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

Glioblastoma Multiforme Clinical Trial

Official title:

Open-label, Combined Dose-finding (Phase I) and Efficacy-finding (Phase II) Study of RO5323441 in Combination With Bevacizumab for Patients With Recurrent Glioblastoma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01308684
• Other study ID #: BP25389
• Secondary ID: 2010-021795-29
• Status: Completed
• Phase: Phase 1
• First received: March 2, 2011
• Last updated: November 1, 2016
• Start date: May 2011
• Est. completion date: February 2013

Study information

• Verified date: November 2016
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Ministry of Health
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 22
• Est. completion date: February 2013
• Est. primary completion date: February 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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)

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Glioblastoma
• Glioblastoma Multiforme

Intervention

Drug:
• RO5323441 + 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
• bevacizumab [Avastin]
Efficacy-Finding part: 10 mg/kg intravenously once every two weeks

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

Denmark,  France,  Switzerland,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Dose-Finding Part: Dose limiting toxicity		Day 28	No
Primary	Efficacy-Finding part: Progression-free survival		From baseline to disease progression or death (>12 months)	No
Secondary	Dose-Finding part: Pharmacokinetics of RO5323441 and Avastin when combined		From baseline to disease progression or death (>12 months)	No
Secondary	Dose-Finding part: Safety (incidence of adverse events)		From baseline to disease progression or death (>12 months)	No
Secondary	Dose-Finding part: Efficacy (tumor response according to Response Assessment in Neurooncology (RANO) criteria		From baseline to disease progression or death (>12 months)	No
Secondary	Dose-Finding part: Glioblastoma biomarker		From baseline to disease progression or death (>12 months)	No
Secondary	Efficacy-Finding part: Overall Response Rate		From baseline to disease progression or death (>12 months)	No
Secondary	Efficacy-Finding part: Disease Control Rate		From baseline to disease progression or death (>12 months)	No
Secondary	Efficacy-Finding part: Duration of Response		From baseline to disease progression or death (>12 months)	No
Secondary	Efficacy-Finding part: Progression-free survival		From baseline to disease progression or death (>12 months)	No
Secondary	Efficacy-Finding part: Overall Survival		From baseline to disease progression or death (>12 months)	No
Secondary	Efficacy-Finding part: Safety (incidence of adverse events)		From baseline to disease progression or death (>12 months)	No
Secondary	Efficacy-Finding part: Glioblastoma biomarker		From baseline to disease progression or death (>12 months)	No
Secondary	Efficacy-Finding part: Pharmacokinetics (serum levels) of RO5323441 and Avastin when combined		From baseline to disease progression or death (>12 months)	No