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

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

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 Overview

• Status: Completed
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: Onartuzumab; Drug: Bevacizumab; Drug: Paclitaxel; Drug: Bevacizumab Placebo; Drug: Onartuzumab Placebo

• Study Type: Interventional
• Enrollment (Actual): 185
• Phase: Phase 2

Contacts and Locations

Study Locations

• Belgium
  • Bruxelles, Belgium, 1000
    • Institut Jules Bordet
  • Edegem, Belgium, 2650
    • UZ Antwerpen
  • Gent, Belgium, 9000
    • AZ Sint Lucas (Sint Lucas)
  • Haine-Saint-Paul, Belgium, 7100
    • CH Jolimont - Lobbes (Jolimont)
  • Hasselt, Belgium, 3500
    • Jessa Zkh (Campus Virga Jesse)
  • Liège, Belgium, 4000
    • CHU Sart-Tilman
  • Wilrijk, Belgium, 2610
    • Sint Augustinus Wilrijk
• France
  • Bordeaux, France, 33076
    • Institut Bergonie; Oncologie
  • Caen, France, 14076
    • Centre Francois Baclesse; Gastro-Enterologie
  • Dijon, France, 21079
    • Centre Georges Francois Leclerc; Oncologie 3
  • Lyon, France, 69008
    • Centre Léon Bérard
  • Montpellier, France, 34298
    • Institut régional du Cancer Montpellier
  • Paris, France, 75231
    • Institut Curie; Oncologie Medicale
  • Saint Herblain, France, 44805
    • Ico Rene Gauducheau; Oncologie
  • St Cloud, France, 92210
    • Centre Rene Huguenin; CONSULT SPECIALISEES
  • Toulouse, France, 31059
    • Institut Claudius Regaud; Departement Oncologie Medicale
• Germany
  • Aschaffenburg, Germany, 63739
    • Praxis Dr. med. Klausmann; SHOD
  • Frankfurt am Main, Germany, 60590
    • Klinik Johann Wolfgang von Goethe Uni
  • Muenchen, Germany, 81675
    • Klinikum rechts der Isar der TU München; Frauenklinik
  • Tübingen, Germany, 72076
    • Universitätsklinik Tübingen; Frauenklinik
• Spain
  • Barcelona, Spain, 08035
    • Hospital Univ Vall d'Hebron; Servicio de Oncologia
  • Barcelona, Spain, 08907
    • Instituto Catalán de Oncología; Servicio de Farmacia
  • La Coruña, Spain, 15009
    • Centro Oncológico Gallego José Antonio Quiroga y Piñeiro, Servicio de Oncologia
  • Cadiz
    • Cádiz, Cadiz, Spain, 11009
      • Hospital Universitario Puerta del Mar; Servicio de Oncologia
  • Madrid
    • Majadahonda, Madrid, Spain, 28222
      • Hospital Universitario Puerta de Hierro
• United Kingdom
  • Brighton, United Kingdom, BN2 5BD
    • Brighton and Sussex Univ Hosp
  • Manchester, United Kingdom, M20 4BX
    • Christie Hospital NHS Trust
  • Northwood, United Kingdom, HA6 2RN
    • Mount Vernon Hospital; Centre For Cancer Treatment
  • Nottingham, United Kingdom, NG5 1PB
    • Nottingham City Hospital; Oncology
  • Wirral, United Kingdom, CH63 4JY
    • The Clatterbridge Cancer Ctr For Oncolgy
• United States
  • California
    • Bakersfield, California, United States, 93309
      • Comprehensive Blood/Cancer Ctr
    • Fullerton, California, United States, 92835
      • St. Jude Heritage Healthcare; Virgiia K.Crosson Can Ctr
    • Los Angeles, California, United States, 90095-1772
      • Can Care Assoc Med Group Inc; Beach Cities Offices
    • Los Angeles, California, United States, 90095
      • Univ of California Los Angeles
    • Sacramento, California, United States, 95825
      • Kaiser Permanente Sacramento Medical Center
    • San Diego, California, United States, 92123
      • Sharp Healthcare; Oncology Research Program
    • Vallejo, California, United States, 94589
      • Kaiser Permanente - Vallejo
  • Florida
    • Fort Lauderdale, Florida, United States, 33308
      • Holy Cross Hospital
    • Fort Myers, Florida, United States, 33916
      • Florida Cancer Specialists; SCRI
  • Georgia
    • Lawrenceville, Georgia, United States, 30045
      • Suburban Hematology Oncology
  • Kansas
    • Wichita, Kansas, United States, 67214-3728
      • Cancer Center of Kansas
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Karmanos Cancer Institute..
  • Nevada
    • Las Vegas, Nevada, United States, 89128
      • Comprehensive Cancer Centers of Nevada
  • New York
    • East Setauket, New York, United States, 11733
      • North Shore Hem Onc Associates
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • Magee Womens Hospital
  • South Carolina
    • Charleston, South Carolina, United States, 29414
      • Charleston Hematology Oncology
    • Columbia, South Carolina, United States, 29210
      • South Carolina Onc. Associate
  • Tennessee
    • Chattanooga, Tennessee, United States, 37404
      • Scri Tennessee Oncology Chattanooga
    • Nashville, Tennessee, United States, 37203
      • The Sarah Cannon Research Inst
  • Texas
    • Houston, Texas, United States, 77030
      • MD Anderson Cancer Center
  • Utah
    • Ogden, Utah, United States, 84403
      • Northern Utah Associates

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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 Names: 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 Names: 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 Names: 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 Names: 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 Names: 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 Names: 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 Names: 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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

Outcome Measure	Time Frame
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)
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)
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)
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)
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)

Collaborators and Investigators

• Sponsor: Genentech, Inc.
• Collaborators: Hoffmann-La Roche

Publications and helpful links

General Publications

• Dieras 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.

Study record dates

Study Major Dates

• Study Start: March 1, 2011
• Primary Completion (Actual): March 1, 2016
• Study Completion (Actual): March 1, 2016

Study Registration Dates

• First Submitted: August 9, 2010
• First Submitted That Met QC Criteria: August 20, 2010
• First Posted (Estimate): August 23, 2010

Study Record Updates

• Last Update Posted (Estimate): January 20, 2017
• Last Update Submitted That Met QC Criteria: January 19, 2017
• Last Verified: January 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Triple Negative Breast Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Paclitaxel; Bevacizumab; Antibodies, Monoclonal
• Other Study ID Numbers: OAM4861g; GO01334 (Other Identifier: Hoffmann-La Roche); 2010-020101-32 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No