Phase II Study of Afinitor vs. Sutent in Patients With Metastatic Non-Clear Cell Renal Cell Carcinoma

Inclusion Criteria

• Histologically confirmed advanced Renal Cell Carcinoma (RCC), with non-clear cell pathology.
• RCC tumor tissue available for correlative sciences, from either primary or metastatic site or both.
• At the time of screening, at least 4 weeks since prior palliative radiation therapy and/or major surgery, and resolution of all toxic effects of prior therapy to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE; version 4.0) Grade 1.
• Subject must have radiographic evidence of metastatic disease with at least 1 measurable per RECIST 1.1 criteria (Attachment 1)].
• Age > 18 years.
• Adequate laboratory values
• Karnofsky Performance Status ≥ 60 (Attachment 2).
• Life expectancy of at least 3 months.
• Written, signed, dated, and witnessed Institutional Review Board (IRB) or Institutional Ethics Committee (IEC) approved informed consent form (ICF) before any screening procedures are performed.

Exclusion Criteria

• Subjects with a history of or active central nervous system (CNS) metastases.
• Prior systemic therapy for RCC, including mTOR and anti-angiogenic therapy, chemotherapy, biologic or experimental therapy.
• Subjects with collecting duct, medullary, small cell, oncocytoma, or lymphoma-type pathology.
• Subjects receiving known strong CYP3A4 isoenzyme inhibitors and/or inducers.
• Major surgery, open biopsy, traumatic injury, or radiotherapy within 4 weeks of the screening visit.
• Subjects who have not recovered from prior biopsy, surgery, traumatic injury, and/or radiation therapy.
• Presence of a non-healing wound or ulcer.
• Grade 3 hemorrhage within the past month.
• Hypertension with systolic blood pressure of >180 mm Hg and/or diastolic pressure >100 mm Hg.
• Subjects with American Heart Association (AHA) Class 2-4 heart disease or any history of congestive heart failure with an ejection fraction 10% despite therapy.
• A history of interstitial pneumonitis.
• Subjects with active autoimmune disorder(s) being treated with immunosuppressive agents within 4 weeks prior to the screening visit.
• Subjects receiving immunosuppressive agents and those with chronic viral/bacterial/fungal illnesses such as human immunodeficiency virus (HIV).
• Patients who have receive immunization with attenuated live vaccines within one week of study entry or during study period.
• Patients with active infection(s), active antimicrobial therapy or serious intercurrent illness.
• History of other prior malignancy in past 5 years.
• Pregnant or nursing women.
• Major medical/psychiatric illness that, in the investigator's judgment, will substantially increase the risk associated with the subject's participation in this study, including inability to absorb oral medications and history of noncompliance to medical regimens.
• Known hypersensitivity to any of the components in everolimus or sunitinib product
• Subjects taking agents that significantly prolong the QTc interval are not eligible.
• Proteinuria with a spot urine protein/creatinine ratio >2 or 24 hour urine protein >2 grams per 24 hours.
• Severely impaired lung function as defined as spirometry and Carbon Monoxide Diffusing Capacity (DLCO) that is 50% of the normal predicted value and/or O2 saturation that is 88% or less at rest on room air.
• Advanced liver disease such as cirrhosis or severe hepatic impairment (Child-Pugh class C).