Pazopanib in Previously Treated Patients With Metastatic Renal Cell Carcinoma

Inclusion Criteria

• All patients must have histologically documented metastatic or unresectable locally recurrent clear cell renal carcinoma. In patients with mixed histologies, any percentage of clear cell histology is acceptable.
• Patients must have had only one previous targeted agent therapy with either sunitinib or bevacizumab. Patients must have progressed either during or within 3 months of discontinuing treatment with one of these agents. Patients who stopped either sunitinib or bevacizumab because of unacceptable toxicity are also eligible.
• Patients may have received one previous regimen containing traditional immunotherapy (interferon, interleukin-2), chemotherapy, or combination chemoimmunotherapy for metastatic disease.
• Previous nephrectomy is required unless clinically contraindicated (e.g. extensive liver or bone metastases; primary tumor 20 mm with conventional techniques, or as >10 mm with spiral computerized tomography (CT) scan according to the Response Evaluation Criteria in Solid Tumors (RECIST).
• Absolute neutrophil count (ANC) >1500; platelets >75,000 (within 7 days prior to study treatment).
• Adequate liver function as measured by serum bilirubin 2 months prior to study enrollment. Routine screening with CNS imaging studies (computed tomography [CT] or magnetic resonance imaging [MRI]) is required only if clinically indicated, or if the patient has a history of CNS metastases.
• Malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel.
• Active peptic ulcer disease, inflammatory bowel disease, or other gastrointestinal condition increasing the risk of perforation.
• History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 4 weeks prior to beginning therapy.
• Presence of uncontrolled infection.
• Concurrent cancer therapy (e.g., chemotherapy, radiation therapy, surgery, immunotherapy, biologic therapy, hormonal therapy, or tumor embolization).
• Concurrent treatment with an investigational agent or participation in another clinical trial.
• Use of an investigational anti-cancer drug within 30 days or 5 half-lives, whichever is longer, preceding the first dose of pazopanib.
• Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to pazopanib.
• Has taken or is taking prohibited medications.
• Corrected QT interval (QTc) prolongation defined as QTc interval >470 msec.
• History of any one of the following cardiac conditions within the past 6 months:
• Cardiac angioplasty or stenting
• Myocardial infarction
• Unstable angina
• History of cerebrovascular accident within the past 6 months
• Poorly controlled hypertension (systolic blood pressure [SBP] of >140 mmHg, or diastolic blood pressure [DBP] of >90 mmHg).

Note: Initiation or adjustment of antihypertensive medication(s) is permitted prior to study entry. The blood pressure (BP) must be re- assessed on two occasions that are separated by a minimum of 24 hours. The mean SBP-DBP values from both BP assessments must be <140/90 mmHg in order for a patient to be eligible for the study.

• Presence of any non-healing wound, fracture, or ulcer, or the presence of symptomatic peripheral vascular disease.
• Evidence of bleeding diathesis or coagulopathy.
• Major surgical procedure, open biopsy, or significant traumatic injury within 4 weeks prior to beginning therapy, or anticipation of the need for a major surgical procedure during the course of the study. Minor surgical procedures such as fine needle aspiration or core biopsy within 1 week prior to beginning therapy are also excluded.
• Pregnant or lactating female. All patients of childbearing potential must agree to use adequate contraception for 2 weeks prior to beginning pazopanib, during the entire study, and for 60 days after pazopanib is discontinued.
• Class III or IV heart failure as defined by the New York Hea