A Study to Evaluate Pazopanib as an Adjuvant Treatment for Localized Renal Cell Carcinoma (RCC)
Condition: Renal Cell Carcinoma (RCC); Cancer
MeSH terms: Carcinoma; Carcinoma, Renal Cell
Intervention: pazopanib; placebo; pazopanib; placebo
Intervention description: Pazopanib monohydrochloride salt was supplied as aqueous, film-coated tablets containing 200 mg of the free base. The 200 mg tablets were oval-shaped and white in color.; Placebo matching pazopanib was supplied as aqueous, film-coated tablets containing 200 mg of the free base. The 200 mg tablets were oval-shaped and white in color.; Pazopanib 600 mg daily initial dose for 8-12 weeks, dose can be escalated to 800 mg daily based on safety evaluation.; placebo matching pazopanib daily initial dose for 8-12 weeks, dose can be escalated to 800 mg daily based on safety evaluation.
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 1538.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: anti-angiogenic agent; renal cell carcinoma; pazopanib; adjuvant therapy; VEGFR inhibitor; localized or locally; advanced renal cell carcinoma (RCC) following nephrectomy; advanced RCC; Cancer

Summary:

      This randomized Phase III study is to evaluate whether pazopanib compared with placebo can
      prevent or delay recurrence of kidney cancer in patients with moderately high or high risk of
      developing recurrence after undergoing kidney cancer surgery.
    

Eligibility criteria:

        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).