A Randomized, Double-blind, Placebo-controlled Phase III Study to Evaluate the Efficacy and Safety of Pazopanib as Adjuvant Therapy for Subjects With Localized or Locally Advanced RCC Following Nephrectomy
- 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
- 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
- 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
- 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
- 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
- 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,