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Study Evaluating the Safety and Efficacy of Onartuzumab And/or Bevacizumab in Combination With Paclitaxel in Participants With Metastatic, Triple Negative Breast Cancer

This study has been completed.
Sponsor:
Collaborator:
Hoffmann-La Roche
Information provided by (Responsible Party):
Genentech, Inc.
ClinicalTrials.gov Identifier:
NCT01186991
First received: August 9, 2010
Last updated: January 19, 2017
Last verified: January 2017
  Purpose
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).

Condition Intervention Phase
Breast Cancer
Drug: Onartuzumab
Drug: Bevacizumab
Drug: Paclitaxel
Drug: Bevacizumab Placebo
Drug: Onartuzumab Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Participant, Investigator
Primary Purpose: Treatment
Official Title: A Randomized, Phase II, Multicenter, Double-Blind, Placebo-Controlled Study Evaluating the Safety and Efficacy of Onartuzumab And/or Bevacizumab in Combination With Paclitaxel in Patients With Metastatic, Triple-Negative Breast Cancer

Resource links provided by NLM:


Further study details as provided by Genentech, Inc.:

Primary Outcome Measures:
  • 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 [ Time Frame: 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:
  • PFS According to RECIST v1.1 in Participants Who Have not Received Prior Systemic Therapy [ Time Frame: 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) ]
  • Percentage of Participants With Objective Response as Assessed by the Investigator According to RECIST v1.1 [ Time Frame: 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 [ Time Frame: 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) ]
  • Overall Survival (OS) [ Time Frame: 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) ]
  • Percentage of Participants With Adverse Events (AE) and Serious Adverse Events (SAEs) [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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) ]

Enrollment: 185
Study Start Date: March 2011
Study Completion Date: March 2016
Primary Completion Date: March 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Onartuzumab + Bevacizumab + 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).
Drug: Onartuzumab
Onartuzumab will be administered as intravenous (IV) infusion at a dose of 10 milligrams per kilogram (mg/kg) on Day 1 and Day 15 of each 28-day cycle. The dose of onartuzumab will be based on the participant's weight at screening and will remain the same throughout the study.
Other Name: MetMAb
Drug: Bevacizumab
Bevacizumab will be administered as IV infusion at a dose of 10 mg/kg on Day 1 and Day 15 of each 28-day cycle. The dose of bevacizumab will be based on the participant's weight at screening and will remain the same throughout the study.
Other Name: Avastin
Drug: Paclitaxel
Paclitaxel will be administered as IV infusion at a dose of 90 milligrams per meter-squared (mg/m^2) on Day 1, Day 8, and Day 15 of each 28-day cycle.
Other Name: Taxol
Experimental: Onartuzumab + Placebo + 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).
Drug: Onartuzumab
Onartuzumab will be administered as intravenous (IV) infusion at a dose of 10 milligrams per kilogram (mg/kg) on Day 1 and Day 15 of each 28-day cycle. The dose of onartuzumab will be based on the participant's weight at screening and will remain the same throughout the study.
Other Name: MetMAb
Drug: Paclitaxel
Paclitaxel will be administered as IV infusion at a dose of 90 milligrams per meter-squared (mg/m^2) on Day 1, Day 8, and Day 15 of each 28-day cycle.
Other Name: Taxol
Drug: Bevacizumab Placebo
Placebo matching to bevacizumab will be administered as IV infusion on Day 1 and Day 15 of each 28-day cycle.
Active Comparator: Placebo + Bevacizumab + 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).
Drug: Bevacizumab
Bevacizumab will be administered as IV infusion at a dose of 10 mg/kg on Day 1 and Day 15 of each 28-day cycle. The dose of bevacizumab will be based on the participant's weight at screening and will remain the same throughout the study.
Other Name: Avastin
Drug: Paclitaxel
Paclitaxel will be administered as IV infusion at a dose of 90 milligrams per meter-squared (mg/m^2) on Day 1, Day 8, and Day 15 of each 28-day cycle.
Other Name: Taxol
Drug: Onartuzumab Placebo
Placebo matching to onartuzumab will be administered as IV infusion on Day 1 and Day 15 of each 28-day cycle.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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
  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: NCT01186991

  Show 53 Study Locations
Sponsors and Collaborators
Genentech, Inc.
Hoffmann-La Roche
Investigators
Study Director: Clinical Trials Genentech, Inc.
  More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Genentech, Inc.
ClinicalTrials.gov Identifier: NCT01186991     History of Changes
Other Study ID Numbers: OAM4861g
GO01334 ( Other Identifier: Hoffmann-La Roche )
2010-020101-32 ( EudraCT Number )
Study First Received: August 9, 2010
Last Updated: January 19, 2017

Additional relevant MeSH terms:
Breast Neoplasms
Triple Negative Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Bevacizumab
Paclitaxel
Albumin-Bound Paclitaxel
Antibodies, Monoclonal
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
Immunologic Factors

ClinicalTrials.gov processed this record on May 25, 2017