Clinical trial NCT01308684: A Dose- and Efficacy-Finding Study of RO5323441 in Combination With Avastin (Bevacizumab) in Patients With Recurrent Glioblastoma
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Glioblastoma Multiforme
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2011-03-04
Enrollment: 22
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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)

Primary outcomes:
measure: Dose-Finding Part: Dose limiting toxicity
timeFrame: Day 28
measure: Efficacy-Finding part: Progression-free survival
timeFrame: From baseline to disease progression or death (>12 months)
Secondary outcomes:
measure: Dose-Finding part: Pharmacokinetics of RO5323441 and Avastin when combined
timeFrame: From baseline to disease progression or death (>12 months)
measure: Dose-Finding part: Safety (incidence of adverse events)
timeFrame: From baseline to disease progression or death (>12 months)
measure: Dose-Finding part: Efficacy (tumor response according to Response Assessment in Neurooncology (RANO) criteria
timeFrame: From baseline to disease progression or death (>12 months)
measure: Dose-Finding part: Glioblastoma biomarker
timeFrame: From baseline to disease progression or death (>12 months)
measure: Efficacy-Finding part: Overall Response Rate
timeFrame: From baseline to disease progression or death (>12 months)
measure: Efficacy-Finding part: Disease Control Rate
timeFrame: From baseline to disease progression or death (>12 months)
measure: Efficacy-Finding part: Duration of Response
timeFrame: From baseline to disease progression or death (>12 months)
measure: Efficacy-Finding part: Progression-free survival
timeFrame: From baseline to disease progression or death (>12 months)
measure: Efficacy-Finding part: Overall Survival
timeFrame: From baseline to disease progression or death (>12 months)
measure: Efficacy-Finding part: Safety (incidence of adverse events)
timeFrame: From baseline to disease progression or death (>12 months)
measure: Efficacy-Finding part: Glioblastoma biomarker
timeFrame: From baseline to disease progression or death (>12 months)
measure: Efficacy-Finding part: Pharmacokinetics (serum levels) of RO5323441 and Avastin when combined
timeFrame: From baseline to disease progression or death (>12 months)
Other outcomes:
Locations:
city: København Ø
country: Denmark
city: Marseille
country: France
city: Zürich
country: Switzerland
city: Manchester
country: United Kingdom
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: