Everolimus and Imatinib Mesylate in Treating Patients With Metastatic or Unresectable Kidney Cancer

Study Overview
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Brief Summary
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RATIONALE: Everolimus and imatinib mesylate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Everolimus may also block blood flow to the tumor. Giving everolimus together with imatinib mesylate may kill more tumor cells. PURPOSE: This phase II trial is studying how well giving everolimus together with imatinib mesylate works in treating patients with metastatic or unresectable kidney cancer.

Detailed Description
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OBJECTIVES: Primary Estimate the proportion of patients with previously treated metastatic or unresectable clear cell carcinoma of the kidney who are progression free (complete response [CR], partial response [PR], or stable disease [SD]) at 3 months after treatment with everolimus and imatinib mesylate. Secondary Estimate median time to progression in patients treated with this regimen. Determine the proportion of patients whose best overall response are CR, PR, SD, or progressive disease. Evaluate the mean and range of the maximum percent reduction in tumor size. Describe the toxicities of this regimen in these patients. OUTLINE: This is an open-label, multicenter study. Patients receive oral imatinib mesylate and oral everolimus once daily beginning on day 1 and continuing in the absence of disease progression. PROJECTED ACCRUAL: A total of 43 patients will be accrued for this study.

Official Title
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A Phase II Study of the Mammalian Target of Rapamycin (mTOR) Inhibitor RAD001 in Combination With Imatinib Mesylate in Patients With Previously Treated Advanced Renal Carcinoma

Conditions
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Kidney Cancer

Intervention / Treatment
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* Drug: Everolimus
* Drug: imatinib mesylate


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed clear cell kidney cancer, meeting 1 of the following criteria: Measurable metastatic disease Locally unresectable disease No history of known brain metastases that have not been adequately treated with radiotherapy and/or surgery Must have received ≥ 1 prior systemic therapy for metastatic or unresectable renal cell carcinoma PATIENT CHARACTERISTICS: Eastern Cooperative Oncology Group (ECOG) performance status 0-2 Absolute neutrophil count > 1,500/mm³ Platelet count > 100,000/mm³ Hemoglobin > 8 g/dL Bilirubin < 1.5 times upper limit of normal (ULN) Serum glutamic oxaloacetic transaminase(SGOT) and Serum glutamic pyruvic transaminase(SGPT) < 2.5 times ULN Creatinine < 1.5 times ULN No New York Heat Association grade III-IV cardiac disease No other malignancy within the past 5 years except basal cell skin cancer, cervical carcinoma in situ, or insignificant or inactive disease No chronic liver disease (i.e., chronic active hepatitis or cirrhosis) No severe or uncontrolled medical disease No gastrointestinal disease or impairment that would hinder the absorption of everolimus No uncontrolled diabetes No chronic renal disease No active uncontrolled infection No congestive heart failure No myocardial infarction within the past 6 months PRIOR CONCURRENT THERAPY: See Disease Characteristics More than 2 weeks since prior major surgery More than 4 weeks since prior chemotherapy (6 weeks for nitrosourea or mitomycin C) More than 4 weeks since prior immunotherapy More than 4 weeks since other prior investigational agents No prior radiotherapy to > 25% of bone marrow No prior treatment with an mammalian target of rapamycin(mTOR) inhibitor No concurrent therapeutic warfarin

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 100 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: Everolimus and Imatinib Mesylate<br>Everolimus: 2.5 mg daily by mouth Imatinib Mesylate: 600 mg daily by mouth | Drug: Everolimus<br>* 2.5 mg by mouth daily<br>* Other names: Certican;Drug: imatinib mesylate<br>* 600 mg by mouth daily<br>* Other names: STI-571;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free Survival at 3 Months |  | 3 months post 1st dose | 
| Overall Number of Participants Who Achieve a Response Rate (Complete Response, Partial Response, and Stable Disease) at 3 Months |  | Up to 4 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Median Time to Progression |  | Time to progression | 
| Number of Subjects That Demonstrated a Reduction in Tumor Measurements. | Number of subjects that received at least one post-baseline scan that demonstrated a reduction in sum target lesions per Response Evaluation Criteria in Solid Tumors (RECIST) criteria. | Up to 4 years | 
| Number of Participants With Adverse Events | Toxicity assessments will be obtained as follows: Cycle 1: Weeks 1,2,3 Cycle 2: Weeks 6,9 Cycle 3: Weeks 12, 15 Cycle 4: Weeks 18, 21 Cycle 5: Weeks 24, 27 Cycle 6+: Every visit during these cycles Safety assessments will consist of evaluating adverse events and serious adverse events. | Duration of study, Up to 4 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stage III renal cell cancer, stage IV renal cell cancer, clear cell renal cell carcinoma, recurrent renal cell cancer