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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT01632228
First received: June 28, 2012
Last updated: January 26, 2017
Last verified: January 2017
  Purpose
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.

Condition Intervention Phase
Glioblastoma Drug: Bevacizumab Drug: Onartuzumab Drug: Placebo Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Participant, Investigator
Primary Purpose: Treatment
Official Title: A Randomized, Double-Blind, Placebo-Controlled, Multicenter Phase II Study Evaluating the Efficacy and Safety of Onartuzumab in Combination With Bevacizumab or Onartuzumab Monotherapy in Patients With Recurrent Glioblastoma

Resource links provided by NLM:


Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:
  • Progression-free survival (PFS) as Assessed by Investigator According to Response Assessment in Neuro-Oncology (RANO) Criteria [ Time Frame: 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) [ Time Frame: 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:
  • Overall Survival (All Participants) [ Time Frame: Baseline until death (up to approximately 18 months) ]
  • Percentage of Participants who Survived at Month 9 (All Participants) [ Time Frame: Month 9 ]
  • Percentage of Participants who are Progression Free at Month 6, as Assessed by RANO Criteria (All Participants) [ Time Frame: Month 6 ]
  • Percentage of Participants With Objective Response (OR), as Assessed by RANO Criteria (All Participants) [ Time Frame: 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 [ Time Frame: 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) [ Time Frame: Baseline up to approximately 3 years 8 months ]
  • Percentage of Participants With Serum Anti-Therapeutic Antibody (ATAs) to Onartuzumab [ Time Frame: 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) ]
  • Overall Survival (in Participants With Met-Positive Glioblastoma) [ Time Frame: Baseline until death (up to approximately 18 months) ]
  • Percentage of Participants who Survived at Month 9 (in Participants With Met-Positive Glioblastoma) [ Time Frame: Month 9 ]
  • Percentage of Participants who are Progression Free at Month 6, as Assessed by RANO Criteria (in Participants With Met-Positive Glioblastoma) [ Time Frame: Month 6 ]
  • Percentage of Participants With Objective Response (OR), as Assessed by RANO Criteria (in Participants With Met-Positive Glioblastoma) [ Time Frame: 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) [ Time Frame: 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 [ Time Frame: Baseline up to approximately 3 years 8 months ]
  • Minimum Observed Serum Concentration (Cmin) of Onartuzumab [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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) ]

Enrollment: 135
Study Start Date: June 2012
Study Completion Date: January 2016
Primary Completion Date: January 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Onartuzumab + Bevacizumab
All participants will receive onartuzumab intravenous (IV) infusion followed by bevacizumab IV infusion every 3 weeks.
Drug: Bevacizumab
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.
Drug: Onartuzumab
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.
Other Name: MetMAb, RO5490258
Active Comparator: Placebo + Bevacizumab
All participants will receive placebo matched with onartuzumab followed by bevacizumab IV infusion every 3 weeks.
Drug: Bevacizumab
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.
Drug: Placebo
Participants will receive placebo matched with onartuzumab until disease progression, unacceptable toxicity, participants or physician decision to discontinue, or death.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01632228

  Hide Study Locations
Locations
United States, Alabama
University of Alabama At Birmingham; Neuro-Oncology
Birmingham, Alabama, United States, 35294
United States, California
Cedars Sinai Medical Center; Neurosurgery
Los Angeles, California, United States, 90048
UCLA
Los Angeles, California, United States, 90095
USCF - Neurosurgery
San Francisco, California, United States, 94143
Stanford Comprehensive Cancer Center
Stanford, California, United States, 94305
United States, Colorado
University of Colorado
Aurora, Colorado, United States, 80045
United States, Florida
Florida Cancer Specialists - Englewood
Englewood, Florida, United States, 34223
Florida Cancer Specialists (St. Petersburg - St. Anthony's Professional Building)
Saint Petersburg, Florida, United States, 33705
Moffitt Cancer Center
Tampa, Florida, United States, 33612
United States, Illinois
North Western Univ; Neurology
Chicago, Illinois, United States, 60611
Northshore University Health System; Cardiology
Evanston, Illinois, United States, 60201
United States, Michigan
Henry Ford Health System
Detroit, Michigan, United States, 48202
United States, North Carolina
Duke University Medical Center
Durham, North Carolina, United States, 27710
United States, Ohio
Hatton Research Institutes
Cincinnati, Ohio, United States, 45220
United States, Tennessee
Sarah Cannon Cancer Center - Tennessee Oncology, Pllc
Nashville, Tennessee, United States, 37203
United States, Texas
Baylor Research Inst.
Dallas, Texas, United States, 75246
United States, Virginia
University of Virgina
Charlottesville, Virginia, United States, 22908
Virginia Cancer Institute
Richmond, Virginia, United States, 23226
United States, Washington
Seattle Cancer Care Alliance; Investigational Drug Service
Seattle, Washington, United States, 98101
Canada, Ontario
Hamilton Health Sciences - Juravinski Cancer Centre
Hamilton, Ontario, Canada, L8V 5C2
London Health Sciences Centre
London, Ontario, Canada, N6A 4L6
Sunnybrook Health Science Centre
Toronto, Ontario, Canada, M4N 3M5
Princess Margaret Hospital; Pencer Brain Tumour Centre, 18-727
Toronto, Ontario, Canada, M5G 2M9
Canada, Quebec
McGill University; Montreal Neurological Institute; Oncology
Montreal, Quebec, Canada, H3A 2B4
CHUS Hopital Fleurimont; CRC
Sherbrooke, Quebec, Canada, J1H 5N4
France
Hopital Avicenne; Neurologie
Bobigny, France, 93009
Hopital neurologique Pierre Wertheimer - CHU Lyon; Neurologie
Bron, France, 69677
Hopital Roger Salengro
Lille, France, 59037
Hopital de La Timone - CHU de Marseille; Service de neuro-oncologie - Hôpital Adultes - 12ème étage
Marseille, France, 13385
Centre Val Aurelle Paul Lamarque; Medecine B3
Montpellier, France, 34298
Hôpital Central; Departement de Neuro-Oncologie
Nancy, France, 54000
Hopital Pitié Salpétrière - CHU; Service de neurologie 2 - Mazarin
Paris, France, 75651
Ico Rene Gauducheau; Oncologie
Saint Herblain, France, 44805
Hopital Purpan
Toulouse Cedex 9, France, 31059
Germany
Campus Virchow-Klinikum CharitéCentrum 15 Klinik f.Neurochirurgie
Berlin, Germany, 13353
Universitätsklinikum Bonn; Medizinische Klinik und Poliklinik I; Allgemeine Innere Medizin
Bonn, Germany, 53127
Klinikum Joh.Wolfg.Goethe-UNI Senckenbergisches Institut für Neuroonkologie
Frankfurt am Main, Germany, 60528
Universitatsklinikum Hamburg-Eppendorf; Klinik und Poliklinik fur Neurochirurgie
Hamburg, Germany, 20246
Ärztehaus Velen
Ibbenbühren, Germany, 49479
Universitätsklinikum Köln
Köln, Germany, 50937
Klinikum der Johannes Gutenberg Uni Mainz; Studienz. Neurologie, Klinik und Poliklinik Neurologie
Mainz, Germany, 55131
Uni Klinikum München - Großhardern; Med. Klinik U. Poliklinik III - Abt. Onkologie u. Hämatologie
München, Germany, 81377
Pius-Hospital
Oldenburg, Germany, 26121
Italy
Ospedale Bellaria; U.O. Oncologia Medica
Bologna, Emilia-Romagna, Italy, 40133
Presidio Ospedaliero Marconi Bufalini; U.O. di Oncologia
Cesena, Emilia-Romagna, Italy, 47023
A.O. Universitaria Di Parma; Oncologia Medica
Parma, Emilia-Romagna, Italy, 43100
Spedali Civili di Brescia
Brescia, Lombardia, Italy, 25123
Fondazione IRCCS Ospedale Maggiore Policlinico; Gastroenterologia
Milano, Lombardia, Italy, 20122
Fondazione IRCCS Istituto Neurologico C. Besta; Neuro-oncologia Sperimentale e Terapia Genica
Milano, Lombardia, Italy, 20133
Azienda Ospedaliera Città della Salute e della Scienza di Torino
Torino, Piemonte, Italy, 10126
Az. Osp. Pisana Ospedale S. Chiara; U.O. Di Reumatologia
Pisa, Toscana, Italy, 56100
Spain
Clinica Universitaria de Navarra; Servicio de Oncologia
Pamplona, Navarra, Spain, 31008
Hospital Clinic i Provincial
Barcelona, Spain, 08036
Institut Catala d Oncologia Hospital Duran i Reynals
Barcelona, Spain, 08908
Hospital Universitari Germans Trias i Pujol; Servicio de Oncologia
Barcelona, Spain, 08916
Hospital Ramon y Cajal; Servicio de Oncologia
Madrid, Spain, 28034
HOSPITAL DE MADRID NORTE SANCHINARRO- CENTRO INTEGRAL ONCOLOGICO CLARA CAMPAL; Servicio de Oncologia
Madrid, Spain, 28050
Hospital Regional Universitario Carlos Haya; Servicio de Oncologia
Malaga, Spain, 29010
Switzerland
HUG; Oncologie
Geneve, Switzerland, 1211
Universitätsspital Zürich; Klinik für Neurologie
Zürich, Switzerland, 8091
United Kingdom
Bristol Haematology and Oncology Centre
Bristol, United Kingdom, BS2 8ED
Sarah Cannon Research Institute
London, United Kingdom, W1G 6AD
Nottingham City Hospital; David Evans Centre
Nottingham, United Kingdom, NG5 1PB
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
Study Director: Clinical Trials Hoffmann-La Roche
  More Information

Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT01632228     History of Changes
Other Study ID Numbers: GO27819
2011-005912-27 ( EudraCT Number )
Study First Received: June 28, 2012
Last Updated: January 26, 2017

Additional relevant MeSH terms:
Glioblastoma
Astrocytoma
Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Bevacizumab
Antibodies, Monoclonal
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors
Antineoplastic Agents
Immunologic Factors

ClinicalTrials.gov processed this record on August 16, 2017