NCT00390403

Gossypol (AT-101) and Temozolomide With or Without Radiation Therapy in Treating Patients With Newly Diagnosed Glioblastoma Multiforme

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

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 50 (estimated)
• Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

RATIONALE: Drugs used in chemotherapy, such as gossypol and temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Gossypol may help temozolomide work better by making tumor cells more sensitive to the drug. Gossypol may also make tumor cells more sensitive to radiation therapy. Giving gossypol and temozolomide together with radiation therapy may kill more tumor cells. PURPOSE: This phase I trial is studying the side effects and best dose of gossypol when given together with temozolomide with or without radiation therapy in treating patients with newly diagnosed glioblastoma multiforme.

Detailed description

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.

Conditions

• Brain and Central Nervous System Tumors

Interventions

Type	Name	Description
DRUG	R-(-)-gossypol acetic acid
DRUG	temozolomide
GENETIC	gene expression analysis
GENETIC	mutation analysis
GENETIC	protein expression analysis
OTHER	laboratory biomarker analysis
OTHER	pharmacological study
PROCEDURE	adjuvant therapy
RADIATION	radiation therapy

Timeline

• Start date: 2007-02-01
• Primary completion: 2009-06-01
• First posted: 2006-10-19
• Last updated: 2012-05-03

Locations

8 sites across 1 country: United States