Temozolomide Plus Irinotecan in Treating Patients With Recurrent Malignant Glioma

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells. PURPOSE: Phase I/II trial to study the effectiveness of temozolomide plus irinotecan in treating patients who have recurrent malignant glioma.

Detailed Description
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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 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.

Official Title
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Phase I-II Trial of CPT-11 and Temozolomide (Temodar) in Patients With Recurrent Malignant Glioma

Conditions
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Brain and Central Nervous System Tumors

Intervention / Treatment
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* Drug: irinotecan hydrochloride
* Drug: temozolomide


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 120 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: irinotecan hydrochloride|nan|
|Drug: temozolomide|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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recurrent adult brain tumor, adult glioblastoma, adult anaplastic astrocytoma, adult anaplastic oligodendroglioma, adult mixed glioma, adult giant cell glioblastoma, adult gliosarcoma