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

Breast Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01186991
• Other study ID #: OAM4861g
• Secondary ID: GO013342010-0201
• Status: Completed
• Phase: Phase 2
• First received: August 9, 2010
• Last updated: January 19, 2017
• Start date: March 2011
• Est. completion date: March 2016

Study information

• Verified date: January 2017
• Source: Genentech, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 185
• Est. completion date: March 2016
• Est. primary completion date: March 2016
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms
• Triple Negative Breast Neoplasms

Intervention

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.
• 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.
• 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.
• Bevacizumab Placebo
Placebo matching to bevacizumab will be administered as IV infusion on Day 1 and Day 15 of each 28-day cycle.
• Onartuzumab Placebo
Placebo matching to onartuzumab will be administered as IV infusion on Day 1 and Day 15 of each 28-day cycle.

Locations

Country	Name	City	State
Belgium	Institut Jules Bordet	Bruxelles
Belgium	UZ Antwerpen	Edegem
Belgium	AZ Sint Lucas (Sint Lucas)	Gent
Belgium	CH Jolimont - Lobbes (Jolimont)	Haine-Saint-Paul
Belgium	Jessa Zkh (Campus Virga Jesse)	Hasselt
Belgium	CHU Sart-Tilman	Liège
Belgium	Sint Augustinus Wilrijk	Wilrijk
France	Institut Bergonie; Oncologie	Bordeaux
France	Centre Francois Baclesse; Gastro-Enterologie	Caen
France	Centre Georges Francois Leclerc; Oncologie 3	Dijon
France	Centre Leon Berard	Lyon
France	Institut régional du Cancer Montpellier	Montpellier
France	Institut Curie; Oncologie Medicale	Paris
France	Ico Rene Gauducheau; Oncologie	Saint Herblain
France	Centre Rene Huguenin; CONSULT SPECIALISEES	St Cloud
France	Institut Claudius Regaud; Departement Oncologie Medicale	Toulouse
Germany	Praxis Dr. med. Klausmann; SHOD	Aschaffenburg
Germany	Klinik Johann Wolfgang von Goethe Uni	Frankfurt am Main
Germany	Klinikum rechts der Isar der TU München; Frauenklinik	Muenchen
Germany	Universitätsklinik Tübingen; Frauenklinik	Tübingen
Spain	Hospital Univ Vall d'Hebron; Servicio de Oncologia	Barcelona
Spain	Instituto Catalán de Oncología; Servicio de Farmacia	Barcelona
Spain	Hospital Universitario Puerta del Mar; Servicio de Oncologia	Cádiz	Cadiz
Spain	Centro Oncológico Gallego José Antonio Quiroga y Piñeiro, Servicio de Oncologia	La Coruña
Spain	Hospital Universitario Puerta de Hierro	Majadahonda	Madrid
United Kingdom	Brighton and Sussex Univ Hosp	Brighton
United Kingdom	Christie Hospital NHS Trust	Manchester
United Kingdom	Mount Vernon Hospital; Centre For Cancer Treatment	Northwood
United Kingdom	Nottingham City Hospital; Oncology	Nottingham
United Kingdom	The Clatterbridge Cancer Ctr For Oncolgy	Wirral
United States	Comprehensive Blood/Cancer Ctr	Bakersfield	California
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Charleston Hematology Oncology	Charleston	South Carolina
United States	SCRI Tennessee Oncology Chattanooga	Chattanooga	Tennessee
United States	South Carolina Onc. Associate	Columbia	South Carolina
United States	Karmanos Cancer Institute..	Detroit	Michigan
United States	Duke University Medical Center	Durham	North Carolina
United States	North Shore Hem Onc Associates	East Setauket	New York
United States	Holy Cross Hospital	Fort Lauderdale	Florida
United States	Florida Cancer Specialists; SCRI	Fort Myers	Florida
United States	St. Jude Heritage Healthcare; Virgiia K.Crosson Can Ctr	Fullerton	California
United States	MD Anderson Cancer Center	Houston	Texas
United States	Comprehensive Cancer Centers of Nevada	Las Vegas	Nevada
United States	Suburban Hematology Oncology	Lawrenceville	Georgia
United States	Can Care Assoc Med Group Inc; Beach Cities Offices	Los Angeles	California
United States	Univ of California Los Angeles	Los Angeles	California
United States	The Sarah Cannon Research Inst	Nashville	Tennessee
United States	Northern Utah Associates	Ogden	Utah
United States	Magee Womens Hospital	Pittsburgh	Pennsylvania
United States	Kaiser Permanente Sacramento Medical Center	Sacramento	California
United States	Sharp Healthcare; Oncology Research Program	San Diego	California
United States	Kaiser Permanente - Vallejo	Vallejo	California
United States	Cancer Center of Kansas	Wichita	Kansas

Sponsors (2)

Lead Sponsor	Collaborator
Genentech, Inc.	Hoffmann-La Roche

Countries where clinical trial is conducted

United States,  Belgium,  France,  Germany,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)