CCI-779 and EKB-569 in Treating Patients With Advanced Solid Tumors

Study Overview
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Brief Summary
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This phase I trial is studying the side effects, best way to give, and best dose of CCI-779 and EKB-569 in treating patients with advanced solid tumors. Drugs used in chemotherapy, such as CCI-779, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. EKB-569 may stop the growth of tumor cells by blocking some of the enzymes needed for their growth. Giving CCI-779 together with EKB-569 may kill more tumor cells.

Detailed Description
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OBJECTIVES: I. Determine the maximum tolerated dose of the combination of CCI-779 and EKB-569 in patients with advanced solid tumors. II. Determine the toxicity of this regimen in these patients. III. Determine the response rate in patients treated with this regimen. OUTLINE: This is a dose-escalation study. Patients are assigned to 1 of 3 treatment groups. Group I: Patients receive oral EKB-569 on days 1-28 and oral CCI-779 on days 1-7 and 15-21. Cohorts of 3-6 patients receive escalating doses of EKB-569 and 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. Group II: Patients receive oral EKB-569 at the MTD on days 4-28 of course 1 and days 1-28 of all subsequent courses and CCI-779 at the MTD on days 1-3 and 15-17. Group III: Patients receive EKB-569 at the MTD as in group I and oral CCI-779 at the MTD on days 7-9 and 19-21 of course 1 and days 1-3 and 15-17 of all subsequent courses. In all groups, courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. PROJECTED ACCRUAL: A total of 30-42 patients (18-30 for group I, 6 for group II, and 6 for group III) will be accrued for this study within 1.35-1.75 years.

Official Title
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A Phase 1 Trial of CCI-779 in Combination With EKB-569, an EGFR Inhibitor, in Patients With Solid Tumors

Conditions
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Unspecified Adult Solid Tumor, Protocol Specific

Intervention / Treatment
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* Drug: pelitinib
* Drug: temsirolimus


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed unresectable solid tumor for which there is no known standard therapy that is potentially curative or capable of extending life expectancy No CNS metastases Performance status - ECOG 0-2 At least 12 weeks Absolute neutrophil count ≥ 1,500/mm^3 Platelet count ≥ 100,000/mm^3 Hemoglobin ≥ 10 g/dL Bilirubin normal AST ≤ 3 times upper limit of normal (ULN) (5 times ULN if liver involvement) Creatinine ≤ 1.5 times ULN No New York Heart Association class III or IV heart disease Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception during and for 3 months after study participation Fasting cholesterol < 350 mg/dL Fasting triglycerides < 400 mg/dL No uncontrolled infection No seizure disorder More than 4 weeks since prior immunotherapy More than 4 weeks since prior biologic therapy No concurrent immunotherapy No concurrent prophylactic colony-stimulating factor therapy More than 4 weeks since prior chemotherapy (6 weeks for mitomycin or nitrosoureas) and recovered No other concurrent chemotherapy No concurrent oral contraceptives More than 4 weeks since prior radiotherapy No prior radiotherapy to > 30% of bone marrow No concurrent radiotherapy More than 7 days since prior CYP3A4 inducers No prior mTOR-targeting agents No prior epidermal growth factor receptor-targeting agents No concurrent antiretroviral therapy that induces or inhibits CYP3A4 for HIV-positive patients No other concurrent investigational agents No concurrent warfarin

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

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm I<br>Patients receive oral EKB-569 on days 1-28 and oral CCI-779 on days 1-7 and 15-21. | Drug: pelitinib<br> <br> * Other names: EKB-569;Drug: temsirolimus<br>* Given PO<br>* Other names: Torisel;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum tolerated dose (MTD) defined as the dose level below the lowest dose that induces dose-limiting toxicity in at least one-third of patients |  | Up to 28 days | 
| Number and severity of all adverse events per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v3.0 | Frequency distributions, graphical techniques and other descriptive measures will form the basis of these analyses. | Up to 30 days after last dose of study treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Best response according to the Response Evaluation Criteria in Solid Tumors (RECIST) |  | Time from the start of the treatment until disease progression/recurrence, assessed up to 3 years | 
| Time until any treatment related toxicity |  | Up to 3 years | 
| Time until treatment related grade 3+ toxicity |  | Up to 3 years | 
| Time until hematologic nadirs (white blood cells [WBC], absolute neutrophil count [ANC], platelets) |  | Up to 3 years | 
| Time to progression |  | Up to 3 years | 
| Time to treatment failure |  | Time from registration to documentation of progression, unacceptable toxicity, or refusal to continue participation by the patient, assessed up to 3 years |