Temozolomide Plus Irinotecan in Treating Patients With Recurrent 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/II trial to study the effectiveness of temozolomide plus irinotecan in treating patients who have recurrent malignant glioma.

OBJECTIVES:

* Determine the maximum tolerated dose and dose-limiting toxicity of irinotecan when administered with temozolomide in patients with recurrent malignant glioma.
* Determine the safety profile of this regimen in this patient population.
* Determine the efficacy of this treatment regimen as measured by 6-month progression-free survival and objective tumor response in these patients.
* Characterize the pharmacokinetics of this treatment regimen in these patients.
* Determine the antitumor activity of this treatment regimen in these patients.

OUTLINE: This is a multicenter, dose-escalation study of irinotecan. Patients are stratified according to concurrent enzyme-inducing anti-epileptic drugs (EIAEDs) (e.g., phenytoin, phenobarbital, carbamazepine, or primidone) (yes vs no).

In phase I of the study, patients receive oral temozolomide on days 1-5 and irinotecan IV over 90 minutes on days 1 and 14. Treatment continues every 28 days for up to 1 year in the absence of disease progression or unacceptable toxicity.

Patients concurrently on EIAEDs undergo dose escalation of irinotecan. Cohorts of 3 to 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 3 or 6 patients experience dose-limiting toxicity.

In phase II of the study, patients receive the same treatment as in phase I at the MTD.

Patients are followed every 2 months for 1 year, every 3 months for 1 year, every 4 months for 1 year, every 6 months until progression, and then every 4 months for survival.

PROJECTED ACCRUAL: A total of 30 patients will be accrued for phase I within 10 months and 48 patients will be accrued for phase II within 6-8 months.

Eligibility Criteria:
DISEASE CHARACTERISTICS:

* Histologically confirmed supratentorial malignant primary glioma of one of the following subtypes:

  * Glioblastoma multiforme
  * Anaplastic astrocytoma
  * Anaplastic oligodendroglioma
  * Mixed malignant glioma
* Original histology of low-grade glioma allowed if subsequent histological confirmation of malignant glioma
* Measurable recurrent or residual primary disease by MRI

  * Lesions with clearly defined margins
* Evidence of tumor recurrence or progression by MRI or CT scan
* Confirmation of true progressive disease by PET or thallium scan, magnetic resonance spectroscopy, or surgical documentation after prior interstitial brachytherapy or stereotactic radiosurgery
* No more than 3 relapses after prior chemotherapy/cytotoxic therapy (including polifeprosan 20 with carmustine implant) for phase I and no more than 2 relapses for phase II

PATIENT CHARACTERISTICS:

Age:

* 18 and over

Performance status:

* Karnofsky 60-100%

Life expectancy:

* Not specified

Hematopoietic:

* WBC at least 3,000/mm\^3
* 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 no greater than 1.5 mg/dL
* SGOT no greater than 2 times upper limit of normal

Renal:

* Creatinine no greater than 1.5 mg/dL

Cardiovascular:

* No uncontrolled hypertension, unstable angina, or symptomatic congestive heart failure
* No myocardial infarction within the past 6 months
* No serious uncontrolled cardiac arrhythmia

Other:

* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception
* No mental incapacitation
* HIV negative
* No AIDS-related disease
* No significant ongoing alcoholism or substance abuse
* No severe nonmalignant systemic disease
* No active infection
* No other severe disease that would preclude study

PRIOR CONCURRENT THERAPY:

Biologic therapy:

* At least 1 week since prior interferon or thalidomide and recovered
* No concurrent anticancer immunotherapy
* No concurrent sargramostim (GM-CSF)
* No concurrent prophylactic filgrastim (G-CSF) during first course of study therapy

Chemotherapy:

* See Disease Characteristics
* Recovered from prior chemotherapy
* At least 2 weeks since prior vincristine
* At least 3 weeks since prior procarbazine
* At least 4 weeks since prior cytotoxic chemotherapy (6 weeks for nitrosourea)
* Prior radiosensitizers allowed
* No prior temozolomide or irinotecan
* No other concurrent anticancer chemotherapy

Endocrine therapy:

* At least 1 week since prior tamoxifen and recovered
* No concurrent anticancer hormonal therapy
* Phase II:

  * Non-increasing dose of corticosteroids allowed

Radiotherapy:

* See Disease Characteristics
* At least 4 weeks since prior radiotherapy and recovered
* No concurrent anticancer radiotherapy

Surgery:

* See Disease Characteristics
* At least 1-3 weeks since prior surgical resection and recovered

Other:

* At least 1 week since prior noncytotoxic agents (e.g., isotretinoin) and recovered
* Concurrent enzyme-inducing anti-epileptic drugs with or without steroids allowed
* No concurrent valproic acid as a single agent
* No concurrent medication that would preclude study (e.g., nonsteroidal immunosuppressive agents)
* No other concurrent investigational drugs
* No concurrent participation in other clinical study