Clinical Trial Finder

DISEASE CHARACTERISTICS:

• - Histologically confirmed supratentorial grade IV astrocytoma (glioblastoma multiforme) - Meets 1 of the following criteria: - Completed surgery within the past 6 weeks (group I) - Received radiotherapy and concomitant temozolomide at least 4 weeks but no more than 7 weeks prior to start of study treatment (group II) - Must be on a stable corticosteroid regimen (no increase for 5 days) PATIENT CHARACTERISTICS: - Karnofsky performance status 60-100% - Hemoglobin ≥ 10 g/dL.

• - Absolute neutrophil count ≥ 1,500/mm³ - Platelet count ≥ 100,000/mm³ - Creatinine ≤1.5 mg/dL.

• - Bilirubin ≤ 1.5 mg/dL.

• - ALT and AST ≤ 2.5 times upper limit of normal.

• - Not pregnant or nursing.

• - Negative pregnancy test.

• - Fertile patients must use effective contraception during and for 2 months after completion of study treatment.

• - Mini Mental State Exam score ≥ 15.

• - Must be able to swallow and retain oral medication.

• - No serious concurrent infection or medical illness that would preclude study participation.

• - No other malignancy within the past 5 years, except for curatively treated carcinoma in situ or basal cell carcinoma of the skin.

• - No sensory neuropathy ≥ grade 2.

• - No allergies to gossypol.

• - No symptomatic hypercalcemia or hypercalcemia > grade 2.

• - No gastrointestinal disease including any of the following: - Malabsorption syndrome.

• - Disease significantly affecting gastrointestinal function.

• - Ulcerative colitis.

• - Inflammatory bowel disease.

• - Partial or complete small bowel obstruction.

PRIOR CONCURRENT THERAPY:

• - See Disease Characteristics.

• - Recovered from the immediate postoperative period.

• - No prior radiotherapy, chemotherapy, immunotherapy, therapy with biologic agents (including immunotoxins, immunoconjugates, antisense agents, peptide-receptor antagonists, interferons, interleukins, tumor-infiltrating lymphocyte therapy, lymphokine-activated killer cells or gene therapy), or hormonal therapy for this brain tumor (group I) - Prior glucocorticoid therapy allowed.

• - No prior polifeprosan 20 with carmustine implant (Gliadel wafers) (group I) - No prior gossypol.

• - No prior radiosurgery or brachytherapy.

• - No prior resection of the stomach or small intestine.

• - No other concurrent anticancer therapy (i.e., chemotherapeutics or investigational agents) - No concurrent cytochrome p450 enzyme-inducing anticonvulsant drugs.

• - No concurrent prophylactic filgrastim (G-CSF) - No concurrent iron supplements.

• - Nutritional supplements containing iron allowed.

• - No concurrent intensity-modulated radiotherapy.

- No concurrent electron, particle, implant, or stereotactic radiosurgery boost

OBJECTIVES: Primary.

• - Determine the maximum tolerated dose (MTD) of gossypol (AT-101) when administered with radiotherapy (RT) and concurrent temozolomide (TMZ) in patients with newly diagnosed glioblastoma multiforme.

• - Determine the MTD of gossypol when administered with adjuvant TMZ after standard RT and concurrent TMZ in these patients.

Secondary.

• - 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 toxicity.

• - 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.