A Study of Onartuzumab (MetMAb) in Combination With Bevacizumab Compared to Bevacizumab Alone or Onartuzumab Monotherapy in Participants With Recurrent Glioblastoma

NCT01632228 | Completed Phase 2

• 2 other identifiers: GO278192011-005912-27
• Study Type: interventional
• Target: 135
• Locations: 8 countries
• Sites: 62

Brief Summary

This randomized, double-blind, placebo-controlled, multicenter phase II study will evaluate the safety and efficacy of onartuzumab in combination with bevacizumab as compared to bevacizumab alone in participants with recurrent glioblastoma. Participants will be randomized 1:1 to receive either placebo plus bevacizumab every 3 weeks, or onartuzumab plus bevacizumab. Study treatment will continue until disease progression, unacceptable toxicity, participants or physician decision to discontinue, or death.

Conditions

Glioblastoma

Outcome Measures

Primary Outcomes (2)

• Progression-free survival (PFS) as Assessed by Investigator According to Response Assessment in Neuro-Oncology (RANO) Criteria

  Baseline until disease progression, intolerable toxicity, participant or physician decision, or death, whichever occurs first (assessed every 6 weeks up to 18 months)

• Progression-free survival (PFS) as Assessed by Investigator According to RANO Criteria (in Participants With Met-Positive Glioblastoma)

  Baseline until disease progression, intolerable toxicity, participant or physician decision, or death, whichever occurs first (assessed every 6 weeks up to 18 months)

Secondary Outcomes (17)

• Overall Survival (All Participants)

  Baseline until death (up to approximately 18 months)

• Percentage of Participants who Survived at Month 9 (All Participants)

  Month 9

• Percentage of Participants who are Progression Free at Month 6, as Assessed by RANO Criteria (All Participants)

  Month 6

• Percentage of Participants With Objective Response (OR), as Assessed by RANO Criteria (All Participants)

  Baseline until disease progression, intolerable toxicity, participant or physician decision, or death, whichever occurs first (assessed every 6 weeks up to 18 months)

• Duration of Response, as Assessed by RANO Criteria

  Baseline until disease progression, intolerable toxicity, participant or physician decision, or death, whichever occurs first (assessed every 6 weeks up to 18 months)

Study Arms (2)

Onartuzumab + Bevacizumab

EXPERIMENTAL

All participants will receive onartuzumab intravenous (IV) infusion followed by bevacizumab IV infusion every 3 weeks.

Drug: Bevacizumab; Drug: Onartuzumab

Placebo + Bevacizumab

ACTIVE COMPARATOR

All participants will receive placebo matched with onartuzumab followed by bevacizumab IV infusion every 3 weeks.

Drug: Bevacizumab; Drug: Placebo

Interventions

Bevacizumab DRUG

Participants will receive bevacizumab 15 milligrams per kilogram (mg/kg) IV infusion every 3 weeks until disease progression, unacceptable toxicity, participants or physician decision to discontinue, or death.

Onartuzumab + Bevacizumab; Placebo + Bevacizumab

Onartuzumab DRUG

Participants will receive onartuzumab 15 mg/kg IV infusion every 3 weeks until disease progression, unacceptable toxicity, participants or physician decision to discontinue, or death.

Also known as: MetMAb, RO5490258

Onartuzumab + Bevacizumab

Placebo DRUG

Participants will receive placebo matched with onartuzumab until disease progression, unacceptable toxicity, participants or physician decision to discontinue, or death.

Placebo + Bevacizumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically confirmed glioblastoma at first recurrence after concurrent or adjuvant chemoradiotherapy
• Imaging confirmation of first tumor progression or regrowth as defined by RANO criteria
• Prior treatment with temozolomide
• No more than one prior line of chemotherapy
• No prior treatment with bevacizumab or other vascular endothelial growth factor (VEGF)- or VEGF-receptor-targeted agent
• No prior exposure to experimental treatment targeting either hepatocyte growth factor (HGF) or Met pathway
• No prior treatment with prolifeprospan 20 with carmustine wafer
• No prior intracerebral agent
• Recovery from the toxic effects of prior therapy
• No evidence of recent hemorrhage on baseline magnetic resonance imaging (MRI) of the brain
• No need for urgent palliative intervention for primary disease (e.g. impending herniation)
• Karnofsky performance status greater than or equal to (\>=) 70 percent (%)
• Stable or decreasing dose of corticosteroids within 5 days prior to randomization
• Prior therapy with gamma knife or other focal high-dose radiotherapy is allowed, but the participant must have subsequent histologic documentation of recurrence, unless the recurrence is a new lesion outside the irradiated field
• Participants who have undergone recent surgery for recurrent or progressive tumor are eligible provided that: surgery must have confirmed the recurrence, a minimum of 28 days must have elapsed from the day of surgery to randomization and for core or needle biopsy, a minimum of 7 days must have elapsed prior to randomization, and craniotomy or intracranial biopsy site must be adequately healed and free of drainage or cellulitis, and the underlying cranioplasty must appear intact at the time of randomization

You may not qualify if:

• Pregnant or lactating women
• Inadequate hematologic, renal or liver function
• History or presence of serious cardio-vascular disease
• New York Heart Association Grade II or greater congestive heart failure
• History of another malignancy in the previous 3 years, except for in situ cancer or basal or squamous cell skin cancer
• Inadequately controlled hypertension (defined as systolic blood pressure greater than \[\>\]150 millimeter of mercury (mmHg) and/or diastolic blood pressure \>100 mmHg while on antihypertensive medication)
• Prior history of hypertensive crisis or hypertensive encephalopathy
• Significant vascular disease (e.g., aortic aneurysm requiring surgical repair or recent peripheral arterial thrombosis) within 6 months prior to randomization
• Evidence of bleeding diathesis or coagulopathy (in the absence of therapeutic anticoagulation)
• Known hypersensitivity to any excipients of onartuzumab or bevacizumab

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (62)

University of Alabama At Birmingham; Neuro-Oncology

Birmingham, Alabama, 35294, United States

Location

Cedars Sinai Medical Center; Neurosurgery

Los Angeles, California, 90048, United States

Location

UCLA

Los Angeles, California, 90095, United States

Location

USCF - Neurosurgery

San Francisco, California, 94143, United States

Location

Stanford Comprehensive Cancer Center

Stanford, California, 94305, United States

Location

University of Colorado

Aurora, Colorado, 80045, United States

Location

Florida Cancer Specialists - Englewood

Englewood, Florida, 34223, United States

Location

Florida Cancer Specialists (St. Petersburg - St. Anthony's Professional Building)

St. Petersburg, Florida, 33705, United States

Location

Moffitt Cancer Center

Tampa, Florida, 33647, United States

Location

North Western Univ; Neurology

Chicago, Illinois, 60611, United States

Location

Northshore University Health System; Cardiology

Evanston, Illinois, 60201, United States

Location

Henry Ford Health System

Detroit, Michigan, 48202, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Hatton Research Institutes

Cincinnati, Ohio, 45220, United States

Location

Sarah Cannon Cancer Center - Tennessee Oncology, Pllc

Nashville, Tennessee, 37203, United States

Location

Baylor Research Inst.

Dallas, Texas, 75246, United States

Location

University of Virgina

Charlottesville, Virginia, 22908, United States

Location

Virginia Cancer Institute

Richmond, Virginia, 23226, United States

Location

Seattle Cancer Care Alliance; Investigational Drug Service

Seattle, Washington, 98101, United States

Location

Hamilton Health Sciences - Juravinski Cancer Centre

Hamilton, Ontario, L8V 5C2, Canada

Location

London Health Sciences Centre

London, Ontario, N6A 4L6, Canada

Location

Sunnybrook Health Science Centre

Toronto, Ontario, M4N 3M5, Canada

Location

Princess Margaret Hospital; Pencer Brain Tumour Centre, 18-727

Toronto, Ontario, M5G 2M9, Canada

Location

McGill University; Montreal Neurological Institute; Oncology

Montreal, Quebec, H3A 2B4, Canada

Location

CHUS Hopital Fleurimont; CRC

Sherbrooke, Quebec, J1H 5N4, Canada

Location

Hopital Avicenne; Neurologie

Bobigny, 93009, France

Location

Hopital neurologique Pierre Wertheimer - CHU Lyon; Neurologie

Bron, 69677, France

Location

Hopital Roger Salengro

Lille, 59037, France

Location

Hopital de La Timone - CHU de Marseille; Service de neuro-oncologie - Hôpital Adultes - 12ème étage

Marseille, 13385, France

Location

Centre Val Aurelle Paul Lamarque; Medecine B3

Montpellier, 34298, France

Location

Hôpital Central; Departement de Neuro-Oncologie

Nancy, 54000, France

Location

Hopital Pitié Salpétrière - CHU; Service de neurologie 2 - Mazarin

Paris, 75651, France

Location

Ico Rene Gauducheau; Oncologie

Saint-Herblain, 44805, France

Location

Hopital Purpan

Toulouse, 31059, France

Location

Universitätsklinikum Bonn; Medizinische Klinik und Poliklinik I; Allgemeine Innere Medizin

Bonn, 53127, Germany

Location

Universitätsklinikum Köln

Cologne, 50937, Germany

Location

Klinikum Joh.Wolfg.Goethe-UNI Senckenbergisches Institut für Neuroonkologie

Frankfurt am Main, 60528, Germany

Location

Universitatsklinikum Hamburg-Eppendorf; Klinik und Poliklinik fur Neurochirurgie

Hamburg, 20246, Germany

Location

Ärztehaus Velen

Ibbenbühren, 49479, Germany

Location

Klinikum der Johannes Gutenberg Uni Mainz; Studienz. Neurologie, Klinik und Poliklinik Neurologie

Mainz, 55131, Germany

Location

Uni Klinikum München - Großhardern; Med. Klinik U. Poliklinik III - Abt. Onkologie u. Hämatologie

München, 81377, Germany

Location

Pius-Hospital

Oldenburg, 26121, Germany

Location

Ospedale Bellaria; U.O. Oncologia Medica

Bologna, Emilia-Romagna, 40133, Italy

Location

Presidio Ospedaliero Marconi Bufalini; U.O. di Oncologia

Cesena, Emilia-Romagna, 47023, Italy

Location

A.O. Universitaria Di Parma; Oncologia Medica

Parma, Emilia-Romagna, 43100, Italy

Location

Spedali Civili di Brescia

Brescia, Lombardy, 25123, Italy

Location

Fondazione IRCCS Ospedale Maggiore Policlinico; Gastroenterologia

Milan, Lombardy, 20122, Italy

Location

Fondazione IRCCS Istituto Neurologico C. Besta; Neuro-oncologia Sperimentale e Terapia Genica

Milan, Lombardy, 20133, Italy

Location

Azienda Ospedaliera Città della Salute e della Scienza di Torino

Turin, Piedmont, 10126, Italy

Location

Az. Osp. Pisana Ospedale S. Chiara; U.O. Di Reumatologia

Pisa, Tuscany, 56100, Italy

Location

Hospital Universitari Germans Trias i Pujol; Servicio de Oncologia

Badalona, Barcelona, 08916, Spain

Location

Clinica Universitaria de Navarra; Servicio de Oncologia

Pamplona, Navarre, 31008, Spain

Location

Hospital Clinic i Provincial; Servicio de Farmacia

Barcelona, 08036, Spain

Location

Institut Catala d Oncologia Hospital Duran i Reynals

Barcelona, 08908, Spain

Location

Hospital Ramon y Cajal; Servicio de Oncologia

Madrid, 28034, Spain

Location

HOSPITAL DE MADRID NORTE SANCHINARRO- CENTRO INTEGRAL ONCOLOGICO CLARA CAMPAL; Servicio de Oncologia

Madrid, 28050, Spain

Location

Hospital Regional Universitario Carlos Haya; Servicio de Oncologia

Málaga, 29010, Spain

Location

HUG; Oncologie

Geneva, 1211, Switzerland

Location

Universitätsspital Zürich; Klinik für Neurologie

Zurich, 8091, Switzerland

Location

Bristol Haematology and Oncology Centre

Bristol, BS2 8ED, United Kingdom

Location

Sarah Cannon Research Institute

London, W1G 6AD, United Kingdom

Location

Nottingham City Hospital; David Evans Centre

Nottingham, NG5 1PB, United Kingdom

Location

MeSH Terms

Conditions

Glioblastoma

Interventions

Bevacizumab; onartuzumab

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 28, 2012
• First Posted: July 2, 2012
• Study Start: June 29, 2012
• Primary Completion: January 21, 2016
• Study Completion: January 21, 2016
• Last Updated: February 5, 2018

Record last verified: 2018-02

Locations

IT (8); CH (2); ES (7); GB (3); US (19); FR (9); CA (6); DE (8)