Clinical Trial Finder

DISEASE CHARACTERISTICS:

• - Histologically confirmed supratentorial malignant primary glioma of one of the following subtypes: - Glioblastoma multiforme.

• - Anaplastic astrocytoma.

• - Anaplastic oligodendroglioma.

• - Mixed malignant glioma.

• - Original histology of low-grade glioma allowed if subsequent histological confirmation of malignant glioma.

• - Measurable recurrent or residual primary disease by MRI.

• - Lesions with clearly defined margins.

• - Evidence of tumor recurrence or progression by MRI or CT scan.

• - Confirmation of true progressive disease by PET or thallium scan, magnetic resonance spectroscopy, or surgical documentation after prior interstitial brachytherapy or stereotactic radiosurgery.

• - No more than 3 relapses after prior chemotherapy/cytotoxic therapy (including polifeprosan 20 with carmustine implant) for phase I and no more than 2 relapses for phase II.

PATIENT CHARACTERISTICS: Age:

• - 18 and over.

Performance status:

• - Karnofsky 60-100% Life expectancy: - Not specified.

Hematopoietic:

• - WBC at least 3,000/mm^3.

• - Absolute neutrophil count at least 1,500/mm^3.

• - Platelet count at least 100,000/mm^3.

• - Hemoglobin at least 10 g/dL.

Hepatic:

• - Bilirubin no greater than 1.5 mg/dL.

• - SGOT no greater than 2 times upper limit of normal.

Renal:

• - Creatinine no greater than 1.5 mg/dL.

Cardiovascular:

• - No uncontrolled hypertension, unstable angina, or symptomatic congestive heart failure.

• - No myocardial infarction within the past 6 months.

• - No serious uncontrolled cardiac arrhythmia.

Other:

• - Not pregnant or nursing.

• - Negative pregnancy test.

• - Fertile patients must use effective contraception.

• - No mental incapacitation.

• - HIV negative.

• - No AIDS-related disease.

• - No significant ongoing alcoholism or substance abuse.

• - No severe nonmalignant systemic disease.

• - No active infection.

• - No other severe disease that would preclude study.

PRIOR CONCURRENT THERAPY: Biologic therapy:

• - At least 1 week since prior interferon or thalidomide and recovered.

• - No concurrent anticancer immunotherapy.

• - No concurrent sargramostim (GM-CSF) - No concurrent prophylactic filgrastim (G-CSF) during first course of study therapy.

Chemotherapy:

• - See Disease Characteristics.

• - Recovered from prior chemotherapy.

• - At least 2 weeks since prior vincristine.

• - At least 3 weeks since prior procarbazine.

• - At least 4 weeks since prior cytotoxic chemotherapy (6 weeks for nitrosourea) - Prior radiosensitizers allowed.

• - No prior temozolomide or irinotecan.

• - No other concurrent anticancer chemotherapy.

Endocrine therapy:

• - At least 1 week since prior tamoxifen and recovered.

• - No concurrent anticancer hormonal therapy.

• - Phase II: - Non-increasing dose of corticosteroids allowed.

Radiotherapy:

• - See Disease Characteristics.

• - At least 4 weeks since prior radiotherapy and recovered.

• - No concurrent anticancer radiotherapy.

Surgery:

• - See Disease Characteristics.

• - At least 1-3 weeks since prior surgical resection and recovered.

Other:

• - At least 1 week since prior noncytotoxic agents (e.g., isotretinoin) and recovered.

• - Concurrent enzyme-inducing anti-epileptic drugs with or without steroids allowed.

• - No concurrent valproic acid as a single agent.

• - No concurrent medication that would preclude study (e.g., nonsteroidal immunosuppressive agents) - No other concurrent investigational drugs.

- No concurrent participation in other clinical study

OBJECTIVES:

• - Determine the maximum tolerated dose and dose-limiting toxicity of irinotecan when administered with temozolomide in patients with recurrent malignant glioma.

• - Determine the safety profile of this regimen in this patient population.

• - Determine the efficacy of this treatment regimen as measured by 6-month progression-free survival and objective tumor response in these patients.

• - Characterize the pharmacokinetics of this treatment regimen in these patients.

• - Determine the antitumor activity of this treatment regimen in these patients.

OUTLINE: This is a multicenter, dose-escalation study of irinotecan. Patients are stratified according to concurrent enzyme-inducing anti-epileptic drugs (EIAEDs) (e.g., phenytoin, phenobarbital, carbamazepine, or primidone) (yes vs.#46;no). In phase I of the study, patients receive oral temozolomide on days 1-5 and irinotecan IV over 90 minutes on days 1 and 14. Treatment continues every 28 days for up to 1 year in the absence of disease progression or unacceptable toxicity. Patients concurrently on EIAEDs undergo dose escalation of irinotecan. Cohorts of 3 to 6 patients receive escalating doses of irinotecan until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 6 patients experience dose-limiting toxicity. In phase II of the study, patients receive the same treatment as in phase I at the MTD. Patients are followed every 2 months for 1 year, every 3 months for 1 year, every 4 months for 1 year, every 6 months until progression, and then every 4 months for survival. PROJECTED ACCRUAL: A total of 30 patients will be accrued for phase I within 10 months and 48 patients will be accrued for phase II within 6-8 months.