Alternative Schedule Sunitinib Malate in Treating Patients with Advanced or Metastatic Kidney Cancer or That Cannot Be Removed by Surgery

Inclusion Criteria

• Histologically confirmed renal cell carcinoma (RCC)
• One of the two following populations: * High risk for recurrence of RCC after nephrectomy, in the opinion of the investigator, OR * Locally advanced, unresectable or metastatic disease, in the opinion of the investigator, and good or intermediate risk by Clinical Trial Independent Data Monitoring Committee (IDMC) Heng Criteria
• Karnofsky performance status (KPS) >= 80
• Appropriate for treatment with sunitinib in the opinion of the treating physician
• Able to swallow sunitinib and comply with study requirements
• Able to walk and jog on a treadmill, in the opinion of the treating physician
• Must be able to complete an acceptable cardiopulmonary exercise test (CPET) at baseline defined as at least one of the following: * Achieving a plateau in oxygen consumption concurrent with an increase in power output; * Respiratory exchange ratio >= 1.1 (RER); * Volitional exhaustion with a rating of perceived exertion >= 17 (RPE)
• Absolute neutrophil count >= 1,200/uL
• Hemoglobin >= 9 g/dL
• Platelets >= 75,000/uL
• Total bilirubin =< 1.5 x institutional upper limit of normal
• Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransaminase (ALT) (serum glutamate pyruvate transaminase [SGPT]) < 2.5 x institutional upper limit of normal
• Urine protein creatinine (UPC) ratio of < 1
• Creatinine =< 2.0 OR creatinine clearance > 30 mL/min/1.73 m^2 for subjects with creatinine levels above institutional normal
• Left ventricular ejection fraction (LVEF) >= lower limit of institutional normal as assessed by echocardiography
• For the sixteen patients who elect to participate in the optional technology portion involving electronic step counts and blood pressure monitoring, the patient must have a Bluetooth-enabled smart phone, which is compatible with the wireless health monitors
• For women of childbearing potential (WOCBP) must have a negative serum pregnancy test prior to the start of the study; women of childbearing potential (WOCBP) must agree to follow instructions for method(s) of contraception for the duration of the study; medically acceptable contraceptives include: (1) surgical sterilization (such as a tubal ligation or hysterectomy), (2) approved hormonal contraceptives (such as birth control pills, patches, implants or injections), (3) barrier methods (such as a condom or diaphragm) used with a spermicide, or (4) an intrauterine device (IUD); contraceptive measures such as Plan B (TM), sold for emergency use after unprotected sex, are not acceptable methods for routine use; if you do become pregnant during this study or if you have unprotected sex, you must inform your study physician immediately
• For men who are sexually active, must agree to use a two medically acceptable forms of birth control (one of which must include a condom as a barrier method of contraception) in order to be in this study; medically acceptable contraceptives include: (1) surgical sterilization (such as a vasectomy), or (2) a condom used with a spermicide; contraceptive measures such as Plan B (TM), sold for emergency use after unprotected sex, are not acceptable methods for routine use; men must also agree to inform their partner of the potential for harm to an unborn child; she should know that if pregnancy occurs, the subject will need to report it to the study doctor, and she should promptly notify her doctor; the study doctor will ask if the subject’s partner is willing to provide updates on the progress of the pregnancy and its outcome; if the subject’s partner agrees, this information will be provided to Pfizer, Inc. for safety monitoring follow-up

Exclusion Criteria

• Any prior anti-vascular endothelial growth factor (VEGF) therapies (i.e., sunitinib, sorafenib, pazopanib, axitinib, cabozantinib, bevacizumab, etc.), including in the adjuvant or neoadjuvant setting
• Prior systemic therapy for advanced RCC; however, treatment with immunotherapy (i.e., high-dose bolus IL-2, ipilimumab + nivolumab, etc.) is allowed
• Subjects who are receiving any other investigational agents
• Subjects who are receiving strong CYP3A4 inhibitors or CYP3A4 inducers
• Radiotherapy within 2 weeks prior to taking the first dose of study drug, or those who have not recovered from adverse events due to agents administered more than 2 weeks earlier
• Central nervous system (CNS) metastases at baseline, with the exception of those subjects who have previously treated CNS metastases (surgery +/- radiotherapy, radiosurgery, or gamma knife) and who meet both of the following criteria: * Are asymptomatic, and * Have no requirement for steroids or enzyme-inducing anti-convulsants in the prior 28 days
• Clinically significant gastrointestinal abnormalities that may increase the risk for gastrointestinal bleeding including, but not limited to: * Active peptic ulcer disease * Known intraluminal metastatic lesion(s) with risk of bleeding * 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
• 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 * Class III or IV congestive heart failure, as defined by the New York Heart Association (NYHA)
• Absolute contraindications to cardiopulmonary exercise testing and/or aerobic training, as determined by the attending oncologist: * Absolute contraindications ** Uncontrolled arrhythmia causing symptoms or hemodynamic compromise ** Recurrent syncope ** Active endocarditis ** Acute myocarditis or pericarditis ** Symptomatic severe aortic stenosis ** Uncontrolled heart failure ** Suspected dissecting aneurysm ** Uncontrolled asthma ** Pulmonary edema ** Room air desaturation at rest =< 85% ** Respiratory failure ** Acute non-cardiopulmonary disorders that may affect exercise performance or be aggravated by exercise (i.e., infection, renal failure, thyrotoxicosis) ** Mental impairment leading to inability to cooperate
• Poorly controlled hypertension (defined as systolic blood pressure [SBP] of > 150 mmHg or diastolic blood pressure [DBP] of > 90 mmHg)
• History of cerebrovascular accident including transient ischemic attack (TIA), pulmonary embolism, or untreated deep venous thrombosis (DVT) within the past 6 months
• Major surgery or trauma within 28 days prior to first dose of investigational product and/or presence of any non-healing wound, fracture, or ulcer (procedures such as catheter placement are not considered to be major surgery)
• Osseous metastatic disease with unacceptable risk of impending fracture due to study assessments, in the opinion of the investigator
• Evidence of active bleeding or bleeding diathesis
• Known endobronchial lesions and/or lesions infiltrating major pulmonary vessels that increase the risk of pulmonary hemorrhage