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

• Progression-free Survival at 3 Months [ Time Frame: 3 months post 1st dose ] [ Designated as safety issue: No ]
• Overall Number of Participants Who Achieve a Response Rate (Complete Response, Partial Response, and Stable Disease) at 3 Months [ Time Frame: Up to 4 years ] [ Designated as safety issue: No ]

• Median Time to Progression [ Time Frame: Time to progression ] [ Designated as safety issue: No ]
• Maximum Percent Reduction of Tumor Measurement [ Time Frame: Up to 4 years ] [ Designated as safety issue: No ]
• Number of Participants With Adverse Events [ Time Frame: Duration of study, Up to 4 years ] [ Designated as safety issue: Yes ]

  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.

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.

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.

• Drug: Everolimus
  205 mg by mouth daily
  Other Names:

  • Afinitor
  • RAD001
  • Certican
• Drug: imatinib mesylate
  600 mg by mouth daily
  Other Names:

  • Gleevec
  • STI-571

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