CCI-779 in Treating Patients With Advanced Solid Tumors

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 trial to study the effectiveness of CCI-779 in treating patients who have advanced solid tumors.

Detailed Description
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OBJECTIVES: Determine the safety, tolerability, and maximum tolerated dose (MTD) of CCI-779 in patients with advanced solid tumors (part I) who are not receiving anticonvulsant therapy. Determine the safety, tolerability, and MTD in patients with recurrent gliomas or brain metastases (part II) who are receiving anticonvulsant therapy. Determine the preliminary pharmacokinetic profile and antitumor activity of CCI-779 in these patients. OUTLINE: This is an open-label, dose-escalation study. Part I: Patients receive CCI-779 IV over 30 minutes on days 1-5, followed by a 9 day rest period. Treatment courses repeat every 2 weeks in the absence of disease progression or unacceptable toxicity. The maximum tolerated dose for part I is defined as the dose level at which 33% of patients experience dose limiting toxicity. Part II: Patients receive the same treatment schedule as part I. Three patients with CNS tumors are entered at the dose of CCI-779 determined to be the MTD in Part I. At least 3 patients are entered at each dose level in part II. PROJECTED ACCRUAL: Approximately 20 patients will be accrued for part I for this study within 8 months, and 12 patients will be accrued for part II within 7 months.

Official Title
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A Phase I Study of the Safety, Tolerability, and Pharmacokinetics of Intravenous CCI-779 Given Once Daily for 5 Days Every 2 Weeks to Patients With Advanced Solid Tumors

Conditions
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Brain and Central Nervous System Tumors, Metastatic Cancer, Unspecified Adult Solid Tumor, Protocol Specific

Intervention / Treatment
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* Drug: temsirolimus


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Part I: Histologically proven advanced solid tumors that are refractory or for which no curative therapy exists No CNS metastases, peritumoral edema, or symptomatic brain metastases (part I) Measurable or evaluable disease Part II: Histologically proven recurrent gliomas or brain metastases for which no curative therapy exists Receiving anticonvulsants Measurable or evaluable disease PATIENT CHARACTERISTICS: Age: 18 and over Performance status: ECOG 0-2 Life expectancy: At least 3 months Hematopoietic: Absolute neutrophil count at least 1,500/mm^3 Platelet count at least 100,000/mm^3 Hemoglobin at least 9 g/dL Hepatic: Bilirubin less than 1.5 mg/dL AST or ALT less than 3 times upper limit of normal (ULN) (less than 5 times ULN if liver metastases) Renal: Creatinine less than 2 mg/dL Cardiovascular: No unstable angina No myocardial infarction within past 6 months No maintenance therapy for life-threatening arrhythmias Other: Not pregnant or nursing Fertile patients must use effective contraception HIV negative No active infection or other serious concurrent illness Triglycerides no greater than 300 mg/dL Cholesterol no greater than 350 mg/dL No known hypersensitivity to macrolide antibiotics (e.g., clarithromycin, erythromycin, or azithromycin) PRIOR CONCURRENT THERAPY: Biologic therapy: Not specified Chemotherapy: At least 3 weeks since prior chemotherapy (6 weeks since nitrosoureas and mitomycin) No other concurrent chemotherapy Endocrine therapy: Concurrent corticosteroids used to reduce edema in patients with primary or metastatic CNS tumors allowed No concurrent hormonal therapy Radiotherapy: At least 3 weeks since prior radiotherapy No concurrent radiotherapy Surgery: Not specified Other: At least 1 month since prior investigational agents At least 3 weeks since prior immunosuppressive therapy No concurrent anticonvulsant therapy (part I) No concurrent immunosuppressive therapy (e.g., terfenadine, cisapride, astemizole, pimozide) No known agents that inhibit or induce cytochrome p450

Ages Eligible for Study
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Minimum Age: 18 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: temsirolimus|•Part I: Patients receive CCI-779 IV over 30 minutes on days 1-5, followed by a 9 day rest period. Treatment courses repeat every 2 weeks in the absence of disease progression or unacceptable toxicity. The maximum tolerated dose for part I is defined as the dose level at which 33% of patients experience dose limiting toxicity. •Part II: Patients receive the same treatment schedule as part I. Three patients with CNS tumors are entered at the dose of CCI-779 determined to be the MTD in Part I. At least 3 patients are entered at each dose level in part II.|

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, unspecified adult solid tumor, protocol specific, tumors metastatic to brain