Thalidomide and Irinotecan in Treating Patients With Glioblastoma Multiforme Who Have Undergone Radiation Therapy

Study Overview
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Brief Summary
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RATIONALE: Thalidomide may stop the growth of glioblastoma multiforme by stopping blood flow to the tumor. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining thalidomide with irinotecan may kill any tumor cells remaining after radiation therapy. PURPOSE: Phase II trial to study the effectiveness of combining thalidomide with irinotecan in treating patients who have glioblastoma multiforme that has been treated with radiation therapy.

Detailed Description
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OBJECTIVES: Determine the response rate of patients with glioblastoma multiforme treated with thalidomide and irinotecan after radiotherapy. Determine the preliminary efficacy of this regimen in these patients. Determine the disease-free survival and overall survival of patients treated with this regimen. Determine the toxicity of this regimen in these patients. Assess the quality of life of patients treated with this regimen. OUTLINE: Beginning 2-4 weeks after completion of radiotherapy, patients receive irinotecan IV over 90 minutes on day 1. Patients also receive oral thalidomide daily. Treatment repeats every 21 days for at least 3 courses in the absence of disease progression or unacceptable toxicity. Quality of life is assessed at baseline, 1 week after the first course, prior to all subsequent courses, and then after course 6. Patients are followed for 5 years. PROJECTED ACCRUAL: A total of 9-24 patients will be accrued for this study.

Official Title
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A Phase II Study Of Thalidomide And CPT-11 (IRINOTECAN) Following Radiotherapy For Glioblastoma Multiforme

Conditions
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Brain and Central Nervous System Tumors

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


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed glioblastoma multiforme (GBM) Recurrent disease allowed Evaluable disease on contrast-enhanced MRI Prior external beam radiotherapy required PATIENT CHARACTERISTICS: Age: 18 and over Performance status: Karnofsky 60-100% Life expectancy: Not specified Hematopoietic: Absolute neutrophil count at least 1,500/mm^3 Platelet count at least 100,000/mm^3 Hepatic: Bilirubin no greater than 1.5 times upper limit of normal (ULN) AST or ALT no greater than 5 times ULN Renal: Creatinine no greater than 1.5 times ULN OR Creatinine clearance at least 60 mL/min Cardiovascular: No significant cardiac disease No uncontrolled high blood pressure No unstable angina No congestive heart failure No myocardial infarction within the past 3 months No serious cardiac arrhythmias Gastrointestinal: Able to take oral medication No gastrointestinal abnormalities No requirement for IV alimentation No active peptic ulcer disease Other: No active infection No serious uncontrolled medical disorder No dementia or significantly altered mental status that would preclude study No known hypersensitivity to irinotecan or thalidomide Not pregnant or nursing Negative pregnancy test Fertile patients must use 2 forms of effective contraception, including 1 highly effective method, at least 1 month before, during, and for 1 month after study PRIOR CONCURRENT THERAPY: Biologic therapy: No prior thalidomide Chemotherapy: No prior irinotecan At least 4 weeks since other prior chemotherapy (and demonstrated evidence of disease progression or relapse) Endocrine therapy: Concurrent corticosteroids allowed if on a stable or decreasing dose for at least 1 week prior to study No concurrent hormonal therapy for GBM Radiotherapy: See Disease Characteristics No concurrent radiotherapy for GBM Surgery: No prior surgical procedures affecting absorption Other: No other concurrent anticancer investigational agents for GBM No concurrent cytochrome P450 inhibitors, including the following: Nefazodone Fluvoxamine Fluoxetine Sertraline Paroxetine Venlafaxine Ketoconazole Itraconazole Fluconazole Cimetadine Clarithromycin Diltiazem Erythromycin Protease inhibitors

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
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: irinotecan hydrochloride|350 or 700 mg/m2 IV every 3 weeks|
|Drug: thalidomide|400mg/day oral|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response | To evaluate the response rate and hence preliminary efficacy of Irinotecan and Thalidomide following radiotherapy in the treatment of newly diagnosed or relapsed glioblastoma multiforme. | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Toxicity / QOL / Survival | To evaluate 1) toxicity 2) quality of life 3) disease free survival and 4) overall survival of patients treated with this combination. | 2 years | 

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