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

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.

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