Clinical trial NCT00892177
Conditions: Glioblastoma Multiforme
Keywords: adult giant cell glioblastoma adult glioblastoma adult gliosarcoma adult mixed glioma recurrent adult brain tumor adult anaplastic oligodendroglioma adult oligodendroglioma adult anaplastic astrocytoma
Sponsor: Alliance for Clinical Trials in Oncology
Start date: 2009-10-01; Completion date: 2019-07-01
Enrollment: 144 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
RATIONALE: Dasatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Bevacizumab may also block the growth of the tumor by blocking blood flow to the tumor. It is not yet known whether bevacizumab together with dasatinib are more effective than a placebo in treating patients with recurrent or progressive high-grade glioma or glioblastoma multiforme.

PURPOSE: This randomized phase I/II trial (Phase I completed) is studying the side effects and best dose of dasatinib when given together with bevacizumab and to see how well it works compared to placebo in treating patients with recurrent or progressive high-grade glioma or glioblastoma multiforme.

Detailed description:
OUTLINE: This is a multicenter, phase I, dose-escalation study (Phase I completed) of dasatinib followed by a phase II randomized study. Patients are grouped according to study (1 vs 2). Patients in the phase II portion are stratified according to age (\> 70 years of age vs ≤ 70 years of age), and ECOG performance status (0 vs 1 or 2).

Phase I: Patients receive bevacizumab IV over 30-90 minutes on day 1. Patients also receive oral dasatinib once or twice daily on days 1-14 until the maximum-tolerated dose (MTD) is determined. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity. (Phase I completed) Please see the Arms section for the Phase II treatment regimens.

OBJECTIVES:

PRIMARY OBJECTIVES:

1. Determine the maximum tolerated dose (MTD) of dasatinib in combination with bevacizumab in high grade glioma patients. (Phase I)
2. To assess the safety and adverse events of the dasatinib in combination with bevacizumab in this patient population. (Phase I)
3. To estimate the efficacy of the bevacizumab combination with dasatinib in recurrent glioblastoma multiforme as measured by progression free survival at six months and compare it with the efficacy of bevacizumab alone. (Phase II)

SECONDARY OBJECTIVES:

1. To describe the overall toxicity associated with the dasatinib/bevacizumab combination. (Phase I)
2. To describe any preliminary evidence of antitumor activity. (Phase I)
3. To assess the time to disease progression. (Phase II)
4. To assess the safety and toxicity of the bevacizumab combination with dasatinib in this patient population. (Phase II)
5. To estimate the efficacy of the bevacizumab combination with dasatinib in recurrent glioblastoma multiforme as measured by overall survival time and compare it with the efficacy of bevacizumab alone. (Phase II)
6. To assess the impact of the treatment on the patient's quality of life (QOL) using the overall score from the FACT-Br (Phase II)

Arms: arm 1: Patients receive bevacizumab on Day 1 and dasatinib on days 1-14. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity. arm 2: Patients receive bevacizumab on Day 1 and placebo on days 1-14. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.
Interventions: intervention 1: bevacizumab intervention 2: dasatinib intervention 3: placebo
Intervention descriptions: intervention 1: Given intravenously intervention 2: Given orally intervention 3: Given orally

Protocol documents: