A Study of Onartuzumab (MetMAb) in Combination With Bevacizumab Compared to Bevacizumab Alone or Onartuzumab Monotherapy in Participants With Recurrent Glioblastoma
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ClinicalTrials.gov Identifier: NCT01632228 |
Recruitment Status
:
Completed
First Posted
: July 2, 2012
Last Update Posted
: February 5, 2018
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Condition or disease | Intervention/treatment | Phase |
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Glioblastoma | Drug: Bevacizumab Drug: Onartuzumab Drug: Placebo | Phase 2 |
Study Type : | Interventional (Clinical Trial) |
Actual Enrollment : | 135 participants |
Allocation: | Randomized |
Intervention Model: | Parallel Assignment |
Masking: | Double (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 |
Actual Study Start Date : | June 29, 2012 |
Actual Primary Completion Date : | January 21, 2016 |
Actual Study Completion Date : | January 21, 2016 |

Arm | Intervention/treatment |
---|---|
Experimental: Onartuzumab + Bevacizumab
All participants will receive onartuzumab intravenous (IV) infusion followed by bevacizumab IV infusion every 3 weeks.
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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
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Active Comparator: Placebo + Bevacizumab
All participants will receive placebo matched with onartuzumab followed by bevacizumab IV infusion every 3 weeks.
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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.
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- 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) ]
- 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) ]

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

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01632228

Study Director: | Clinical Trials | Hoffmann-La Roche |
Responsible Party: | Hoffmann-La Roche |
ClinicalTrials.gov Identifier: | NCT01632228 History of Changes |
Other Study ID Numbers: |
GO27819 2011-005912-27 ( EudraCT Number ) |
First Posted: | July 2, 2012 Key Record Dates |
Last Update Posted: | February 5, 2018 |
Last Verified: | February 2018 |
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 |