A Study to Evaluate Pazopanib as an Adjuvant Treatment for Localized Renal Cell Carcinoma (RCC) (PROTECT)

Inclusion Criteria:

• Signed written informed consent
• Diagnosis of RCC with clear-cell or predominant clear-cell histology

• Subjects with non-metastatic disease (M0) fulfilling any of the following combinations of pathologic staging based on American Joint Committee on Cancer (AJCC) TNM staging version 2010 and Fuhrman nuclear grading.

  • pT2, G3 or G4, N0; or,
  • pT3, G any, N0; or,
  • pT4, G any, N0; or,
  • pT any, G any, N1

• Fulfill all of the following criteria of disease-free status at baseline:

  • Had complete gross surgical resection of all RCC via radical or partial nephrectomy using either open or laparoscopic technique.
  • Baseline imaging of chest, abdomen and pelvis shows no metastasis or residual tumor lesions as confirmed centrally by an independent radiologist.
• Received no prior adjuvant or neo-adjuvant treatment for RCC
• Recovered from nephrectomy: any surgery related toxicities should be reduced to ≤ grade 1 per NCI Common Terminology Criteria for Adverse Events (CTCAE) (Version 4)
• Karnofsky performance scale (KPS) of ≥ 80
• Adequate organ system function

Exclusion Criteria:

• History of another malignancy. Exception: Subjects who have had another malignancy and have been disease-free for 5 years, or subjects with a history of completely resected non-melanomatous skin carcinoma or successfully treated in situ carcinoma are eligible

• Clinically significant gastrointestinal abnormalities that may increase the risk for gastrointestinal bleeding including, but not limited to:

  • Active peptic ulcer disease
  • Inflammatory bowel disease (e.g. ulcerative colitis, Crohn's disease), 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
• Active diarrhea of any grade

• 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
• History of human immunodeficiency virus (HIV) infection
• History of active hepatitis
• Presence of uncontrolled infection.

• History of any one or more of the following cardiovascular conditions within the past 6 months:

  • Cardiac angioplasty or stenting
  • Myocardial infarction
  • Unstable angina
  • Coronary artery bypass graft surgery
  • Symptomatic peripheral vascular disease
• History of Class III or IV congestive heart failure, as defined by the New York Heart Association Classification of Congestive Heart Failure
• History of cerebrovascular accident including transient ischemic attack (TIA), pulmonary embolism or untreated deep venous thrombosis (DVT) within the past 6 months.
• Corrected QT interval (QTc) > 480 milliseconds (msec)
• Poorly controlled hypertension, defined as systolic blood pressure (SBP) of ≥140 mmHg or diastolic blood pressure (DBP) of ≥ 90mmHg.

Note: Initiation or adjustment of antihypertensive medication(s) is permitted prior to study entry. Blood pressure (BP) must be re-assessed on two occasions that are separated by a minimum of 1 hour; on each of these occasions, the mean (of 3 readings) SBP / DBP values from each BP assessment must be <140/90 mmHg in order for a subject to be eligible for the study (see Section 7.6.2 for instruction on blood pressure measurement and obtaining mean blood pressure values).

• Evidence of active bleeding or bleeding diathesis
• Any serious and/or unstable pre-existing medical, psychiatric, or other condition that could interfere with 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 treatment and for the duration of the study.
• Concurrent therapy given to treat cancer including treatment with an investigational agent or concurrent participation in another clinical trial involving anti-cancer investigational drug.
• Administration of an investigational drug within 30 days or 5 half-lives, whichever is longer, preceding the first dose of study treatment.
• Have a known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to pazopanib or excipients that in the opinion of the investigator contraindicates their participation.
• Prior or current use of systemic anti-VEGF inhibitors, cytokines (e.g. interferon, interleukin 2).