Irinotecan Plus Temozolomide in Treating Patients With Recurrent Primary 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 trial to study the effectiveness of irinotecan plus temozolomide in treating patients who have recurrent primary malignant glioma.

Detailed Description
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OBJECTIVES: Determine the maximum tolerated dose of irinotecan administered in combination with temozolomide in patients with recurrent primary malignant glioma. Determine the toxicity of this combination therapy in these patients. OUTLINE: This is a dose escalation study of irinotecan. Patients are stratified according to concurrent anticonvulsants (Dilantin, Tegretol, or phenobarbital vs other anticonvulsants or none). Patients receive irinotecan IV over 90 minutes on days 1, 8, 15, and 22 and oral temozolomide on days 1-5. Treatment continues every 43 days in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 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 6 patients experience dose limiting toxicities. PROJECTED ACCRUAL: Not specified

Official Title
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Phase I Treatment of Adults With Primary Malignant Glioma With Irinotecan (CPT-11) (NSC- #6616348) Plus Temodar (NSC #362856)

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 recurrent primary malignant glioma Anaplastic astrocytoma Glioblastoma multiforme Anaplastic oligodendroglioma Gliosarcoma Anaplastic mixed oligoastrocytoma Measurable disease by MRI or CT No immediate radiotherapy required Neurologically stable for at least 2 weeks prior to study PATIENT CHARACTERISTICS: Age: 18 and over Performance status: Karnofsky 60-100% Life expectancy: Greater than 12 weeks Hematopoietic: 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 less than 1.5 times upper limit of normal (ULN) SGOT and SGPT less than 2.5 times ULN Alkaline phosphatase less than 2 times ULN Renal: Blood urea nitrogen and creatinine less than 1.5 times ULN Other: Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception HIV negative No other nonmalignant systemic disease No acute infection treated with IV antibiotics No frequent vomiting or other condition that would preclude oral medication administration (e.g., partial bowel obstruction) No other prior malignancies except surgically cured carcinoma in situ of the cervix or basal or squamous cell skin cancer PRIOR CONCURRENT THERAPY: Biologic therapy: No more than 1 prior biologic therapy regimen Chemotherapy: No more than 1 prior chemotherapy regimen At least 6 weeks since prior chemotherapy, unless evidence of disease progression No prior failure of irinotecan or temozolomide Endocrine therapy: Concurrent corticosteroids allowed Radiotherapy: See Disease Characteristics At least 6 weeks since prior radiotherapy, unless evidence of disease progression Surgery: At least 3 weeks since prior surgery, unless evidence of disease progression, and recovered Other: No concurrent immunosuppressive agents

Ages Eligible for Study
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Minimum Age: 18 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


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