Irinotecan Plus Temozolomide in Treating Patients With Recurrent Primary Malignant Glioma
Irinotecan Plus Temozolomide in Treating Patients With Recurrent Primary Malignant Glioma
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.
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
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