Pazopanib Hydrochloride in Treating Patients With Metastatic Kidney Cancer Who Have No Evidence of Disease After Surgery
Condition: Clear Cell Renal Cell Carcinoma; Stage IV Renal Cell Cancer AJCC v7
MeSH terms: Carcinoma; Carcinoma, Renal Cell
Intervention: Pazopanib; Placebo Administration
Intervention description: Given PO; Given PO
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 129.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: pazopanib; metastatic renal cell carcinoma; double-blind placebo control

Summary:

      This randomized phase III trial studies how well pazopanib hydrochloride works compared to
      placebo in treating patients with kidney cancer that has spread to other parts of the body
      and have no evidence of disease after surgery. Pazopanib hydrochloride may stop the growth of
      tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow
      to the tumor.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patient must have pathologically confirmed renal cell carcinoma with a clear cell
             component; pure papillary and chromophobe histologies are excluded; there must be
             pathologic confirmation of metastatic disease in the resected metastasectomy specimen

          -  Patient must have undergone nephrectomy or partial nephrectomy to remove primary renal
             cell carcinoma (at any time in the past)

          -  Patient must have undergone surgical resection to remove one or more sites of
             metastatic disease, with successful removal of all known sites 2-12 weeks prior to
             randomization; any number of prior metastasectomies may have been performed in the
             past, so long as the most recent procedure was within the 12 weeks of registration;
             the most recent procedure may be nephrectomy for a renal primary tumor

          -  Patients with synchronous disease at initial diagnosis must have metastatic (M1)
             disease (American Joint Committee on Cancer [AJCC] 7th edition T1-4N0-1M1)

          -  Positive surgical margins are permitted if the surgeon confirms complete resection of
             gross metastatic disease, and post-operative scans are negative

          -  Patients presenting with metachronous disease may have distant metastases, regional
             lymph node or renal bed recurrence; recurrences at a partial nephrectomy resection
             site are not eligible if it is the only site of disease

          -  Patient must have no evidence of disease on post-operative imaging:

               -  A computed tomography (CT) of the chest must be obtained within 4 weeks prior to
                  randomization with or without contrast

               -  A CT of the abdomen/pelvis must be obtained within 4 weeks prior to randomization
                  with intravenous (IV) contrast (oral contrast may be added at the radiologist's
                  discretion); an magnetic resonance imaging (MRI) of the abdomen/pelvis with
                  gadolinium may be substituted for the CT if the CT with IV contrast is
                  contra-indicated

               -  An MRI of the brain with and without gadolinium must be done within 8 weeks prior
                  to randomization; a CT of the brain with and without IV contrast is permitted if
                  MRI is contra-indicated (i.e., pacemaker)

          -  Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0
             or 1 at the time of randomization

          -  Absolute granulocyte count > 1,500/mcL

          -  Platelets > 100,000/mcL

          -  Total bilirubin < 1.5 x institutional upper limit of normal (ULN)

          -  Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase
             [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT])
             < 2.5 x upper limit of normal (ULN)

          -  Calculated creatinine clearance (CrCl) > 30 mL/min

          -  Subjects must have a urine protein/creatinine (UPC) ratio < 1; if UPC >= 1, then a
             24-hour urine total protein must be obtained; subjects must have a 24-hour urine
             protein value < 1 g to be eligible; use of urine dipstick for renal function
             assessment is not acceptable

          -  All females of childbearing potential must have a blood test or urine study within 2
             weeks prior to randomization to rule out pregnancy; a female of childbearing potential
             is any woman, regardless of sexual orientation or whether they have undergone tubal
             ligation, who meets the following criteria: 1) has not undergone a hysterectomy or
             bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24
             consecutive months (i.e., has had menses at any time in the preceding 24 consecutive
             months)

          -  Women of childbearing potential and sexually active males must be strongly advised to
             use an accepted and effective method of contraception or to abstain from sexual
             intercourse for the duration of their participation in the study; should a woman
             become pregnant while participating in this study, she should inform her treating
             physician immediately; if a man impregnates a woman while participating in this study,
             he should inform his treating physician immediately

          -  Patient must be able to swallow pills and have no significant impairment in
             gastrointestinal absorption including history of gastric bypass surgery

          -  Patient must have a corrected QT (QTc) interval on electrocardiogram (ECG) =< 0.48
             seconds by Bazett's calculation (=< Common Terminology Criteria for Adverse Events
             [CTCAE] version [v.]4 grade 2) prior to randomization

          -  Patient must have a systolic blood pressure =< 140 mmHg and diastolic blood pressure
             must be =< 90 mmHg, measured within 4 weeks prior to randomization; initiation or
             adjustment of anti-hypertensives prior to starting study treatment is allowed

        Exclusion Criteria:

          -  Patients presenting with tumors within the kidneys (multiple synchronous or
             single/multiple metachronous) if there are no extrarenal sites of disease (i.e.
             potential multifocal primary disease)

          -  Prior or concurrent systemic therapy for RCC; adjuvant placebo administration is
             permitted

          -  Active peptic ulcer disease

          -  Active inflammatory bowel disease

          -  New York Heart Association (NYHA) class II or greater congestive heart failure

          -  History or current clinically apparent central nervous system metastases

          -  Pregnant or breast-feeding

          -  History of allergic reactions attributed to compounds of similar chemical or biologic
             composition to pazopanib

          -  Uncontrolled intercurrent illness including, but not limited to, ongoing or active
             infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
             arrhythmia, or psychiatric illness/social situations that would limit compliance with
             study requirements

          -  Serious or non-healing wound, ulcer, or bone fracture at the time of randomization

          -  History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess
             within 4 weeks prior to randomization

          -  History of cerebrovascular accident (CVA) within 6 months of randomization

          -  History of myocardial infarction, hospital admission for unstable angina, cardiac
             angioplasty or stenting within 6 months of randomization

          -  History of venous thrombosis within 12 weeks of randomization

          -  Taking strong cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4)
             inhibitors such as:

               -  Antibiotics: clarithromycin, telithromycin, troleandomycin

               -  Human immunodeficiency virus (HIV) antiviral protease inhibitors: ritonavir,
                  indinavir, saquinavir, nelfinavir, amprenavir, lopinavir

               -  Antifungals: itraconazole, ketoconazole, voriconazole, fluconazole

               -  Antidepressants: nefazodone

          -  History of hemoptysis in excess of 2.5 mL (1/2 teaspoon) within 8 weeks prior to
             randomization

          -  Taking drugs known to prolong the QTc interval; such drugs should be discontinued at
             least 5 half-lives prior to randomization

          -  History of other cancer within 3 years from time of randomization with the exception
             of basal cell skin cancer, squamous cell skin cancer, in situ cervical cancer, ductal
             or lobular carcinoma in situ of the breast, or resected non-invasive (Ta) urothelial
             carcinoma