel versus placebo + bevacizumab + paclitaxel in participants with metastatic or locally recurrent, triple-negative breast cancer who either have not received treatment (first-line) or have progressed after one conventional cytotoxic chemotherapy regimen (second-line).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Female
- Target Recruitment
- 185
- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
- Histologically confirmed estrogen receptor (ER)-, progesterone receptor (PR)-, and human epidermal growth factor 2 (HER2)-negative (triple-negative) adenocarcinoma of the breast
- Confirmed availability of tumor tissue
- Prior therapy with two or more regimens for metastatic breast cancer
- Any systemic anti-cancer therapy within 3 weeks prior to Day 1 of Cycle 1
- Major surgical procedure, open biopsy, or significant traumatic injury within 30 days prior to Day 1 of Cycle 1
- Prior therapy with a taxane for metastatic breast cancer
- Prior therapy with bevacizumab, sorafenib, sunitinib, or other putative vascular endothelial growth factor (VEGF) pathway-targeted therapy following diagnosis of breast cancer
- Prior therapy with hormones and/or trastuzumab
- Inadequate hematology, renal, or hepatic organ function
Bevacizumab Exclusion Criteria:
- Uncontrolled hypertension (systolic pressure greater than [>] 150 millimeters of mercury [mmHg] and/or diastolic pressure > 100 mmHg), with or without anti-hypertensive medication
- Evidence of bleeding diathesis or coagulopathy
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Onartuzumab + Bevacizumab + Paclitaxel Bevacizumab Participants will receive treatment with onartuzumab, bevacizumab, and paclitaxel, which may continue until disease progression, unacceptable drug-related toxicity, investigator decision, death, or completion of study, whichever occurs first (up to approximately 5 years). Onartuzumab + Bevacizumab + Paclitaxel Paclitaxel Participants will receive treatment with onartuzumab, bevacizumab, and paclitaxel, which may continue until disease progression, unacceptable drug-related toxicity, investigator decision, death, or completion of study, whichever occurs first (up to approximately 5 years). Onartuzumab + Placebo + Paclitaxel Bevacizumab Placebo Participants will receive treatment with onartuzumab, placebo matching to bevacizumab, and paclitaxel, which may continue until disease progression, unacceptable toxicity, investigator decision, death, or completion of study, whichever occurs first (up to approximately 5 years). Placebo + Bevacizumab + Paclitaxel Onartuzumab Placebo Participants will receive treatment with placebo matching to onartuzumab, bevacizumab, and paclitaxel, which may continue until disease progression, unacceptable toxicity, investigator decision, death, or completion of study, whichever occurs first (up to approximately 5 years). Onartuzumab + Placebo + Paclitaxel Paclitaxel Participants will receive treatment with onartuzumab, placebo matching to bevacizumab, and paclitaxel, which may continue until disease progression, unacceptable toxicity, investigator decision, death, or completion of study, whichever occurs first (up to approximately 5 years). Placebo + Bevacizumab + Paclitaxel Bevacizumab Participants will receive treatment with placebo matching to onartuzumab, bevacizumab, and paclitaxel, which may continue until disease progression, unacceptable toxicity, investigator decision, death, or completion of study, whichever occurs first (up to approximately 5 years). Placebo + Bevacizumab + Paclitaxel Paclitaxel Participants will receive treatment with placebo matching to onartuzumab, bevacizumab, and paclitaxel, which may continue until disease progression, unacceptable toxicity, investigator decision, death, or completion of study, whichever occurs first (up to approximately 5 years). Onartuzumab + Bevacizumab + Paclitaxel Onartuzumab Participants will receive treatment with onartuzumab, bevacizumab, and paclitaxel, which may continue until disease progression, unacceptable drug-related toxicity, investigator decision, death, or completion of study, whichever occurs first (up to approximately 5 years). Onartuzumab + Placebo + Paclitaxel Onartuzumab Participants will receive treatment with onartuzumab, placebo matching to bevacizumab, and paclitaxel, which may continue until disease progression, unacceptable toxicity, investigator decision, death, or completion of study, whichever occurs first (up to approximately 5 years).
- Primary Outcome Measures
Name Time Method Progression-free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) in Participants Who Have not Received Prior Systemic Therapy or Have Progressed to Prior First-line Treatment From randomization until disease progression (PD), relapse, or death on study (within 30 days of last study drug administration) from any cause, whichever occurs first (to be assessed according to local standard of care overall up to 5 years)
- Secondary Outcome Measures
Name Time Method Percentage of Participants With Objective Response as Assessed by the Investigator According to RECIST v1.1 From randomization until PD, relapse, or death on study from any cause, whichever occurs first (to be assessed according to local standard of care overall up to 5 years) Overall Survival (OS) From randomization until death from any cause, loss to follow-up, study termination by sponsor, or participant's withdrawal in survival follow-up (overall up to 5 years) PFS According to RECIST v1.1 in Participants Who Have not Received Prior Systemic Therapy From randomization until PD, relapse, or death on study from any cause, whichever occurs first (to be assessed according to local standard of care overall up to 5 years) Duration of Response as Assessed by the Investigator Using RECIST v1.1 From initial objective response to PD or death on study from any cause, whichever occurs first (to be assessed according to local standard of care overall up to 5 years) Percentage of Participants With Adverse Events (AE) and Serious Adverse Events (SAEs) Day 1 Cycle 1 (cycle length=28 days) up to 30 days after last dose of study drug or study discontinuation/termination, whichever is later (overall up to 5 years) Number of Cycles of Treatment Received for Onartuzumab, Paclitaxel, and Bevacizumab During the Study Day 1 Cycle 1 (cycle length=28 days) up to last dose of study drug or study discontinuation/termination, whichever is later (overall up to 5 years) Percentage of Participants With Anti-therapeutic Antibodies (ATAs) Against Onartuzumab Predose on Day 1 of Cycles 1-4 (cycle length=28 days), 30 days after last administration of onartuzumab or initiation of another therapy (overall up to 5 years) Serum Levels of ATAs Against Onartuzumab Predose on Day 1 of Cycles 1-4 (cycle length=28 days), 30 days after last administration of onartuzumab or initiation of another therapy (overall up to 5 years)
Trial Locations
- Locations (53)
Can Care Assoc Med Group Inc; Beach Cities Offices
🇺🇸Los Angeles, California, United States
Comprehensive Blood/Cancer Ctr
🇺🇸Bakersfield, California, United States
St. Jude Heritage Healthcare; Virgiia K.Crosson Can Ctr
🇺🇸Fullerton, California, United States
Univ of California Los Angeles
🇺🇸Los Angeles, California, United States
Kaiser Permanente - Vallejo
🇺🇸Vallejo, California, United States
Holy Cross Hospital
🇺🇸Fort Lauderdale, Florida, United States
AZ Sint Lucas (Sint Lucas)
🇧🇪Gent, Belgium
Sint Augustinus Wilrijk
🇧🇪Wilrijk, Belgium
CH Jolimont - Lobbes (Jolimont)
🇧🇪Haine-Saint-Paul, Belgium
Magee Womens Hospital
🇺🇸Pittsburgh, Pennsylvania, United States
Cancer Center of Kansas
🇺🇸Wichita, Kansas, United States
Sharp Healthcare; Oncology Research Program
🇺🇸San Diego, California, United States
Duke University Medical Center
🇺🇸Durham, North Carolina, United States
Mount Vernon Hospital; Centre For Cancer Treatment
🇬🇧Northwood, United Kingdom
Christie Hospital NHS Trust
🇬🇧Manchester, United Kingdom
Universitätsklinik Tübingen; Frauenklinik
🇩🇪Tübingen, Germany
Suburban Hematology Oncology
🇺🇸Lawrenceville, Georgia, United States
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
Florida Cancer Specialists; SCRI
🇺🇸Fort Myers, Florida, United States
North Shore Hem Onc Associates
🇺🇸East Setauket, New York, United States
Karmanos Cancer Institute..
🇺🇸Detroit, Michigan, United States
South Carolina Onc. Associate
🇺🇸Columbia, South Carolina, United States
Comprehensive Cancer Centers of Nevada
🇺🇸Las Vegas, Nevada, United States
SCRI Tennessee Oncology Chattanooga
🇺🇸Chattanooga, Tennessee, United States
The Sarah Cannon Research Inst
🇺🇸Nashville, Tennessee, United States
Northern Utah Associates
🇺🇸Ogden, Utah, United States
Institut Jules Bordet
🇧🇪Bruxelles, Belgium
UZ Antwerpen
🇧🇪Edegem, Belgium
Jessa Zkh (Campus Virga Jesse)
🇧🇪Hasselt, Belgium
CHU Sart-Tilman
🇧🇪Liège, Belgium
Centre Francois Baclesse; Gastro-Enterologie
🇫🇷Caen, France
Centre Leon Berard
🇫🇷Lyon, France
Centre Georges Francois Leclerc; Oncologie 3
🇫🇷Dijon, France
Institut Bergonie; Oncologie
🇫🇷Bordeaux, France
Institut Curie; Oncologie Medicale
🇫🇷Paris, France
Institut régional du Cancer Montpellier
🇫🇷Montpellier, France
Ico Rene Gauducheau; Oncologie
🇫🇷Saint Herblain, France
Centre Rene Huguenin; CONSULT SPECIALISEES
🇫🇷St Cloud, France
Institut Claudius Regaud; Departement Oncologie Medicale
🇫🇷Toulouse, France
Praxis Dr. med. Klausmann; SHOD
🇩🇪Aschaffenburg, Germany
Klinikum rechts der Isar der TU München; Frauenklinik
🇩🇪Muenchen, Germany
Klinik Johann Wolfgang von Goethe Uni
🇩🇪Frankfurt am Main, Germany
Hospital Universitario Puerta del Mar; Servicio de Oncologia
🇪🇸Cádiz, Cadiz, Spain
Hospital Universitario Puerta de Hierro
🇪🇸Majadahonda, Madrid, Spain
Centro Oncológico Gallego José Antonio Quiroga y Piñeiro, Servicio de Oncologia
🇪🇸La Coruña, Spain
Hospital Univ Vall d'Hebron; Servicio de Oncologia
🇪🇸Barcelona, Spain
Brighton and Sussex Univ Hosp
🇬🇧Brighton, United Kingdom
Instituto Catalán de OncologÃa; Servicio de Farmacia
🇪🇸Barcelona, Spain
Nottingham City Hospital; Oncology
🇬🇧Nottingham, United Kingdom
The Clatterbridge Cancer Ctr For Oncolgy
🇬🇧Wirral, United Kingdom
MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
Kaiser Permanente Sacramento Medical Center
🇺🇸Sacramento, California, United States
Charleston Hematology Oncology
🇺🇸Charleston, South Carolina, United States