Clinical Trial: Avastin in Combination With Temozolomide for Unresectable or Multifocal GBMs and Gliosarcomas

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: Avastin in Combination With Temozolomide for Unresectable or Multifocal Glioblastoma Multiformes and Gliosarcomas

Brief Summary:

Primary objective- To determine efficacy of Avastin, 10 mg/kg every other week, in combination with standard 5-day temozolomide in terms of response rate.

Secondary objective- To determine safety of Avastin & Temozolomide in unresectable glioblastoma patients


Detailed Summary: Subjects have histologically confirmed WHO gr IV primary malignant glioma that is unresectable/multifocal. This is Phase II study where up to 41 subjects will receive up to 4 cycles of Avastin & Temozolomide. Avastin administered at 10 mg/kg every 14 days beginning a minimum of 7 days after biopsy/28 days after craniotomy. Temozolomide dosed at 200 mg/m2 daily for 5 days in 28-day cycle. Patients will receive up to 4 cycles of Avastin & Temozolomide, then proceed with standard XRT. Study will use 2-stage "minimax" study design in which 21 subjects are accrued during 1st stage, with possibility that additional 20 patients accrued during 2nd stage. In initial Phase I & II trials, 4 potential Avastin-associated safety signals were identified: hypertension, proteinuria, thromboembolic events, & hemorrhage. Avastin-associated adverse events in Phase III trials include congestive heart failure, GI perforations, wound healing complications, & arterial thromboembolic events. Most common toxicity associated with Temozolomide has been mild myelosuppression.
Sponsor: Duke University

Current Primary Outcome: Response Rate [ Time Frame: 4 months ]

The proportion of subjects with complete or partial response as determined by a modification of the RANO (Response Assessment in Neuro-Oncology) criteria. A confirmation of response was not required. Complete Response was defined as complete disappearance on MR/CT of all enhancing tumor and mass effect, off all corticosteroids (or receiving only adrenal replacement doses), accompanied by a stable or improving neurologic examination, and maintained for at least 4 weeks. Partial Response was defined as greater than or equal to 50% reduction in tumor size on MR/CT by bi-dimensional measurement, on a stable or decreasing dose of corticosteroids, accompanied by a stable or improving neurologic examination, and maintained for at least 4 weeks.


Original Primary Outcome: Response Rate [ Time Frame: 6 months ]

Current Secondary Outcome:

Original Secondary Outcome:

  • Progression-free survival [ Time Frame: 6 months ]
  • Incidence & severity of CNS hemorrhage & systemic hemorrhage. Incidence of > gr4 hematologic & > gr3 non-hematologic toxicities [ Time Frame: 6 months ]


Information By: Duke University

Dates:
Date Received: January 29, 2008
Date Started: August 2007
Date Completion:
Last Updated: May 20, 2013
Last Verified: September 2012