CCI-779 in Treating Patients With Malignant Glioma

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Phase I/II Trial Of CCI-779 In Patients With Malignant Glioma

Conditions
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Brain and Central Nervous System Tumors

Intervention / Treatment
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* Drug: temsirolimus


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 120 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: temsirolimus|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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recurrent adult brain tumor, adult glioblastoma, adult anaplastic astrocytoma, adult anaplastic oligodendroglioma, adult mixed glioma, adult giant cell glioblastoma, adult gliosarcoma