Clinical trial NCT01632228: A Study of Onartuzumab (MetMAb) in Combination With Bevacizumab Compared to Bevacizumab Alone or Onartuzumab Monotherapy in Participants With Recurrent Glioblastoma
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Glioblastoma
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2012-07-02
Enrollment: 135
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility 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

Primary outcomes:
measure: Progression-free survival (PFS) as Assessed by Investigator According to Response Assessment in Neuro-Oncology (RANO) Criteria
timeFrame: Baseline until disease progression, intolerable toxicity, participant or physician decision, or death, whichever occurs first (assessed every 6 weeks up to 18 months)
measure: Progression-free survival (PFS) as Assessed by Investigator According to RANO Criteria (in Participants With Met-Positive Glioblastoma)
timeFrame: 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:
measure: Overall Survival (All Participants)
timeFrame: Baseline until death (up to approximately 18 months)
measure: Percentage of Participants who Survived at Month 9 (All Participants)
timeFrame: Month 9
measure: Percentage of Participants who are Progression Free at Month 6, as Assessed by RANO Criteria (All Participants)
timeFrame: Month 6
measure: Percentage of Participants With Objective Response (OR), as Assessed by RANO Criteria (All Participants)
timeFrame: Baseline until disease progression, intolerable toxicity, participant or physician decision, or death, whichever occurs first (assessed every 6 weeks up to 18 months)
measure: Duration of Response, as Assessed by RANO Criteria
timeFrame: Baseline until disease progression, intolerable toxicity, participant or physician decision, or death, whichever occurs first (assessed every 6 weeks up to 18 months)
measure: Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: Baseline up to approximately 3 years 8 months
measure: Percentage of Participants With Serum Anti-Therapeutic Antibody (ATAs) to Onartuzumab
timeFrame: 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)
measure: Overall Survival (in Participants With Met-Positive Glioblastoma)
timeFrame: Baseline until death (up to approximately 18 months)
measure: Percentage of Participants who Survived at Month 9 (in Participants With Met-Positive Glioblastoma)
timeFrame: Month 9
measure: Percentage of Participants who are Progression Free at Month 6, as Assessed by RANO Criteria (in Participants With Met-Positive Glioblastoma)
timeFrame: Month 6
measure: Percentage of Participants With Objective Response (OR), as Assessed by RANO Criteria (in Participants With Met-Positive Glioblastoma)
timeFrame: Baseline until disease progression, intolerable toxicity, participant or physician decision, or death, whichever occurs first (assessed every 6 weeks up to 18 months)
measure: Duration of Response, as Assessed by RANO Criteria (in Participants With Met-Positive Glioblastoma)
timeFrame: Baseline until disease progression, intolerable toxicity, participant or physician decision, or death, whichever occurs first (assessed every 6 weeks up to 18 months)
measure: Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) in Participants With Met-Positive Glioblastoma
timeFrame: Baseline up to approximately 3 years 8 months
measure: Minimum Observed Serum Concentration (Cmin) of Onartuzumab
timeFrame: 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)
measure: Maximum Observed Serum Concentration (Cmax) of Onartuzumab
timeFrame: 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)
measure: Minimum Observed Serum Concentration (Cmin) of Bevacizumab
timeFrame: 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)
measure: Maximum Observed Serum Concentration (Cmax) of Bevacizumab
timeFrame: 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)
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama At Birmingham; Neuro-Oncology
state: Alabama
city: Los Angeles
country: United States
facility: Cedars Sinai Medical Center; Neurosurgery
state: California
city: Los Angeles
country: United States
facility: UCLA
state: California
city: San Francisco
country: United States
facility: USCF - Neurosurgery
state: California
city: Stanford
country: United States
facility: Stanford Comprehensive Cancer Center
state: California
city: Aurora
country: United States
facility: University of Colorado
state: Colorado
city: Englewood
country: United States
facility: Florida Cancer Specialists - Englewood
state: Florida
city: Saint Petersburg
country: United States
facility: Florida Cancer Specialists (St. Petersburg - St. Anthony's Professional Building)
state: Florida
city: Tampa
country: United States
facility: Moffitt Cancer Center
state: Florida
city: Chicago
country: United States
facility: North Western Univ; Neurology
state: Illinois
city: Evanston
country: United States
facility: Northshore University Health System; Cardiology
state: Illinois
city: Detroit
country: United States
facility: Henry Ford Health System
state: Michigan
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Cincinnati
country: United States
facility: Hatton Research Institutes
state: Ohio
city: Nashville
country: United States
facility: Sarah Cannon Cancer Center - Tennessee Oncology, Pllc
state: Tennessee
city: Dallas
country: United States
facility: Baylor Research Inst.
state: Texas
city: Charlottesville
country: United States
facility: University of Virgina
state: Virginia
city: Richmond
country: United States
facility: Virginia Cancer Institute
state: Virginia
city: Seattle
country: United States
facility: Seattle Cancer Care Alliance; Investigational Drug Service
state: Washington
city: Hamilton
country: Canada
facility: Hamilton Health Sciences - Juravinski Cancer Centre
state: Ontario
city: London
country: Canada
facility: London Health Sciences Centre
state: Ontario
city: Toronto
country: Canada
facility: Sunnybrook Health Science Centre
state: Ontario
city: Toronto
country: Canada
facility: Princess Margaret Hospital; Pencer Brain Tumour Centre, 18-727
state: Ontario
city: Montreal
country: Canada
facility: McGill University; Montreal Neurological Institute; Oncology
state: Quebec
city: Sherbrooke
country: Canada
facility: CHUS Hopital Fleurimont; CRC
state: Quebec
city: Bobigny
country: France
facility: Hopital Avicenne; Neurologie
city: Bron
country: France
facility: Hopital neurologique Pierre Wertheimer - CHU Lyon; Neurologie
city: Lille
country: France
facility: Hopital Roger Salengro
city: Marseille
country: France
facility: Hopital de La Timone - CHU de Marseille; Service de neuro-oncologie - Hôpital Adultes - 12ème étage
city: Montpellier
country: France
facility: Centre Val Aurelle Paul Lamarque; Medecine B3
city: Nancy
country: France
facility: Hôpital Central; Departement de Neuro-Oncologie
city: Paris
country: France
facility: Hopital Pitié Salpétrière - CHU; Service de neurologie 2 - Mazarin
city: Saint Herblain
country: France
facility: Ico Rene Gauducheau; Oncologie
city: Toulouse Cedex 9
country: France
facility: Hopital Purpan
city: Bonn
country: Germany
facility: Universitätsklinikum Bonn; Medizinische Klinik und Poliklinik I; Allgemeine Innere Medizin
city: Frankfurt am Main
country: Germany
facility: Klinikum Joh.Wolfg.Goethe-UNI Senckenbergisches Institut für Neuroonkologie
city: Hamburg
country: Germany
facility: Universitatsklinikum Hamburg-Eppendorf; Klinik und Poliklinik fur Neurochirurgie
city: Ibbenbühren
country: Germany
facility: Ärztehaus Velen
city: Köln
country: Germany
facility: Universitätsklinikum Köln
city: Mainz
country: Germany
facility: Klinikum der Johannes Gutenberg Uni Mainz; Studienz. Neurologie, Klinik und Poliklinik Neurologie
city: München
country: Germany
facility: Uni Klinikum München - Großhardern; Med. Klinik U. Poliklinik III - Abt. Onkologie u. Hämatologie
city: Oldenburg
country: Germany
facility: Pius-Hospital
city: Bologna
country: Italy
facility: Ospedale Bellaria; U.O. Oncologia Medica
state: Emilia-Romagna
city: Cesena
country: Italy
facility: Presidio Ospedaliero Marconi Bufalini; U.O. di Oncologia
state: Emilia-Romagna
city: Parma
country: Italy
facility: A.O. Universitaria Di Parma; Oncologia Medica
state: Emilia-Romagna
city: Brescia
country: Italy
facility: Spedali Civili di Brescia
state: Lombardia
city: Milano
country: Italy
facility: Fondazione IRCCS Ospedale Maggiore Policlinico; Gastroenterologia
state: Lombardia
city: Milano
country: Italy
facility: Fondazione IRCCS Istituto Neurologico C. Besta; Neuro-oncologia Sperimentale e Terapia Genica
state: Lombardia
city: Torino
country: Italy
facility: Azienda Ospedaliera Città della Salute e della Scienza di Torino
state: Piemonte
city: Pisa
country: Italy
facility: Az. Osp. Pisana Ospedale S. Chiara; U.O. Di Reumatologia
state: Toscana
city: Badalona
country: Spain
facility: Hospital Universitari Germans Trias i Pujol; Servicio de Oncologia
state: Barcelona
city: Pamplona
country: Spain
facility: Clinica Universitaria de Navarra; Servicio de Oncologia
state: Navarra
city: Barcelona
country: Spain
facility: Hospital Clinic i Provincial; Servicio de Farmacia
city: Barcelona
country: Spain
facility: Institut Catala d Oncologia Hospital Duran i Reynals
city: Madrid
country: Spain
facility: Hospital Ramon y Cajal; Servicio de Oncologia
city: Madrid
country: Spain
facility: HOSPITAL DE MADRID NORTE SANCHINARRO- CENTRO INTEGRAL ONCOLOGICO CLARA CAMPAL; Servicio de Oncologia
city: Malaga
country: Spain
facility: Hospital Regional Universitario Carlos Haya; Servicio de Oncologia
city: Geneve
country: Switzerland
facility: HUG; Oncologie
city: Zürich
country: Switzerland
facility: Universitätsspital Zürich; Klinik für Neurologie
city: Bristol
country: United Kingdom
facility: Bristol Haematology and Oncology Centre
city: London
country: United Kingdom
facility: Sarah Cannon Research Institute
city: Nottingham
country: United Kingdom
facility: Nottingham City Hospital; David Evans Centre
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: