A Dose- and Efficacy-Finding Study of RO5323441 in Combination With Avastin (Bevacizumab) in Patients With Recurrent Glioblastoma

Phase 1

Completed

• Conditions: Glioblastoma Multiforme
• Interventions: Drug: bevacizumab [Avastin]; Drug: RO5323441 + bevacizumab [Avastin]

• Registration Number: NCT01308684
• Lead Sponsor: Hoffmann-La Roche

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2011-03-02
• Study First Submitted QC: 2011-03-02
• Study First Posted: 2011-03-04
• Study Start: 2011-05
• Primary Completion: 2013-02
• Study Completion: 2013-02
• Status Verified: 2016-11
• Last Update Submitted: 2016-11-01
• Last Update Posted: 2016-11-02

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 22

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

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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)

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
2	bevacizumab [Avastin]	-
1	RO5323441 + bevacizumab [Avastin]	-

Primary Outcome Measures

Name	Time	Method
Dose-Finding Part: Dose limiting toxicity	Day 28
Efficacy-Finding part: Progression-free survival	From baseline to disease progression or death (>12 months)

Secondary Outcome Measures

Name	Time	Method
Dose-Finding part: Pharmacokinetics of RO5323441 and Avastin when combined	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)
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)
Efficacy-Finding part: Progression-free survival	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)