Clinical trial NCT01186991: 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: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Breast Cancer
Lead sponsor: Genentech, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Hoffmann-La Roche
First posted: 2010-08-23
Enrollment: 185
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).


Eligibility 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

Primary outcomes:
measure: 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
timeFrame: 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:
measure: PFS According to RECIST v1.1 in Participants Who Have not Received Prior Systemic Therapy
timeFrame: 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)
measure: Percentage of Participants With Objective Response as Assessed by the Investigator According to RECIST v1.1
timeFrame: 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)
measure: Duration of Response as Assessed by the Investigator Using RECIST v1.1
timeFrame: 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)
measure: Overall Survival (OS)
timeFrame: 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)
measure: Percentage of Participants With Adverse Events (AE) and Serious Adverse Events (SAEs)
timeFrame: 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)
measure: Number of Cycles of Treatment Received for Onartuzumab, Paclitaxel, and Bevacizumab During the Study
timeFrame: 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)
measure: Percentage of Participants With Anti-therapeutic Antibodies (ATAs) Against Onartuzumab
timeFrame: 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)
measure: Serum Levels of ATAs Against Onartuzumab
timeFrame: 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)
Other outcomes:
Locations:
city: Bakersfield
country: United States
facility: Comprehensive Blood/Cancer Ctr
state: California
city: Fullerton
country: United States
facility: St. Jude Heritage Healthcare; Virgiia K.Crosson Can Ctr
state: California
city: Los Angeles
country: United States
facility: Can Care Assoc Med Group Inc; Beach Cities Offices
state: California
city: Los Angeles
country: United States
facility: Univ of California Los Angeles
state: California
city: Sacramento
country: United States
facility: Kaiser Permanente Sacramento Medical Center
state: California
city: San Diego
country: United States
facility: Sharp Healthcare; Oncology Research Program
state: California
city: Vallejo
country: United States
facility: Kaiser Permanente - Vallejo
state: California
city: Fort Lauderdale
country: United States
facility: Holy Cross Hospital
state: Florida
city: Fort Myers
country: United States
facility: Florida Cancer Specialists; SCRI
state: Florida
city: Lawrenceville
country: United States
facility: Suburban Hematology Oncology
state: Georgia
city: Wichita
country: United States
facility: Cancer Center of Kansas
state: Kansas
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Detroit
country: United States
facility: Karmanos Cancer Institute..
state: Michigan
city: Las Vegas
country: United States
facility: Comprehensive Cancer Centers of Nevada
state: Nevada
city: East Setauket
country: United States
facility: North Shore Hem Onc Associates
state: New York
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Pittsburgh
country: United States
facility: Magee Womens Hospital
state: Pennsylvania
city: Charleston
country: United States
facility: Charleston Hematology Oncology
state: South Carolina
city: Columbia
country: United States
facility: South Carolina Onc. Associate
state: South Carolina
city: Chattanooga
country: United States
facility: SCRI Tennessee Oncology Chattanooga
state: Tennessee
city: Nashville
country: United States
facility: The Sarah Cannon Research Inst
state: Tennessee
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: Ogden
country: United States
facility: Northern Utah Associates
state: Utah
city: Bruxelles
country: Belgium
facility: Institut Jules Bordet
city: Edegem
country: Belgium
facility: UZ Antwerpen
city: Gent
country: Belgium
facility: AZ Sint Lucas (Sint Lucas)
city: Haine-Saint-Paul
country: Belgium
facility: CH Jolimont - Lobbes (Jolimont)
city: Hasselt
country: Belgium
facility: Jessa Zkh (Campus Virga Jesse)
city: Liège
country: Belgium
facility: CHU Sart-Tilman
city: Wilrijk
country: Belgium
facility: Sint Augustinus Wilrijk
city: Bordeaux
country: France
facility: Institut Bergonie; Oncologie
city: Caen
country: France
facility: Centre Francois Baclesse; Gastro-Enterologie
city: Dijon
country: France
facility: Centre Georges Francois Leclerc; Oncologie 3
city: Lyon
country: France
facility: Centre Leon Berard
city: Montpellier
country: France
facility: Institut régional du Cancer Montpellier
city: Paris
country: France
facility: Institut Curie; Oncologie Medicale
city: Saint Herblain
country: France
facility: Ico Rene Gauducheau; Oncologie
city: St Cloud
country: France
facility: Centre Rene Huguenin; CONSULT SPECIALISEES
city: Toulouse
country: France
facility: Institut Claudius Regaud; Departement Oncologie Medicale
city: Aschaffenburg
country: Germany
facility: Praxis Dr. med. Klausmann; SHOD
city: Frankfurt am Main
country: Germany
facility: Klinik Johann Wolfgang von Goethe Uni
city: Muenchen
country: Germany
facility: Klinikum rechts der Isar der TU München; Frauenklinik
city: Tübingen
country: Germany
facility: Universitätsklinik Tübingen; Frauenklinik
city: Cádiz
country: Spain
facility: Hospital Universitario Puerta del Mar; Servicio de Oncologia
state: Cadiz
city: Majadahonda
country: Spain
facility: Hospital Universitario Puerta de Hierro
state: Madrid
city: Barcelona
country: Spain
facility: Hospital Univ Vall d'Hebron; Servicio de Oncologia
city: Barcelona
country: Spain
facility: Instituto Catalán de Oncología; Servicio de Farmacia
city: La Coruña
country: Spain
facility: Centro Oncológico Gallego José Antonio Quiroga y Piñeiro, Servicio de Oncologia
city: Brighton
country: United Kingdom
facility: Brighton and Sussex Univ Hosp
city: Manchester
country: United Kingdom
facility: Christie Hospital NHS Trust
city: Northwood
country: United Kingdom
facility: Mount Vernon Hospital; Centre For Cancer Treatment
city: Nottingham
country: United Kingdom
facility: Nottingham City Hospital; Oncology
city: Wirral
country: United Kingdom
facility: The Clatterbridge Cancer Ctr For Oncolgy
Study officials:
affiliation: Genentech, Inc.
name: Clinical Trials
role: STUDY_DIRECTOR
References:
citation: 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.