This phase II trial is studying how well gossypol works in treating patients with progressive or recurrent glioblastoma multiforme. Gossypol may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
PRIMARY OBJECTIVES: I. To estimate the overall survival rate associated with AT-101 in treating adult patients with recurrent glioblastoma multiforme. SECONDARY OBJECTIVES: I. To assess and estimate the acute and late toxicities. II. Tumor response rate. III. To estimate 6-month progression free survival. IV. To explore associations of the clinical outcome (overall survival) among the changes of potential serum biomarkers, baseline tumor protein expression and gene methylation status. OUTLINE: This is a multicenter study. Patients receive oral R-(-)-gossypol once daily on days 1-21. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo tumor tissue and blood sample collection at baseline and periodically during study for biomarker correlative studies. Archived tumor tissue samples, if available, are analyzed for Bcl-2 family protein expression (e.g., Bcl-2, Bcl-xL, MCl-1, Bax, Bak, and BH3 domain for BH3 members only) and 06-methylguanine-DNA-methyltransferase (MGMT) gene methylation status. Blood samples are analyzed for apoptotic protein levels (Bcl-2) by enzyme-linked immunosorbent assay. After completion of study therapy, patients are followed every 2 months.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
56
Given PO
Correlative studies
University of Alabama at Birmingham
Birmingham, Alabama, United States
Moffitt Cancer Center
Tampa, Florida, United States
Johns Hopkins University
Baltimore, Maryland, United States
Massachusetts General Hospital
Boston, Massachusetts, United States
Overall Survival
The overall failure rate will be estimated along with 95% confidence intervals. A median time of survival will be estimated using standard methods.
Time frame: 4.5 years
Percent of Patients With Grade 3 and 4 Adverse Events Related to Treatment
The proportion of patients with serious or life threatening (grade 3 and 4) toxicities will be estimated using NCI CTCAE
Time frame: 3 years
Tumor Response Rate
Complete response Complete disappearance of all tumor on MRI scan, off all glucocorticoids with stable or improving neurological exam minimum of 4 wks Partial response Greater than or equal 50% reduction in tumor size on MRI, on sable or decreasing glucocorticoids with stable or improving neurological exam for a minimum of 4 wks. Progressive disease Progressive neurological abnormalities not explained by other causes or greater than 25% increase in size of tumor or if new lesion. Stable disease Clinical status and MRI does not qualify for complete response, partial response or progression
Time frame: 3 years
Progression-free Survival Rate, Defined as Patient Who is Alive and Disease Progression Free at the Time of 26-week (6 Months) From First Day of the Treatment
The probability of 6-month progression-free survival will be estimated using binomial distribution.
Time frame: 6 months
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Henry Ford Hospital
Detroit, Michigan, United States
Wake Forest University Health Sciences
Winston-Salem, North Carolina, United States
Cleveland Clinic Foundation
Cleveland, Ohio, United States
University of Pennsylvania
Philadelphia, Pennsylvania, United States