First Line Pazopanib in Poor Risk Patients With Metastatic Renal Cell Carcinoma

Inclusion Criteria: * Histologically confirmed metastatic or locally advanced (defined as non operable tumor), predominantly clear cell renal cell carcinoma. * At least three of the following five predictors of short survival are required: * Lactate Dehydrogenase (LDH) \> 1.5 x Upper Limit of Normal (ULN) * Hemoglobin \< Lower Limit of Normal (LLN) * corrected serum calcium level \> 10 mg/dl (2.5 mmol/l) * time from initial diagnosis of renal-cell carcinoma to occurrence of metastases of less than 1 year * Karnofsky Status of 60 or 70 * Karnofsky Status ≥ 60 * Age ≥ 18 years or legal age of consent if greater than 18 years * Dated and signed written informed consent prior to performance of study-specific procedures or assessments * Patients with at least one measurable disease, as defined by RECIST 1.1 * Fresh or archived tumor tissue should be provided for all subjects for biomarker analysis before or during treatment with pazopanib. * Adequate organ system function as defined as: * Subjects may not have had a transfusion within 7 days of screening assessment. * Subjects receiving anticoagulant therapy are eligible if their International Normalized Ratio (INR) is stable and within the recommended range for the desired level of anticoagulation. * Concomitant elevations in bilirubin and aspartate aminotransferase (AST) or alanine aminotransferase (ALT) above 1.0 x ULN are not permitted. Patients with Gilbert's disease and elevation of indirect bilirubin only can be considered like patients with normal bilirubin. * Compliance of the patient Exclusion Criteria: * Other malignancy. (Patients who have undergone prior radical or partial nephrectomy for RCC are allowed). Subjects who have had another malignancy and have been disease-free for five years, or subjects with a history of completely resected non-melanomatous skin carcinoma or successfully treated in situ carcinoma are eligible. * Prior systemic treatment for renal cell carcinoma. (NB: all treatments, neo-adjuvant, adjuvant or for locally advanced or metastatic RCC are not permitted.) * History or clinical evidence of central nervous system (CNS) metastases or leptomeningeal carcinomatosis, except for individuals who have previously-treated CNS metastases, are asymptomatic, and have had no requirement for steroids or anti-seizure medication for 6 months prior to first dose of study drug. Screening with CNS imaging studies (computed tomography (CT) or magnetic resonance imaging (MRI) is required only if clinically indicated or if the subject has a history of CNS metastases. * Clinically significant gastrointestinal abnormalities that may increase the risk for gastrointestinal bleeding * Clinically significant gastrointestinal abnormalities that may affect absorption of investigational product including, but not limited to: Malabsorption syndrome, major resection of the stomach or small bowel. * Presence of uncontrolled infection (\> grade 2 NCI-CTCAE Version 4.03). * Corrected QT interval (QTc) \> 480 msecs using Bazett's formula * History of any one or more of the following cardiovascular conditions within the past 6 months: * Myocardial infarction * Cardiac angioplasty or stenting * Unstable angina * Coronary artery bypass graft surgery * Symptomatic peripheral vascular disease * Class III or IV congestive heart failure, as defined by the New York Heart Association (NYHA) * Poorly controlled hypertension * History of cerebrovascular accident including transient ischemic attack (TIA), pulmonary embolism or untreated deep venous thrombosis (DVT) within the past 6 months. Note: Subjects with recent DVT who have been treated with therapeutic anti-coagulating agents for at least 6 weeks are eligible * 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 diathesis. * Known endobronchial lesions or lesions infiltrating major pulmonary vessels * Hemoptysis in excess of 2.5 ml (or one half teaspoon ) within 8 weeks prior to first dose of study drug * Any serious or unstable pre-existing medical, mental, or other condition, medical, social or mental impairment or drug abuse that could comprise or interfere with the subject's safety, provision of informed consent, or compliance to study procedures. * Unable or unwilling to discontinue use of prohibited medications for at least 14 days or five half-lives of a drug (whichever is longer) prior to the first dose of study drug and for the duration of the study. * Simultaneous participation in another clinical drug study * Known infection with Human Immunodeficiency Virus (HIV) or chronic hepatitis B or C * Pregnant or breast-feeding women. Female subjects of childbearing potential need to be negatively tested prior and as close to the start of therapy as possible, at least within 14 days. Women participating in this trial are required to use adequate contraception. Female subjects who are lactating should discontinue nursing prior to the first dose of study drug and should refrain from nursing throughout the treatment period and for 14 days following the last dose of study drug * Subjects who are unable to take oral medication * Known hypersensitive reaction to any of the components of study treatments