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

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.

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