Carmustine Wafers Plus Irinotecan in Treating Patients With Recurrent Supratentorial High Grade Gliomas

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 carmustine wafers plus irinotecan in treating patients with recurrent supratentorial high grade gliomas.

Detailed Description
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OBJECTIVES: Define the maximum tolerated dose of irinotecan given in combination with Gliadel wafers (carmustine) in patients with recurrent glioblastoma multiforme, anaplastic astrocytoma, or gliosarcoma. Define the toxicity of irinotecan given in combination with Gliadel wafers in these patients. OUTLINE: This is a dose escalation study. All patients undergo surgical resection. At the time of surgery, up to eight Gliadel wafers (containing carmustine) are implanted in the resected tumor cavity. Cohorts of 3 patients each receive escalating doses of irinotecan IV over 90 minutes once weekly within 3 weeks after Gliadel wafer implantation. One course of treatment consists of 4 weeks of irinotecan and 2 weeks of rest. If 1 patient experiences dose limiting toxicity (DLT) at a dose level, an additional 3 patients are entered at that same dose level. If 2 patients experience DLT, the maximum tolerated dose (MTD) has been surpassed and a total of 6 patients are treated at the previous dose level. The MTD is defined as the highest dose in which no more than 1 of 6 patients experiences DLT. Treatment continues for up to 12 courses in the absence of unacceptable toxicity and disease progression. Patients are followed for at least 4 months. PROJECTED ACCRUAL: Approximately 18 patients will be accrued into this study over 9 months.

Official Title
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Phase I Treatment of Adults With Recurrent Supratentorial High Grade Glioma With Gliadel Wafers Plus Irinotecan (CPT-11)

Conditions
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Brain and Central Nervous System Tumors

Intervention / Treatment
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* Drug: carmustine
* Drug: irinotecan hydrochloride
* Drug: polifeprosan 20 with carmustine implant
* Procedure: surgical procedure


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed recurrent supratentorial glioblastoma multiforme, anaplastic astrocytoma, or gliosarcoma Must be able to undergo surgical resection At least 1 bidimensionally measurable lesion documented on Gd-MRI within 72 hours after surgical implantation of Gliadel wafers Not requiring immediate radiotherapy PATIENT CHARACTERISTICS: Age: 18 and over Performance status: Karnofsky 70-100% Life expectancy: Greater than 12 weeks Hematopoietic: Absolute neutrophil count at least 1,500/mm^3 Platelet count at least 125,000/mm^3 Hematocrit at least 29% Hepatic: Bilirubin less than 1.5 times upper limit of normal (ULN) SGOT or SGPT less than 2.5 times ULN Alkaline phosphatase less than 2 times ULN Renal: BUN less than 1.5 times ULN Creatinine less than 1.5 times ULN Neurological: Must be neurologically stable Other: HIV negative No AIDS-related illness No nonmalignant systemic disease that would make patient a poor medical risk No acute infection requiring intravenous antibiotics Not pregnant or nursing Negative pregnancy test 24 hours prior to study Effective contraception required of all fertile patients PRIOR CONCURRENT THERAPY: Biologic therapy: Not specified Chemotherapy: No prior irinotecan At least 6 weeks since chemotherapy unless there is unequivocal evidence of tumor progression after chemotherapy Endocrine therapy: At least 1 week of nonincreasing dose of steroids prior to study Radiotherapy: At least 6 weeks since radiotherapy unless there is unequivocal evidence of tumor progression after radiotherapy No concurrent radiotherapy Surgery: Not specified

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: carmustine|nan|
|Drug: irinotecan hydrochloride|nan|
|Drug: polifeprosan 20 with carmustine implant|nan|
|Procedure: surgical procedure|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 brain stem glioma, adult glioblastoma, adult anaplastic astrocytoma, adult mixed glioma, adult giant cell glioblastoma, adult gliosarcoma