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

Glioblastoma Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01632228
• Other study ID #: GO27819
• Secondary ID: 2011-005912-27
• Status: Completed
• Phase: Phase 2
• First received: June 28, 2012
• Last updated: February 2, 2018
• Start date: June 29, 2012
• Est. completion date: January 21, 2016

Study information

• Verified date: February 2018
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 135
• Est. completion date: January 21, 2016
• Est. primary completion date: January 21, 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Glioblastoma

Intervention

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

Locations

Country	Name	City	State
Canada	Hamilton Health Sciences - Juravinski Cancer Centre	Hamilton	Ontario
Canada	London Health Sciences Centre	London	Ontario
Canada	McGill University; Montreal Neurological Institute; Oncology	Montreal	Quebec
Canada	CHUS Hopital Fleurimont; CRC	Sherbrooke	Quebec
Canada	Princess Margaret Hospital; Pencer Brain Tumour Centre, 18-727	Toronto	Ontario
Canada	Sunnybrook Health Science Centre	Toronto	Ontario
France	Hopital Avicenne; Neurologie	Bobigny
France	Hopital neurologique Pierre Wertheimer - CHU Lyon; Neurologie	Bron
France	Hopital Roger Salengro	Lille
France	Hopital de La Timone - CHU de Marseille; Service de neuro-oncologie - Hôpital Adultes - 12ème étage	Marseille
France	Centre Val Aurelle Paul Lamarque; Medecine B3	Montpellier
France	Hôpital Central; Departement de Neuro-Oncologie	Nancy
France	Hopital Pitié Salpétrière - CHU; Service de neurologie 2 - Mazarin	Paris
France	Ico Rene Gauducheau; Oncologie	Saint Herblain
France	Hopital Purpan	Toulouse Cedex 9
Germany	Universitätsklinikum Bonn; Medizinische Klinik und Poliklinik I; Allgemeine Innere Medizin	Bonn
Germany	Klinikum Joh.Wolfg.Goethe-UNI Senckenbergisches Institut für Neuroonkologie	Frankfurt am Main
Germany	Universitatsklinikum Hamburg-Eppendorf; Klinik und Poliklinik fur Neurochirurgie	Hamburg
Germany	Ärztehaus Velen	Ibbenbühren
Germany	Universitätsklinikum Köln	Köln
Germany	Klinikum der Johannes Gutenberg Uni Mainz; Studienz. Neurologie, Klinik und Poliklinik Neurologie	Mainz
Germany	Uni Klinikum München - Großhardern; Med. Klinik U. Poliklinik III - Abt. Onkologie u. Hämatologie	München
Germany	Pius-Hospital	Oldenburg
Italy	Ospedale Bellaria; U.O. Oncologia Medica	Bologna	Emilia-Romagna
Italy	Spedali Civili di Brescia	Brescia	Lombardia
Italy	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	Fondazione IRCCS Ospedale Maggiore Policlinico; Gastroenterologia	Milano	Lombardia
Italy	A.O. Universitaria Di Parma; Oncologia Medica	Parma	Emilia-Romagna
Italy	Az. Osp. Pisana Ospedale S. Chiara; U.O. Di Reumatologia	Pisa	Toscana
Italy	Azienda Ospedaliera Città della Salute e della Scienza di Torino	Torino	Piemonte
Spain	Hospital Universitari Germans Trias i Pujol; Servicio de Oncologia	Badalona	Barcelona
Spain	Hospital Clinic i Provincial; Servicio de Farmacia	Barcelona
Spain	Institut Catala d Oncologia Hospital Duran i Reynals	Barcelona
Spain	HOSPITAL DE MADRID NORTE SANCHINARRO- CENTRO INTEGRAL ONCOLOGICO CLARA CAMPAL; Servicio de Oncologia	Madrid
Spain	Hospital Ramon y Cajal; Servicio de Oncologia	Madrid
Spain	Hospital Regional Universitario Carlos Haya; Servicio de Oncologia	Malaga
Spain	Clinica Universitaria de Navarra; Servicio de Oncologia	Pamplona	Navarra
Switzerland	HUG; Oncologie	Geneve
Switzerland	Universitätsspital Zürich; Klinik für Neurologie	Zürich
United Kingdom	Bristol Haematology and Oncology Centre	Bristol
United Kingdom	Sarah Cannon Research Institute	London
United Kingdom	Nottingham City Hospital; David Evans Centre	Nottingham
United States	University of Colorado	Aurora	Colorado
United States	University of Alabama At Birmingham; Neuro-Oncology	Birmingham	Alabama
United States	University of Virgina	Charlottesville	Virginia
United States	North Western Univ; Neurology	Chicago	Illinois
United States	Hatton Research Institutes	Cincinnati	Ohio
United States	Baylor Research Inst.	Dallas	Texas
United States	Henry Ford Health System	Detroit	Michigan
United States	Duke University Medical Center	Durham	North Carolina
United States	Florida Cancer Specialists - Englewood	Englewood	Florida
United States	Northshore University Health System; Cardiology	Evanston	Illinois
United States	Cedars Sinai Medical Center; Neurosurgery	Los Angeles	California
United States	UCLA	Los Angeles	California
United States	Sarah Cannon Cancer Center - Tennessee Oncology, Pllc	Nashville	Tennessee
United States	Virginia Cancer Institute	Richmond	Virginia
United States	Florida Cancer Specialists (St. Petersburg - St. Anthony's Professional Building)	Saint Petersburg	Florida
United States	USCF - Neurosurgery	San Francisco	California
United States	Seattle Cancer Care Alliance; Investigational Drug Service	Seattle	Washington
United States	Stanford Comprehensive Cancer Center	Stanford	California
United States	Moffitt Cancer Center	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

United States,  Canada,  France,  Germany,  Italy,  Spain,  Switzerland,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)
Primary	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	Overall Survival (All Participants)		Baseline until death (up to approximately 18 months)
Secondary	Percentage of Participants who Survived at Month 9 (All Participants)		Month 9
Secondary	Percentage of Participants who are Progression Free at Month 6, as Assessed by RANO Criteria (All Participants)		Month 6
Secondary	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)
Secondary	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)
Secondary	Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)		Baseline up to approximately 3 years 8 months
Secondary	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)
Secondary	Overall Survival (in Participants With Met-Positive Glioblastoma)		Baseline until death (up to approximately 18 months)
Secondary	Percentage of Participants who Survived at Month 9 (in Participants With Met-Positive Glioblastoma)		Month 9
Secondary	Percentage of Participants who are Progression Free at Month 6, as Assessed by RANO Criteria (in Participants With Met-Positive Glioblastoma)		Month 6
Secondary	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)
Secondary	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)
Secondary	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
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)