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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT01308684
First received: March 2, 2011
Last updated: November 3, 2014
Last verified: November 2014
  Purpose

This open-label, multicenter study will evaluate the safety and efficacy of RO53 23441 in combination with Avastin (bevacizumab) in patients with recurrent gliob lastoma. 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 establish ed 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 Ava stin on the study until evidence of progressive disease or unacceptable adverse events happen. In the efficacy-finding part, patients will receive study treatme nt until disease progression or death.


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


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
Study Completion Date: February 2013
Primary Completion Date: February 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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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: November 3, 2014
Health Authority: France: Ministry of Health

Additional relevant MeSH terms:
Glioblastoma
Astrocytoma
Glioma
Neoplasms
Neoplasms by Histologic Type
Neoplasms, Germ Cell and Embryonal
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Bevacizumab
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Antineoplastic Agents
Growth Inhibitors
Growth Substances
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on November 20, 2014