CCI-779 in Treating Patients With Malignant Glioma

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die.

PURPOSE: Phase I/II trial to study the effectiveness of CCI-779 in treating patients who have malignant glioma.

OBJECTIVES:

* Determine the maximum tolerated dose of CCI-779 in patients with malignant glioma.
* Determine the safety profile of this drug in these patients.
* Determine the pharmacokinetics of this drug in these patients.
* Determine the efficacy of this drug, in terms of survival and objective response, in these patients.

OUTLINE: This is a dose-escalation study. Patients in phase II are stratified according to use of enzyme-inducing antiepileptic drugs (EIAEDs) (yes vs no) and disease type (glioblastoma multiforme with stable neuro-imaging after radiotherapy vs recurrent malignant glioma). Patients in phase I must be currently receiving EIAEDs.

* Phase I: Patients receive CCI-779 IV over 30 minutes once weekly. Treatment repeats every 4 weeks in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of CCI-779 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.

* Phase II: Patients receive CCI-779 as in Phase I. Patients who are candidates for surgical resection of recurrent disease receive CCI-779 IV over 30 minutes 2 hours prior to surgery and then once weekly, as above, once recovered from surgery.

Patients are followed for survival.

PROJECTED ACCRUAL: A total of 36 patients will be accrued for phase I of this study within 12 months. A total of 87 patients will be accrued for phase II of this study within 12 months.

Eligibility Criteria:
DISEASE CHARACTERISTICS:

* Histologically confirmed intracranial malignant glioma

  * Glioblastoma multiforme
  * Anaplastic astrocytoma
  * Anaplastic oligodendroglioma
  * Anaplastic mixed oligoastrocytoma
  * Malignant astrocytoma not otherwise specified
* Initial diagnosis of low-grade allowed, if subsequently progressed
* Recurrent disease must have documented progression by MRI or CT scan
* Progressive disease must have failed prior radiotherapy
* Recent resection of recurrent or progressive tumor allowed provided all of the following are met:

  * Recovered from surgery
  * CT scan or MRI performed no more than 96 hours postoperatively OR at 4-6 weeks postoperatively
  * Concurrent steroid dosage must be stable
* Confirmation of true progressive disease (by PET, thallium scan, MR spectroscopy, or surgical documentation) required after prior interstitial brachytherapy or stereotactic radiosurgery

PATIENT CHARACTERISTICS:

Age:

* 18 and over

Performance status:

* Karnofsky 60-100%

Life expectancy:

* More than 8 weeks

Hematopoietic:

* WBC at least 3,000/mm3
* Absolute neutrophil count at least 2,000/mm3
* Platelet count at least 120,000/mm3
* Hemoglobin at least 10 g/dL (transfusion allowed)

Hepatic:

* Bilirubin less than 1.5 times upper limit of normal (ULN)
* SGOT less than 1.5 times ULN
* Cholesterol less than 350 mg/dL
* Triglycerides less than 400 mg/dL

Renal:

* Creatinine less than 1.5 mg/dL
* Creatinine clearance at least 60 mL/min

Other:

* No active infection
* No other malignancy within the past 3 years except nonmelanoma skin cancer or carcinoma in situ of the cervix
* No significant medical illness that would preclude study
* No disease that would obscure toxicity or dangerously alter drug metabolism
* No history of allergic reactions attributed to compounds of similar chemical or biologic composition to CCI-779 or allergy to or inability to receive antihistamines
* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception during and for 12 weeks after study

PRIOR CONCURRENT THERAPY:

Biologic therapy:

* At least 1 week since prior interferon

Chemotherapy:

* At least 2 weeks since prior vincristine
* At least 3 weeks since prior procarbazine
* At least 6 weeks since prior nitrosoureas
* Phase I:

  * 2 prior chemotherapy regimens allowed
  * 1 prior adjuvant regimen and 1 prior regimen for recurrent or progressive disease OR
  * 2 prior regimens for progressive tumor
* Phase II:

  * No more than 1 prior chemotherapy regimen for recurrent malignant glioma
  * No prior chemotherapy allowed for stable glioblastoma multiforme

Endocrine therapy:

* See Disease Characteristics
* At least 1 week since prior tamoxifen

Radiotherapy:

* See Disease Characteristics
* At least 4 weeks since prior radiotherapy for progressive disease
* No more than 1 month since prior radiotherapy for nonprogressive glioblastoma multiforme

Surgery:

* See Disease Characteristics

Other:

* Recovered from prior therapy
* At least 1 week since prior noncytotoxic agents