Pazopanib Versus Sunitinib in the Treatment of Locally Advanced and/or Metastatic Renal Cell Carcinoma (COMPARZ)

• Overall Survival [ Time Frame: Randomization until death ] [ Designated as safety issue: No ]
• Objective Response Rate [ Time Frame: Randomization until time of confirmed best response ] [ Designated as safety issue: No ]
• Time to Response [ Time Frame: Randomization until time of first documented response (partial or complete response) ] [ Designated as safety issue: No ]
• Duration of Response [ Time Frame: Time from first documented partial or complete response until disease progression or death ] [ Designated as safety issue: No ]
• Safety [ Time Frame: From time of first dose of study drug to approximately one month after discontinuation of study drug ] [ Designated as safety issue: No ]
• Health Outcomes Analysis [ Time Frame: From randomization until discontinuation of study drug ] [ Designated as safety issue: No ]

This study is being conducted to provide a direct comparison of the efficacy, safety and tolerability for pazopanib and sunitinib (SUTENT)

This study will evaluate the efficacy and safety of pazopanib compared to sunitinib in subjects with advanced RCC who have received no prior systemic therapy for advanced or metastatic RCC. Subjects will be randomized in a 1:1 ratio to receive either 800mg pazopanib to be administered once daily orally continuous dosing or 50mg sunitinib to be administered in 6-week cycles: 50mg orally daily for 4 weeks followed by 2 weeks off treatment. Subjects are permitted to receive supportive care throughout the study including transfusion of blood and blood products, treatment with antibiotics, anti-emetics, anti-diarrheal agents, analgesics, erythropoietin, or bisphosphonates, when appropriate. The study treatment will continue until subjects experience disease progression, unacceptable toxicity, withdraw consent, or death.

• Drug: Pazopanib
  800 mg administered once daily orally continuous dosing
• Drug: Sunitinib
  50 mg sunitinib to be administered in 6-week cycles: 50mg orally daily for 4 weeks followed by 2 weeks off treatment

• Active Comparator: Sunitinib
  Control arm
  Intervention: Drug: Sunitinib
• Experimental: Pazopanib
  Experimental arm
  Intervention: Drug: Pazopanib

Inclusion Criteria:

• Written informed consent
• Diagnosis of renal cell carcinoma with clear-cell component histology.
• Received no prior systemic therapy (interleukin-2, interferon-alpha, chemotherapy, bevacizumab, mTOR inhibitor, sunitinib, sorafenib or other VEGF TKI) for advanced or metastatic RCC
• Locally advanced or metastatic renal cell carcinoma
• Measurable disease by CT or MRI
• Karnofsky performance scale status of >=70
• Age >=18 years
• A female is eligible to enter and participate in this study if she is of: non-childbearing or agrees to use adequate contraception.
• Adequate organ system function
• Total serum calcium concentration <12.0mg/dL
• Left ventricular ejection fraction >= lower limit of institutional normal.

Exclusion Criteria:

• Pregnant or lactating female (unless agrees to refrain from nursing throughout the treatment period and for 14 days following the last dose of study)
• History of another malignancy (unless have been disease-free for 3 years)
• History or clinical evidence of central nervous system (CNS) metastases (unless have previously-treated CNS metastases and meet all 3 of the following criteria are: are asymptomatic, have had no evidence of active CNS metastases for >=6 months prior to enrolment, and have no requirement for steroids or enzyme-inducing anticonvulsants)
• Clinically significant gastrointestinal abnormalities including, but not limited to: malabsorption syndrome, major resection of the stomach or small bowel that could affect the absorption of study drug, active peptic ulcer disease, known intraluminal metastatic lesion/s with suspected bleeding, Inflammatory bowel disease, ulcerative colitis, or other gastrointestinal conditions with increased risk of perforation, history of abdominal fistula, gastrointestinal perforation, or intra abdominal abscess within 28 days prior to beginning study treatment.
• Presence of uncontrolled infection.
• Prolongation of corrected QT interval (QTc) > 480 milliseconds
• History of any one or more of the following cardiovascular conditions within the past 12 months: cardiac angioplasty or stenting, myocardial infarction, unstable angina, coronary artery by-pass graft surgery, symptomatic peripheral vascular disease, Class III or IV congestive heart failure, as defined by the New York Heart Association
• History of cerebrovascular accident including transient ischemic attack within the past 12 months
• History of pulmonary embolism or untreated deep venous thrombosis (DVT) within the past 6 months (unless had recent DVT and have been treated with therapeutic anti-coagulating agents for at least 6 weeks)
• Poorly controlled hypertension (defined as systolic blood pressure of >=150mmHg or diastolic blood pressure of >=90mmHg). Initiation or adjustment of antihypertensive medication(s) is permitted prior to study entry
• Prior major surgery or trauma within 28 days prior to first dose of study drug and/or presence of any non-healing wound, fracture, or ulcer.
• Evidence of active bleeding or bleeding susceptibility
• Spitting/coughing up blood within 6 weeks of first dose of study drug
• Known endobronchial lesions and/or lesions infiltrating major pulmonary vessels
• Any serious and/or unstable pre-existing medical, psychiatric, or other conditions that could interfere with patient's safety, obtaining informed consent or compliance to the study.
• Use any prohibited medications within 14 days of the first dose of study medication.
• Use of an investigational agent, including an investigational anti-cancer agent, within 28 days or 5 half-lives, whichever is longer, prior to the first dose of study drug.
• Prior use of an investigational or licensed drug that targets VEGF or VEGF receptors (eg. bevacizumab, sunitinib, sorafenib, etc), or are mTOR inhibitors (eg. temsirolimus, everolimus, etc).
• Is now undergoing and/or has undergone in the 14 days immediately prior to first dose of study drug, any cancer therapy (surgery, tumor embolization, chemotherapy, radiation therapy, immunotherapy, biological therapy, or hormonal therapy)
• Any ongoing toxicity from prior anti-cancer therapy that is >Grade 1 and/or that is progressing in severity.
• Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to pazopanib or sunitinib.