Everolimus (RAD001) For Advanced Renal Cell Carcinoma (RCC) Before Kidney Removal

Neoadjuvant Everolimus (RAD001)for Advanced RCC Before Cytoreductive Nephrectomy, With Correlative Tumor Studies (Protocol #: 06-08-20-01)

The purpose of this multicenter, pilot, open-label, Phase II clinical trial is to discover if Everolimus(RAD001) is safe and effective in people who have advanced kidney cancer (renal cell carcinoma - RCC).

Since 2002, Everolimus has been studied in more than 2500 patients with various types of cancer as a single agent (a drug that is used alone to treat the cancer) or in combination with a number of well known anticancer therapies. Various studies, in animals such as in mice with cancer and in humans with cancer have shown that Everolimus can slow the growth of cancer.

Everolimus will be taken in pill form by mouth daily for 3-5 weeks followed by surgery to remove the effected kidney. After 2-4 weeks following the surgery, Everolimus will be resumed at the same dose.

Everolimus has significantly improved outcomes following prior therapy. This study is a biomarker driven Phase II trial that will assess the activity of everolimus as first-line therapy for renal cell carcinoma. Following initial kidney tumor biopsy, everolimus is administered for 3-5 weeks before cytoreductive nephrectomy and everolimus is then resumed and continued until tumor progression or intolerable toxicities. Any correlation of tumor tissue biomarker changes from initial biopsy to nephrectomy specimen with long-term progression-free survival will be determined. This trial may enable the identification of factors predictive of significant benefit from everolimus administered as first-line therapy by employing the neoadjuvant therapy paradigm.

Inclusion Criteria:

• Advanced (metastatic) RCC
• Histology: clear cell, papillary or chromophobe
• 3 out 6 risk factors (by Memorial Sloan Kettering Cancer Center criteria and one additional criterion: multiple sites of metastasis) or not candidates for or refuse sunitinib.
• Must have at least one measurable metastatic site according to Response Evaluation Criteria In Solid Tumors (RECIST) criteria that has not been previously irradiated.
• Must be deemed surgical candidates for cytoreductive nephrectomy by the urologist.
• Age 18 years of age or older
• Eastern Cooperative Oncology Group (EGOG) PS 0-2
• Adequate bone marrow function
• Adequate liver function as shown by:
• Adequate renal function
• Fasting serum cholesterol AND fasting triglycerides within normal limits
• Signed informed consent

Exclusion Criteria:

• Collecting duct, medullary histologies or sarcomatoid differentiation.
• Central Nervous System (CNS) or leptomeningeal metastases.
• Inappropriate candidates for cytoreductive nephrectomy or who have any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study
• severely impaired lung function
• uncontrolled diabetes
• active (acute or chronic) or uncontrolled severe infections
• liver disease such as cirrhosis, chronic active hepatitis or chronic persistent hepatitis
• Ineligible for cytoreductive nephrectomy
• Current or prior systemic anticancer therapies (including chemotherapy, antibody based therapy, or investigational drugs)
• Other malignancies within the past 3 years except for localized carcinoma of the cervix, basal or squamous cell carcinomas of the skin, or localized prostate cancer with Gleason Score less than 7 treated with radiation or surgery and no evidence of progression.
• Major surgery (defined as requiring general anesthesia) or significant traumatic injury within 4 weeks of start of enrollment
• Anticipated major surgery (other than CN) during the course of the study
• A known history of HIV seropositivity
• Hepatitis C seropositivity
• Chronic, systemic treatment with corticosteroids or another immunosuppressive agent. Topical or inhaled corticosteroids are allowed.
• Immunization with attenuated live vaccines within one week of study entry or during study period
• Known hypersensitivity to RAD001 (everolimus) or other rapamycins or to its excipients
• Impairment of gastrointestinal function or gastrointestinal disease
• Active, bleeding diathesis
• Female patients who are pregnant or breast feeding, or adults of reproductive potential who are not using effective birth control methods.
• History of noncompliance to medical regimens
• Unwilling to or unable to comply with the protocol including mandated biopsies