Inclusion Criteria:

- Histologic documentation: renal cell carcinoma with some component of clear cell
histology

- Stage: locally advanced (defined as disease not amenable to curative surgery or
radiation therapy) or metastatic renal cell carcinoma (RCC) (equivalent to stage IV
RCC, according to American Joint Committee on Cancer [AJCC] staging)

- Eligible patients must be intermediate/poor risk, per the International Metastatic
Renal Cell Carcinoma (mRCC) Database Consortium (Heng) criteria defined as one or
more of the following six factors:

- Time from diagnosis of RCC to systemic treatment < 1 year

- Hemoglobin < the lower limit of normal (LLN)

- Corrected calcium > the upper limit of normal (ULN)

- Karnofsky performance status < 80%

- Neutrophil count > ULN

- Platelet count > ULN

- No radiographic evidence of cavitating pulmonary lesion(s)

- No tumor in contact with, invading or encasing any major blood vessels; tumor
abutting the vessels is acceptable

- No evidence of tumor invading the gastrointestinal (GI) tract (esophagus, stomach,
small or large bowel, rectum or anus), or any evidence of endotracheal or
endobronchial tumor within 28 days prior to registration

- No prior systemic treatment for RCC; supportive therapies such as bisphosphonates
(zoledronic acid) or denosumab are permitted

- Patients must not have had a major surgical procedure or significant traumatic injury
within 4 weeks prior to study registration, and must have fully recovered from any
such procedure; the following are not considered to be major procedures:
thoracentesis, paracentesis, port placement, laparoscopy, thoracoscopy, bronchoscopy,
endoscopic ultrasonographic procedures, mediastinoscopy, skin biopsies, incisional
biopsies, imaging-guided biopsy for diagnostic purposes, and routine dental
procedures

- Radiation

- to the brain, thoracic cavity, abdomen, or pelvis must be completed within 90
days before registration;

- to bone must be completed within 14 days before registration; and

- to any other sites must be completed within 28 days before registration

- No chronic concomitant treatment of strong cytochrome P450, family 3, subfamily A,
polypeptide 4 (CYP3A4) inducers (e.g., dexamethasone, phenytoin, carbamazepine,
rifampin, rifabutin, rifapentin, phenobarbital, and St. John's Wort)

- Patients must have measurable disease by Response Evaluation Criteria in Solid Tumors
(RECIST) criteria; lesions that can be accurately measured in at least one dimension
(longest diameter to be recorded) as >= 2 cm with conventional techniques or as >= 1
cm with spiral computed tomography (CT) scan

- No active brain metastases; patients with treated, stable brain metastases for at
least three months are eligible as long as they meet the following criteria:

- Treated brain metastases are defined as having no ongoing requirement for
steroids and no evidence of progression or hemorrhage after treatment for at
least 3 months, as ascertained by clinical examination and brain imaging
(magnetic resonance imaging [MRI] or CT); (stable dose of anticonvulsants are
allowed); treatment for brain metastases may include whole brain radiotherapy
(WBRT), radiosurgery (RS; Gamma Knife, linear accelerator [LINAC], or
equivalent) or a combination as deemed appropriate by the treating physician;
patients with central nervous system (CNS) metastases treated by neurosurgical
resection or brain biopsy performed within 3 months prior to registration are
not eligible

- Baseline brain imaging (MRI/CT) is required

- No serious non-healing wound, ulcer, or bone fracture

- No arterial thrombotic events within 6 months prior to registration, including
transient ischemic attack (TIA), cerebrovascular accident (CVA), peripheral arterial
thrombus, unstable angina or angina requiring surgical or medical intervention in the
6 months prior to registration, or myocardial infarction (MI); patients with
clinically significant peripheral artery disease (i.e., claudication on less than one
block), significant vascular disease (i.e., aortic aneurysm, history of aortic
dissection), or any other arterial thrombotic event are ineligible

- No history of pulmonary embolism or untreated deep venous thrombosis (DVT) within 6
months prior to registration; note: patients with recent DVT who have been treated
with therapeutic anticoagulanting agents for at least 6 weeks are eligible; patients
receiving warfarin are not eligible, but could be switched to low molecular weight
heparin if acceptable to the treating physician

- No inadequately controlled hypertension (defined as a blood pressure of >= 150 mmHg
systolic and/or >= 90 mmHg diastolic), or any prior history of hypertensive crisis or
hypertensive encephalopathy

- No New York Heart Association (NYHA) class >= 2 congestive heart failure

- Ejection fraction on echocardiogram (Echo) or multi gated acquisition scan (MUGA) >
50%

- No corrected QT interval calculated by the Fridericia formula (QTcF) > 500 ms within
28 days before randomization; note: if initial QTcF is found to be > 500 ms, two
additional electrocardiograms (EKGs) separated by at least 3 minutes should be
performed; if the average of these three consecutive results for QTcF is =< 500 ms,
the subject meets eligibility in this regard

- No evidence of active bleeding or bleeding diathesis, or hemoptysis within 6 weeks
prior to registration

- No history of abdominal fistula, gastrointestinal perforation or intra-abdominal
abscess within 6 months prior to registration

- No active peptic ulcer disease, within 28 days before registration

- No inflammatory bowel disease (including ulcerative colitis and Crohn's disease),
diverticulitis, cholecystitis, symptomatic cholangitis or appendicitis within 28 days
before registration

- No malabsorption syndrome within 28 days before registration

- No untreated hypothyroidism; patients with hypothyroidism on therapy are required to
have thyroid stimulating hormone (TSH) within normal limits

- No radiologic or clinical evidence of pancreatitis

- Patients who are pregnant or nursing are not eligible; women of child bearing
potential must have a negative serum or urine pregnancy test within 16 days prior to
registration; women of child-bearing potential include:

- Any female who has experienced menarche and who has not undergone surgical
sterilization (hysterectomy, bilateral tubal ligation or bilateral oophorectomy)
or is not postmenopausal (defined as amenorrhea >= 12 consecutive months)

- Women on hormone replacement therapy (HRT) with documented serum follicle
stimulating hormone (FSH) level > 35m IU/mL

- Women who are using oral, implanted or injectable contraceptive hormones or
mechanical products such as an intrauterine device or barrier methods
(diaphragm, condoms, spermicides) to prevent pregnancy or practicing abstinence
or where partner is sterile (e.g., vasectomy)

- Performance status: Eastern Cooperative Oncology Group (ECOG) 0-2 or Karnofsky score
>= 60%

- Absolute neutrophil count (ANC) >= 1,500/uL

- Platelet count >= 100,000/uL

- Hemoglobin >= 9 g/dL; patients may not have had a transfusion within 7 days prior to
screening assessment

- Total bilirubin =< 1.5 x upper limits of normal

- Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 2.5 x ULN

- Serum creatinine =< 1.5 x ULN, OR calculated creatinine clearance >= 30 mL/minute
(modified Cockroft and Gault formula)

- Urine protein to creatinine (UPC) ratio < 1.0; if UPC >= 1, then a 24-hour urine
protein must be assessed; eligible patients must have a 24-hour urine protein value <
1 g

- Total serum calcium < 12 mg/dL

- International normalized ratio (INR) =< 1.2 x ULN; subjects receiving anticoagulant
therapy are eligible if their INR is stable and within the recommended range for the
desired level of anticoagulation

- TSH within normal limits (WNL); supplementation is acceptable to achieve a TSH WNL