Pazopanib Versus Temsirolimus in Poor-Risk Clear-Cell Renal Cell Carcinoma (RCC)

Inclusion Criteria

• Pathologic confirmation of metastatic or locally advanced RCC with a major clear cell component.
• Measurable disease by RECIST criteria.
• Age >/= 18 years
• ECOG performance status 0-2 or Karnofsky Performance Status >/= 60%
• Meets criteria for poor-risk defined as 3 or more of the following: ECOG performance status 2, anemia (hemoglobin lower than reference range), elevated serum LDH > 1.5x upper limit of normal (ULN), hypercalcemia (corrected serum calcium level > upper limit of normal), time from initial RCC diagnosis to registration on this trial 1 metastatic organ sites.
• Adequate organ and marrow function within 14 days of registration as defined below: a) Absolute neutrophil count >/=1,500/µL b) Platelets >/=100,000/µL c) Hgb >/= 9.0 g/dL (transfusion allowed) d) Renal: serum creatinine /= 40 cc/min and random urine protein:creatinine ratio (UPC) 2 weeks (14 days) at time of randomization.
• Female patients of childbearing potential (not postmenopausal for at least 12 months and not surgically sterile) must have a negative serum or urine pregnancy test within 14 days of study registration. Pregnancy test must be repeated if performed > 14 days before starting study drug.

Exclusion Criteria

• Prior malignancy, except for non-melanoma skin cancer, in situ carcinoma of any site, or other cancers for which the patient has been adequately treated and disease free for 2 years
• Prior targeted therapy (anti-VEGF agents or mTOR inhibitors) including adjuvant therapy, and prior chemotherapy for mRCC. However, prior immunotherapy (cytokines or vaccines) is allowed.
• Any experimental drug while on this study; however, concomitant bone targeted therapy (bisphosphonates or the anti-RANK ligand denosumab) is allowed.
• Uncontrolled brain metastases and infections. Patients with brain metastases treated with Gamma Knife (GK) or whole brain radiation within 24 hours of registration.
• History of stroke within 6 months of registration
• Clinically significant cardiovascular disease, defined as myocardial infarction (or unstable angina) within 6 months of registration, New York Heart Association (NYHA) Grade II or greater congestive heart failure, serious cardiac dysrhythmia refractory to medical management. However, treated and controlled or stable/not clinically significant cardiovascular disease is allowed per evaluation by cardiologist.
• Uncontrolled hypertension (home blood pressure readings are permitted) or prior history of hypertensive crisis or hypertensive encephalopathy; however, treatment of hypertension with medications is permitted.
• History of uncontrolled hemoptysis (>/= 1/2 teaspoon of bright red blood per episode) within 1 month prior to Day 1
• Significant vascular disease including aortic aneurysm, aortic dissection.
• Symptomatic peripheral vascular disease
• Pregnancy
• HIV-positive patients receiving combination anti-retroviral therapy
• Coagulopathy or bleeding diathesis
• Concomitant treatment with rifampin, St. John's wort, or the cytochrome p450 enzyme-inducing antiepileptic drugs (phenytoin, carbamazepine or Phenobarbital)
• Major surgery within 28 days prior to registration
• Core biopsy or other minor surgical procedure, excluding placement of a vascular access device within 7 days prior to starting drug
• History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to study registration
• Serious non-healing wound
• Baseline QTcB >/= 470 msec.