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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

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ClinicalTrials.gov Identifier: NCT01186991
Recruitment Status : Completed
First Posted : August 23, 2010
Last Update Posted : January 20, 2017
Sponsor:
Collaborator:
Hoffmann-La Roche
Information provided by (Responsible Party):
Genentech, Inc.

Tracking Information
First Submitted Date  ICMJE August 9, 2010
First Posted Date  ICMJE August 23, 2010
Last Update Posted Date January 20, 2017
Study Start Date  ICMJE March 2011
Actual Primary Completion Date March 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 19, 2017)
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) ]
Original Primary Outcome Measures  ICMJE
 (submitted: August 20, 2010)
Progression-free survival (PFS) or death on study from any cause [ Time Frame: Time from randomization to disease progression or relapse or death from any cause within 30 days of the last study treatment, whichever occurs first. ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 19, 2017)
  • 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) ]
Original Secondary Outcome Measures  ICMJE
 (submitted: August 20, 2010)
  • Objective response [ Time Frame: Complete or partial response maintained ≥ 4 weeks. ]
  • Duration of response [ Time Frame: 24 months ]
  • Overall survival [ Time Frame: 24 months ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study Evaluating the Safety and Efficacy of Onartuzumab And/or Bevacizumab in Combination With Paclitaxel in Participants With Metastatic, Triple Negative Breast Cancer
Official Title  ICMJE 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
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 Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Breast Cancer
Intervention  ICMJE
  • 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
  • Drug: Bevacizumab Placebo
    Placebo matching to bevacizumab will be administered as IV infusion on Day 1 and Day 15 of each 28-day cycle.
  • Drug: Onartuzumab Placebo
    Placebo matching to onartuzumab will be administered as IV infusion on Day 1 and Day 15 of each 28-day cycle.
Study Arms  ICMJE
  • 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).
    Interventions:
    • Drug: Onartuzumab
    • Drug: Bevacizumab
    • Drug: Paclitaxel
  • 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).
    Interventions:
    • Drug: Onartuzumab
    • Drug: Paclitaxel
    • Drug: Bevacizumab Placebo
  • 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).
    Interventions:
    • Drug: Bevacizumab
    • Drug: Paclitaxel
    • Drug: Onartuzumab Placebo
Publications * Diéras V, Campone M, Yardley DA, Romieu G, Valero V, Isakoff SJ, Koeppen H, Wilson TR, Xiao Y, Shames DS, Mocci S, Chen M, Schmid P. Randomized, phase II, placebo-controlled trial of onartuzumab and/or bevacizumab in combination with weekly paclitaxel in patients with metastatic triple-negative breast cancer. Ann Oncol. 2015 Sep;26(9):1904-1910. doi: 10.1093/annonc/mdv263. Epub 2015 Jul 22.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: September 20, 2016)
185
Original Estimated Enrollment  ICMJE
 (submitted: August 20, 2010)
120
Actual Study Completion Date  ICMJE March 2016
Actual Primary Completion Date March 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Belgium,   France,   Germany,   Spain,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01186991
Other Study ID Numbers  ICMJE OAM4861g
GO01334 ( Other Identifier: Hoffmann-La Roche )
2010-020101-32 ( EudraCT Number )
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Genentech, Inc.
Study Sponsor  ICMJE Genentech, Inc.
Collaborators  ICMJE Hoffmann-La Roche
Investigators  ICMJE
Study Director: Clinical Trials Genentech, Inc.
PRS Account Genentech, Inc.
Verification Date January 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP