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
Trial Snapshot
- Phase
- Phase 2
- Status
- Completed
- Sponsor
- Genentech, Inc.
- Enrollment
- 185
- Locations
- 53
- Primary Endpoint
- 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
Study Overview
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).
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Double (Participant, Investigator)
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- Female
- Accepts Healthy Volunteers
- No
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
Arms & Interventions
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).
Intervention: Onartuzumab (Drug)
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).
Intervention: Bevacizumab (Drug)
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).
Intervention: Paclitaxel (Drug)
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).
Intervention: Onartuzumab (Drug)
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).
Intervention: Paclitaxel (Drug)
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).
Intervention: Bevacizumab Placebo (Drug)
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).
Intervention: Bevacizumab (Drug)
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).
Intervention: Paclitaxel (Drug)
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).
Intervention: Onartuzumab Placebo (Drug)
Outcomes
Primary Outcomes
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 Outcomes
- 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))