Carboplatin Plus Irinotecan in Treating Patients With Glioblastoma Multiforme

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 II trial to study the effectiveness of combining carboplatin with irinotecan in treating patients who have glioblastoma multiforme.

Detailed Description
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OBJECTIVES: Determine the maximum tolerated dose (MTD) of carboplatin and irinotecan in patients with glioblastoma multiforme. (Phase I closed to accrual as of 6/24/02) Determine the toxic effects of this regimen in these patients. Determine the objective response in patients treated with the established MTD of this regimen. Determine time to tumor progression and survival of patients treated with this regimen. OUTLINE: This is a dose-escalation study. Patients in the phase II portion of the study are stratified according to age (under 60 vs 60 and over), ECOG performance status (0-1 vs 2), and extent of resection (total vs subtotal). (Phase I closed to accrual as of 6/24/02) Within 4 weeks of surgery, patients receive carboplatin IV over 30 minutes followed by irinotecan IV over 90 minutes on day 1. Treatment repeats every 4 weeks for a maximum of 6 courses in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of carboplatin and irinotecan until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Once the MTD is determined, additional patients are accrued to receive carboplatin and irinotecan at the recommended phase II dose. (Phase I closed to accrual as of 6/24/02) After chemotherapy, all patients undergo radiotherapy. Patients are followed for 30 days. PROJECTED ACCRUAL: A total of 24-107 patients (3-54 for phase I and 21-53 for phase II) will be accrued for this study. (Phase I closed to accrual as of 6/24/02)

Official Title
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A Phase I/II Trial of CPT-11 With Carboplatin in Patients With Glioblastoma Multiforme Prior to Radiation Therapy

Conditions
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Brain and Central Nervous System Tumors

Intervention / Treatment
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* Drug: carboplatin
* Drug: irinotecan hydrochloride
* Radiation: radiation therapy


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed glioblastoma multiforme Measurable disease No CNS metastases or carcinomatous meningitis PATIENT CHARACTERISTICS: Age: 18 and over Performance status: ECOG 0-2 OR Karnofsky 70-100% Life expectancy: At least 12 weeks Hematopoietic: Granulocyte count greater than 1,500/mm^3 Platelet count greater than 100,000/mm^3 Hemoglobin at least 9.0 g/dL Hepatic: Bilirubin no greater than 1.5 mg/dL SGOT no greater than 3 times upper limit of normal (ULN) (5 times ULN if liver involvement) No known Gilbert's syndrome Renal: Creatinine no greater than 1.5 mg/dL Cardiovascular: No myocardial infarction within the past 6 months No congestive heart failure requiring therapy Other: HIV negative No active or uncontrolled infection No psychiatric disorder that would preclude study No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer or carcinoma in situ of the cervix No uncontrolled diabetes mellitus (i.e., random blood sugar of 200 mg or more) No other severe disease that would preclude study Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception PRIOR CONCURRENT THERAPY: Biologic therapy: No prior immunotherapy or biologic therapy No concurrent sargramostim (GM-CSF) No concurrent filgrastim (G-CSF) with course 1 No concurrent immunotherapy Chemotherapy: No prior chemotherapy No other concurrent chemotherapy Endocrine therapy: Must have maintained a stable or decreasing dose of corticosteroids for 2 weeks prior to study Concurrent corticosteroids for cerebral edema allowed No concurrent anticancer hormonal therapy Radiotherapy: No prior radiotherapy No concurrent radiotherapy Surgery: At least 2 weeks since prior surgery Other: No other concurrent investigational agent or participation on any other clinical study No concurrent immunosuppressive drugs No concurrent phenobarbital or valproic acid No concurrent anticonvulsants except carbamazepine or gabapentin No concurrent prochlorperazine on day of irinotecan treatment

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: carboplatin|nan|
|Drug: irinotecan hydrochloride|nan|
|Radiation: radiation therapy|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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adult glioblastoma, adult giant cell glioblastoma, adult gliosarcoma