Glioblastoma Multiforme
Conditions
Brief summary
This open-label, multicenter study will evaluate the safety and efficacy of RO5323441 in combination with Avastin (bevacizumab) in patients with recurrent glioblastoma. In the dose-finding part, patients will receive intravenous escalating doses of RO5323441 in combination with 10 mg/kg Avastin once every two weeks. In the efficacy-finding part, patients will be randomized to receive the established dose (from the dose-finding part) of RO5323441 plus Avastin or Avastin alone. Patients in the dose-finding part may continue treatment with RO5323441 and Avastin on the study until evidence of progressive disease or unacceptable adverse events happen. In the efficacy-finding part, patients will receive study treatment until disease progression or death.
Interventions
DRUGRO5323441 + bevacizumab [Avastin]
Dose-Finding part: RO5323441 intravenous escalating doses once every two weeks; Efficacy-Finding part: established dose from the Dose-Finding part; Avastin: 10 mg/kg intravenously once every two weeks
DRUGbevacizumab [Avastin]
Efficacy-Finding part: 10 mg/kg intravenously once every two weeks
Sponsors
Hoffmann-La Roche
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Adult patients, \>/=18 years of age * Histologically confirmed glioblastoma * Radiographic demonstration of disease progression by Response Assessment in Neurooncology (RANO) criteria following prior therapy * Availability of at least 1 formalin-fixed paraffin-embedded tumor tissue sample * If receiving corticosteroids, patients must have been on a stable or decreasing dose of corticosteroids * Prior standard radiotherapy for glioblastoma * Karnofsky Performance status \>/=70 * Over 4 weeks since prior surgical resection * Over 12 weeks from radiotherapy * Over 4 weeks from anticancer agents
Exclusion criteria
* Patients had second or later glioblastoma relapse * Patients received more than one systemic treatment regimen for glioblastoma * Patients have secondary glioblastoma * Prior treatment with Avastin * Patients unable to undergo Magnetic Resonance Imaging (MRI)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Dose-Finding Part: Dose limiting toxicity | Day 28 |
| Efficacy-Finding part: Progression-free survival | From baseline to disease progression or death (>12 months) |
Secondary
| Measure | Time frame |
|---|---|
| Dose-Finding part: Efficacy (tumor response according to Response Assessment in Neurooncology (RANO) criteria | From baseline to disease progression or death (>12 months) |
| Dose-Finding part: Glioblastoma biomarker | From baseline to disease progression or death (>12 months) |
| Efficacy-Finding part: Overall Response Rate | From baseline to disease progression or death (>12 months) |
| Efficacy-Finding part: Disease Control Rate | From baseline to disease progression or death (>12 months) |
| Efficacy-Finding part: Duration of Response | From baseline to disease progression or death (>12 months) |
| Dose-Finding part: Pharmacokinetics of RO5323441 and Avastin when combined | From baseline to disease progression or death (>12 months) |
| Efficacy-Finding part: Overall Survival | From baseline to disease progression or death (>12 months) |
| Efficacy-Finding part: Safety (incidence of adverse events) | From baseline to disease progression or death (>12 months) |
| Efficacy-Finding part: Glioblastoma biomarker | From baseline to disease progression or death (>12 months) |
| Efficacy-Finding part: Pharmacokinetics (serum levels) of RO5323441 and Avastin when combined | From baseline to disease progression or death (>12 months) |
| Efficacy-Finding part: Progression-free survival | From baseline to disease progression or death (>12 months) |
| Dose-Finding part: Safety (incidence of adverse events) | From baseline to disease progression or death (>12 months) |
Countries
Denmark, France, Switzerland, United Kingdom
Outcome results
None listed