Clinical Trial Finder

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

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.#46;no) and disease type (glioblastoma multiforme with stable neuro-imaging after radiotherapy vs.#46;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.