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

Purpose

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.

Condition	Intervention	Phase
Glioblastoma Multiforme	Drug: RO5323441 + bevacizumab [Avastin] Drug: bevacizumab [Avastin]	Phase 1

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

Resource links provided by NLM:

Drug Information available for: Bevacizumab

U.S. FDA Resources

Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:

Dose-Finding Part: Dose limiting toxicity [ Time Frame: Day 28 ] [ Designated as safety issue: No ]
Efficacy-Finding part: Progression-free survival [ Time Frame: From baseline to disease progression or death (>12 months) ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Dose-Finding part: Pharmacokinetics of RO5323441 and Avastin when combined [ Time Frame: From baseline to disease progression or death (>12 months) ] [ Designated as safety issue: No ]
Dose-Finding part: Safety (incidence of adverse events) [ Time Frame: From baseline to disease progression or death (>12 months) ] [ Designated as safety issue: No ]
Dose-Finding part: Efficacy (tumor response according to Response Assessment in Neurooncology (RANO) criteria [ Time Frame: From baseline to disease progression or death (>12 months) ] [ Designated as safety issue: No ]
Dose-Finding part: Glioblastoma biomarker [ Time Frame: From baseline to disease progression or death (>12 months) ] [ Designated as safety issue: No ]
Efficacy-Finding part: Overall Response Rate [ Time Frame: From baseline to disease progression or death (>12 months) ] [ Designated as safety issue: No ]
Efficacy-Finding part: Disease Control Rate [ Time Frame: From baseline to disease progression or death (>12 months) ] [ Designated as safety issue: No ]
Efficacy-Finding part: Duration of Response [ Time Frame: From baseline to disease progression or death (>12 months) ] [ Designated as safety issue: No ]
Efficacy-Finding part: Progression-free survival [ Time Frame: From baseline to disease progression or death (>12 months) ] [ Designated as safety issue: No ]
Efficacy-Finding part: Overall Survival [ Time Frame: From baseline to disease progression or death (>12 months) ] [ Designated as safety issue: No ]
Efficacy-Finding part: Safety (incidence of adverse events) [ Time Frame: From baseline to disease progression or death (>12 months) ] [ Designated as safety issue: No ]
Efficacy-Finding part: Glioblastoma biomarker [ Time Frame: From baseline to disease progression or death (>12 months) ] [ Designated as safety issue: No ]
Efficacy-Finding part: Pharmacokinetics (serum levels) of RO5323441 and Avastin when combined [ Time Frame: From baseline to disease progression or death (>12 months) ] [ Designated as safety issue: No ]

Enrollment:	22
Study Start Date:	May 2011
Estimated Study Completion Date:	April 2013
Estimated Primary Completion Date:	April 2013 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: 1	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
Experimental: 2	Drug: bevacizumab [Avastin] Efficacy-Finding part: 10 mg/kg intravenously once every two weeks

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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)

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01308684

Locations

Denmark

København, Denmark, 2100
France

Marseille, France, 13385
Switzerland

Zürich, Switzerland, 8091
United Kingdom

Manchester, United Kingdom, M2O 4BX

Sponsors and Collaborators

Hoffmann-La Roche

Investigators

Study Director:

Clinical Trials

Hoffmann-La Roche

More Information

No publications provided

Responsible Party:	Hoffmann-La Roche
ClinicalTrials.gov Identifier:	NCT01308684 History of Changes
Other Study ID Numbers:	BP25389, 2010-021795-29
Study First Received:	March 2, 2011
Last Updated:	April 29, 2013
Health Authority:	France: Ministry of Health

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
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Pharmacologic Actions
Growth Inhibitors
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on May 23, 2013