A Study of Onartuzumab (MetMAb) in Combination With Bevacizumab Compared to Bevacizumab Alone or Onartuzumab Monotherapy in Participants With Recurrent Glioblastoma
- Registration Number
- NCT01632228
- Lead Sponsor
- Hoffmann-La Roche
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 135
- 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
- Availability of formalin fixed paraffin embedded tumor tissue representative of glioblastoma
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Onartuzumab + Bevacizumab Onartuzumab All participants will receive onartuzumab intravenous (IV) infusion followed by bevacizumab IV infusion every 3 weeks. Placebo + Bevacizumab Placebo All participants will receive placebo matched with onartuzumab followed by bevacizumab IV infusion every 3 weeks. Onartuzumab + Bevacizumab Bevacizumab All participants will receive onartuzumab intravenous (IV) infusion followed by bevacizumab IV infusion every 3 weeks. Placebo + Bevacizumab Bevacizumab All participants will receive placebo matched with onartuzumab followed by bevacizumab IV infusion every 3 weeks.
- Primary Outcome Measures
Name Time Method 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 Outcome Measures
Name Time Method Overall Survival (in Participants With Met-Positive Glioblastoma) Baseline until death (up to approximately 18 months) Percentage of Participants who Survived at Month 9 (in Participants With Met-Positive Glioblastoma) Month 9 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) Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) Baseline up to approximately 3 years 8 months Percentage of Participants With Serum Anti-Therapeutic Antibody (ATAs) to Onartuzumab Predose (0 hour) on Day 1 of Cycles 1, 2, 3, 4, at study completion or study drug discontinuation visit (up to approximately 3.5 years; Cycle length: 21 days) Percentage of Participants who are Progression Free at Month 6, as Assessed by RANO Criteria (in Participants With Met-Positive Glioblastoma) Month 6 Percentage of Participants With Objective Response (OR), as Assessed by 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) Duration of Response, as Assessed by 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) Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) in Participants With Met-Positive Glioblastoma Baseline up to approximately 3 years 8 months Minimum Observed Serum Concentration (Cmin) of Onartuzumab predose (0 hour) on Day 1 of Cycles 1, 2, 3, 4, at study completion or study drug discontinuation visit (up to approximately 3.5 years) (Cycle length: 21 days; infusion duration: Onartuzumab 60 minutes) Maximum Observed Serum Concentration (Cmax) of Onartuzumab predose (0 hour) and 30 minutes post dose on Day 1 of Cycles 1, 2, 3, 4, at study completion or study drug discontinuation visit (up to approximately 3.5 years) (Cycle length: 21 days; infusion duration: Onartuzumab 60 minutes) Minimum Observed Serum Concentration (Cmin) of Bevacizumab predose (0 hour) on Day 1 of Cycles 1, 2, 3, 4, at study completion or study drug discontinuation visit (up to approximately 3.5 years) (Cycle length: 21 days; infusion duration: Bevacizumab 90 minutes) Maximum Observed Serum Concentration (Cmax) of Bevacizumab predose (0 hour) and 30 minutes post dose on Day 1 of Cycles 1, 2, 3, 4, at study completion or study drug discontinuation visit (up to approximately 3.5 years) (Cycle length: 21 days; infusion duration: Bevacizumab 90 minutes)
Trial Locations
- Locations (62)
Ärztehaus Velen
🇩🇪Ibbenbühren, Germany
McGill University; Montreal Neurological Institute; Oncology
🇨🇦Montreal, Quebec, Canada
London Health Sciences Centre
🇨🇦London, Ontario, Canada
Hôpital Central; Departement de Neuro-Oncologie
🇫🇷Nancy, France
Uni Klinikum München - Großhardern; Med. Klinik U. Poliklinik III - Abt. Onkologie u. Hämatologie
🇩🇪München, Germany
HUG; Oncologie
🇨ðŸ‡Geneve, Switzerland
Spedali Civili di Brescia
🇮🇹Brescia, Lombardia, Italy
Nottingham City Hospital; David Evans Centre
🇬🇧Nottingham, United Kingdom
Hopital Avicenne; Neurologie
🇫🇷Bobigny, France
Pius-Hospital
🇩🇪Oldenburg, Germany
Hospital Regional Universitario Carlos Haya; Servicio de Oncologia
🇪🇸Malaga, Spain
Hopital Roger Salengro
🇫🇷Lille, France
Florida Cancer Specialists (St. Petersburg - St. Anthony's Professional Building)
🇺🇸Saint Petersburg, Florida, United States
Bristol Haematology and Oncology Centre
🇬🇧Bristol, United Kingdom
Hopital neurologique Pierre Wertheimer - CHU Lyon; Neurologie
🇫🇷Bron, France
Hospital Ramon y Cajal; Servicio de Oncologia
🇪🇸Madrid, Spain
Hamilton Health Sciences - Juravinski Cancer Centre
🇨🇦Hamilton, Ontario, Canada
Hopital Pitié Salpétrière - CHU; Service de neurologie 2 - Mazarin
🇫🇷Paris, France
HOSPITAL DE MADRID NORTE SANCHINARRO- CENTRO INTEGRAL ONCOLOGICO CLARA CAMPAL; Servicio de Oncologia
🇪🇸Madrid, Spain
Centre Val Aurelle Paul Lamarque; Medecine B3
🇫🇷Montpellier, France
Hopital Purpan
🇫🇷Toulouse Cedex 9, France
Az. Osp. Pisana Ospedale S. Chiara; U.O. Di Reumatologia
🇮🇹Pisa, Toscana, Italy
Hospital Clinic i Provincial; Servicio de Farmacia
🇪🇸Barcelona, Spain
University of Virgina
🇺🇸Charlottesville, Virginia, United States
Universitätsklinikum Bonn; Medizinische Klinik und Poliklinik I; Allgemeine Innere Medizin
🇩🇪Bonn, Germany
Universitätsklinikum Köln
🇩🇪Köln, Germany
Fondazione IRCCS Ospedale Maggiore Policlinico; Gastroenterologia
🇮🇹Milano, Lombardia, Italy
Hopital de La Timone - CHU de Marseille; Service de neuro-oncologie - Hôpital Adultes - 12ème étage
🇫🇷Marseille, France
Universitatsklinikum Hamburg-Eppendorf; Klinik und Poliklinik fur Neurochirurgie
🇩🇪Hamburg, Germany
Stanford Comprehensive Cancer Center
🇺🇸Stanford, California, United States
Florida Cancer Specialists - Englewood
🇺🇸Englewood, Florida, United States
Ico Rene Gauducheau; Oncologie
🇫🇷Saint Herblain, France
Klinikum Joh.Wolfg.Goethe-UNI Senckenbergisches Institut für Neuroonkologie
🇩🇪Frankfurt am Main, Germany
Klinikum der Johannes Gutenberg Uni Mainz; Studienz. Neurologie, Klinik und Poliklinik Neurologie
🇩🇪Mainz, Germany
Presidio Ospedaliero Marconi Bufalini; U.O. di Oncologia
🇮🇹Cesena, Emilia-Romagna, Italy
Fondazione IRCCS Istituto Neurologico C. Besta; Neuro-oncologia Sperimentale e Terapia Genica
🇮🇹Milano, Lombardia, Italy
Azienda Ospedaliera Città della Salute e della Scienza di Torino
🇮🇹Torino, Piemonte, Italy
Hospital Universitari Germans Trias i Pujol; Servicio de Oncologia
🇪🇸Badalona, Barcelona, Spain
Universitätsspital Zürich; Klinik für Neurologie
🇨ðŸ‡Zürich, Switzerland
Clinica Universitaria de Navarra; Servicio de Oncologia
🇪🇸Pamplona, Navarra, Spain
University of Alabama At Birmingham; Neuro-Oncology
🇺🇸Birmingham, Alabama, United States
Cedars Sinai Medical Center; Neurosurgery
🇺🇸Los Angeles, California, United States
UCLA
🇺🇸Los Angeles, California, United States
USCF - Neurosurgery
🇺🇸San Francisco, California, United States
Duke University Medical Center
🇺🇸Durham, North Carolina, United States
Moffitt Cancer Center
🇺🇸Tampa, Florida, United States
Hatton Research Institutes
🇺🇸Cincinnati, Ohio, United States
Baylor Research Inst.
🇺🇸Dallas, Texas, United States
Princess Margaret Hospital; Pencer Brain Tumour Centre, 18-727
🇨🇦Toronto, Ontario, Canada
University of Colorado
🇺🇸Aurora, Colorado, United States
North Western Univ; Neurology
🇺🇸Chicago, Illinois, United States
Northshore University Health System; Cardiology
🇺🇸Evanston, Illinois, United States
Henry Ford Health System
🇺🇸Detroit, Michigan, United States
Virginia Cancer Institute
🇺🇸Richmond, Virginia, United States
Seattle Cancer Care Alliance; Investigational Drug Service
🇺🇸Seattle, Washington, United States
Sarah Cannon Cancer Center - Tennessee Oncology, Pllc
🇺🇸Nashville, Tennessee, United States
Sunnybrook Health Science Centre
🇨🇦Toronto, Ontario, Canada
CHUS Hopital Fleurimont; CRC
🇨🇦Sherbrooke, Quebec, Canada
Ospedale Bellaria; U.O. Oncologia Medica
🇮🇹Bologna, Emilia-Romagna, Italy
A.O. Universitaria Di Parma; Oncologia Medica
🇮🇹Parma, Emilia-Romagna, Italy
Institut Catala d Oncologia Hospital Duran i Reynals
🇪🇸Barcelona, Spain
Sarah Cannon Research Institute
🇬🇧London, United Kingdom