Sorafenib and RAD001 Renal Cell Carcinoma

Inclusion Criteria:

Histologically- or cytologically-confirmed renal cell carcinoma containing predominant (>50%) clear cell histology, which is metastatic or unresectable
Cytoreductive nephrectomy is allowed
Evidence of RECIST-defined measurable disease (lesions that can be accurately measured in at least one dimension with the longest diameter ≥ 20mm using conventional techniques or ≥10 mm with spiral CT scan)
Male or female at least 21 years old
ECOG performance status 0-1

Adequate bone marrow function:

ANC ≥ 1500/uL
platelet count ≥ 100,000/uL
hemoglobin ≥ 9.0 g/dL

Adequate hepatic function:

Total bilirubin ≤ 1.5 X ULN
AST (SGOT) ≤ 2.5 X ULN
ALT (SGPT) ≤ 2.5 X ULN

Adequate renal function as determined by either:

Calculated or measured creatinine clearance ≥ 40 mL/min (for calculated creatinine clearance, Cockroft-Gault equation will be used) Modified Cockcroft-Gault formula: ((140 - age(yrs)) x (actual weight(kg))) / (72 x serum creatinine(mg/dl))

* Multiply by another factor of 0.85 if female

Serum creatinine ≤ 1.5 X ULN
Able to swallow oral medications
Resolution of any pre-existing toxicity from prior therapy to NCI CTCAE V3.0 ≤ grade 1
Signed and dated informed consent document
Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures
More than 28 days since any prior therapy, including investigational agents and surgical procedures

Exclusion Criteria:

Collecting duct, papillary, or chromophobe type renal cell carcinoma without a clear cell component are excluded. Transitional cell carcinoma of the renal pelvis is excluded
No more than two prior systemic regimens for renal cell carcinoma
Phase I: No prior treatment with sorafenib. Phase II: No prior treatment with prior anti-VEGF therapies, including sorafenib, sunitinib, thalidomide, or bevacizumab
No prior treatment with RAD001, CCI-779, or similar agents
Prior surgery, radiation therapy, or systemic therapy for renal cell carcinoma within 4 weeks of starting study treatment
History of or known brain metastasis, spinal cord compression, or carcinomatous meningitis, or new evidence of brain or leptomeningeal disease on screening CT or MRI scan
Any of the following within 12 months prior to study drug administration: myocardial infarction, unstable or severe angina, coronary or peripheral artery bypass graft, NYHA functional Class II, III, IV congestive heart failure, cerebrovascular accident or transient ischemic attack, or pulmonary embolism
Hypertension that is unable to be controlled with medications
Known human immunodeficiency virus (HIV) or acquired immune deficiency syndrome (AIDS)-related illness
"Currently active" second malignancy other than non-melanoma skin cancers. Patients are not considered to have a "currently active" malignancy if they have completed therapy and are considered to have a less than 30% risk of relapse
Current treatment on another clinical trial
Pregnant or breastfeeding
Chronic treatment with systemic steroids or other immunosuppressive agent
Patients with an active bleeding diathesis or on oral vitamin K antagonist medication (except low dose warfarin)
History of malabsorption syndrome, disease significantly affecting gastrointestinal function or major resection of stomach or small bowel that could interfere with absorption, distribution, metabolism, or excretion of study drugs
Any serious and/or unstable pre-existing medical, psychiatric, or other condition (including lab abnormalities) that could interfere with subject safety or obtaining informed consent. Examples of such include uncontrolled diabetes, nonhealing wound, severe infection, severe malnutrition, ventricular arrhythmias, active ischemic heart disease, chronic liver or renal disease, or active upper GI tract ulceration -