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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:
ClinicalTrials.gov Identifier:
NCT01632228
First Posted: July 2, 2012
Last Update Posted: January 27, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
Hoffmann-La Roche
June 28, 2012
July 2, 2012
January 27, 2017
June 2012
January 2016   (Final data collection date for primary outcome measure)
  • 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) ]
  • Progression-free survival (investigator-assessed): onartuzumab + bevacizumab versus placebo + bevacizumab [ Time Frame: 21 months ]
  • Progression-free survival (investigator-assessed) in subgroup with Met-positive glioblastoma: onartuzumab + bevacizumab versus placebo + bevacizumab [ Time Frame: 21 months ]
Complete list of historical versions of study NCT01632228 on ClinicalTrials.gov Archive Site
  • 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) ]
  • Overall survival in all patients [ Time Frame: 21 months ]
  • Overall survival rate at 9 months (OS-9) in all patients [ Time Frame: 21 months ]
  • Progression-free survival at 6 months (PFS-6) in all patients [ Time Frame: 21 months ]
  • Objective response rate in all patients according to Response Assessment in Neuro-Oncology (RANO) criteria [ Time Frame: 21 months ]
  • Duration of response in all patients [ Time Frame: 21 months ]
  • Safety: Incidence of adverse events in all patients [ Time Frame: 21 months ]
  • Immunogenicity: anti-therapeutic antibodies (ATAs) levels [ Time Frame: 21 months ]
  • Overall survival in Met-positive glioblastoma patients [ Time Frame: 21 months ]
  • Overall survival rate at 9 months (OS-9) in Met-positive glioblastoma patients [ Time Frame: 21 months ]
  • Progression-free survival at 6 months (PFS-6) in patients with Met positive tumors [ Time Frame: 21 months ]
  • Objective response rate in patients with Met-positive tumors according to Response Assessment in Neuro-Oncology (RANO) criteria [ Time Frame: 21 months ]
  • Duration of response in patients with Met-positive tumors [ Time Frame: 21 months ]
  • Safety: Incidence of adverse events in patients with Met-positive tumors [ Time Frame: 21 months ]
  • Immunogenicity: anti-therapeutic antibodies (ATAs) levels [ Time Frame: Pre-dose and 30 min post-dose Day 1, Cycles 1-4 ]
  • Pharmacokinetics: Cmin/Cmax [ Time Frame: Pre-dose and 30 min post-dose Day 1, Cycles 1-4 ]
Not Provided
Not Provided
 
A Study of Onartuzumab (MetMAb) in Combination With Bevacizumab Compared to Bevacizumab Alone or Onartuzumab Monotherapy in Participants With Recurrent Glioblastoma
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
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.
Not Provided
Interventional
Phase 2
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Glioblastoma
  • 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
  • Drug: Placebo
    Participants will receive placebo matched with onartuzumab until disease progression, unacceptable toxicity, participants or physician decision to discontinue, or death.
  • Experimental: Onartuzumab + Bevacizumab
    All participants will receive onartuzumab intravenous (IV) infusion followed by bevacizumab IV infusion every 3 weeks.
    Interventions:
    • Drug: Bevacizumab
    • Drug: Onartuzumab
  • Active Comparator: Placebo + Bevacizumab
    All participants will receive placebo matched with onartuzumab followed by bevacizumab IV infusion every 3 weeks.
    Interventions:
    • Drug: Bevacizumab
    • Drug: Placebo
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
135
January 2016
January 2016   (Final data collection date for primary outcome measure)

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
Sexes Eligible for Study: All
18 Years and older   (Adult, Senior)
No
Contact information is only displayed when the study is recruiting subjects
Canada,   France,   Germany,   Italy,   Spain,   Switzerland,   United Kingdom,   United States
 
 
NCT01632228
GO27819
2011-005912-27 ( EudraCT Number )
Not Provided
Not Provided
Not Provided
Hoffmann-La Roche
Hoffmann-La Roche
Not Provided
Study Director: Clinical Trials Hoffmann-La Roche
Hoffmann-La Roche
January 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP