Biomarker Trial of Everolimus in Patients With Advanced Renal Cell Carcinoma

A Phase II Biomarker Trial of Everolimus in Patients With Advanced Renal Cell Carcinoma

The purpose of this study is to determine if certain features of tumor specimens sampled prior to therapy can predict for the likelihood of responding to everolimus.

• Participants will undergo a CT or ultrasound guided biopsy of an accessible tumor lesion before beginning the study medication.
• Everolimus tablets will be taken orally once a day. Participants will undergo a physical exam and will be asked questions about their general health and specific questions about any problems they might be having. Photographs will be taken of the tumor to assess the response to treatment. This will be done by a CT or MRI scan. Blood tests will be performed every 4 weeks. In addition, blood for research purposes will be done on day 1 of every other cycle. A urine test will be done every 4 weeks.

Inclusion Criteria:

• Patients must have at least one site of disease which in the opinion of the investigator is safely accessible by CT guided biopsy or metastasectomy. Safely accessible metastatic disease will be defined to include those lesions which are palpable with no overlying viscera and are at least 2cm in size. Given the paucity of subcutaneous lesions in RCC, lesions which are felt to be safe to biopsy will also be allowed. These lesions include pleural-based tumors, peripheral liver lesions, kidney lesions and bone lesions with exophytic soft tissue component. As with palpable lesions, these other lesions should be at least 2cm in size with no overlying viscera.
• At least one measurable site of disease, other than the biopsy site, according to RECIST criterial that has not been previously irradiated. Th the patient has had previous radiation to the marker lesion(s), there must be evidence of progression since the radiation
• Metastatic renal carcinoma with histologic confirmation by the treating center of either primary or a metastatic lesion. Non-clear cell histologies will be allowed
• 18 years of age or older
• Minimum of four weeks since any major surgery, completion of radiation, or completion of all prior systemic anticancer therapy (adequately recovered from the acute toxicities of any prior therapy)
• ECOG Performance status of 1 or less
• Adequate bone marrow, liver and renal function as outlined in the protocol
• Fasting serum cholesterol < 300mg/dL OR < 7.75 mmol/L AND fasting triglycerides < 2.5 x ULN
• Life expectancy of greater than 6 months

Exclusion Criteria:

• Prior treatment with any investigation drug within the preceding 4 weeks
• Chronic treatment with systemic steroids or another immunosuppressive agent
• Patients should not receive immunization with attenuated live vaccines within one week of study entry or during study period
• Uncontrolled brain or leptomeningeal metastases, including patients who continue to require glucocorticoids for brain or leptomeningeal metastases. Treated brain metastases will be allowed. Treated brain metastases are defined as having no evidence of progression or hemorrhage after treatment and no ongoing requirement for dexamethasone, as ascertained by clinical examination and brain imaging (MRI or CT) during the screening period. Anticonvulsants (stable dose) are allowed. Treatment for brain metastases may include whole brain radiotherapy (WBRT), radiosurgery (RS: Gamma Knife, LINAC or equivalent) or a combination as deemed appropriate by the treating physician. Patients with CNS metastases treated by neurosurgical resection performed within 3 months prio to day 1 will be excluded.
• Other malignancies within the past 3 years except for adequately treated carcinoma of the cervix or basal or squamous cell carcinomas of the skin
• Patients who have any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study
• Uncontrolled diabetes mellitus as defined by a fasting serum > 1.5 x ULN
• A known history of HIV seropositivity.
• Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of everolimus
• Patients with active, bleeding diathesis or on systemic anticoagulation. Aspirin is permitted.
• Women who are pregnant or breast feeding, or women/men able to conceive and unwilling to practice an effective method of birth control.
• Patients who have received prior treatment with an mTOR inhibitor.
• Patients with known hypersensitivity to everolimus or other rapamycins or to its excipients.
• History of noncompliance to medical regimens