A Phase I, Open Label Study of AT-101 Plus Radiotherapy and Temozolomide and of AT-101 Plus Adjuvant Temozolomide for Patients With Newly-Diagnosed Glioblastoma Multiforme
- Determine the maximum tolerated dose (MTD) of gossypol (AT-101) when administered with
radiotherapy (RT) and concurrent temozolomide (TMZ) in patients with newly diagnosed
- Determine the MTD of gossypol when administered with adjuvant TMZ after standard RT and
concurrent TMZ in these patients.
- Assess the toxicity of these treatment regimens.
- Assess and describe the pharmacokinetics of gossypol.
- Determine, preliminarily, the therapeutic activities of these regimens.
- Determine the relationship between these regimens and cellular and molecular features
identified in tumor biopsy specimens.
OUTLINE: This is a multicenter, open-label, nonrandomized, dose-escalation study of
gossypol. Patients are assigned to 1 of 2 treatment groups. Patients who participate in
group I are NOT eligible for group II.
- Group I: Patients receive oral gossypol and undergo radiotherapy once daily 5 days a
week for up to 6 weeks. Patients also receive oral temozolomide once daily for up to 6
weeks. Treatment continues in the absence of disease progression or unacceptable
- Group II: Patients receive oral temozolomide on days 1-5 and oral gossypol once daily
on days 1-21. Treatment repeats every 28 days for up to 6 courses in the absence of
disease progression or unacceptable toxicity.
Cohorts of 3-10 patients per treatment group receive escalating doses of gossypol until the
maximum tolerated dose (MTD) is determined. The MTD is defined as the dose at which 2 of 6
or 3 of 10 patients experience dose-limiting toxicity.
Patients undergo blood collection periodically for pharmacokinetic studies. Tumor tissue
samples are examined for biomarkers including, but not limited to, Bcl-2 family protein
expression (e.g., Bcl-2, Bcl-xL, MCl-1, Bax, Bak, and BH3 domain), MGMT gene methylation
status, and gene expression array.
After completion of study treatment, patients are followed every 2 months.
PROJECTED ACCRUAL: A total of 50 patients will be accrued for this study.
Allocation: Non-Randomized, Masking: Open Label, Primary Purpose: Treatment
Maximum tolerated dose
John Fiveash, MD
University of Alabama at Birmingham
United States: Food and Drug Administration
|Abramson Cancer Center of the University of Pennsylvania||Philadelphia, Pennsylvania 19104-4283|
|Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins||Baltimore, Maryland 21231-2410|
|Cleveland Clinic Taussig Cancer Center||Cleveland, Ohio 44195|
|Josephine Ford Cancer Center at Henry Ford Hospital||Detroit, Michigan 48202|
|Winship Cancer Institute of Emory University||Atlanta, Georgia 30322|
|Wake Forest University Comprehensive Cancer Center||Winston-Salem, North Carolina 27157-1096|
|H. Lee Moffitt Cancer Center and Research Institute at University of South Florida||Tampa, Florida 33612|
|Lurleen Wallace Comprehensive Cancer at University of Alabama - Birmingham||Birmingham, Alabama 35294|