Pazopanib Hydrochloride and Bevacizumab in Treating Patients With Previously Untreated Metastatic Kidney Cancer

Prior treatment

• Concurrent use of another anti-cancer drug including an investigational anti-cancer agent
• Major surgery within 28 days prior to treatment or major surgery planned during the next 6 months
• Subjects currently on anti-coagulation therapy are not eligible
• Unable to discontinue the use of prohibited medications
• Received an investigational agent within 30 days prior to enrollment

Other illness

• Subjects diagnosed with another cancer in the past 3 years; excluding basal cell carcinoma or squamous cell carcinoma, of skin which were completely cured by resection
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic or psychiatric illness/social situations that would limit compliance with study requirements
• History of deep vein thrombosis (DVT) or pulmonary embolism (PE) in the past 6 months
• Evidence of active bleeding or bleeding disorder
• Any condition which in the investigator's opinion deems the subject an unsuitable candidate to receive study drug

Lab values

• Prior VEGF targeted therapies for renal cell carcinoma (RCC) including adjuvant or neoadjuvant treatments; in phase 1 only, one prior therapy with high dose IL-2 or anti-programmed cell death (PD)-1 compound alone or in combination with cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) targeting drug is allowed on the trial
• History of any of the following cardio-vascular condition:
  • Myocardial infarction (MI)
  • Unstable angina
  • Coronary artery bypass grafting (CABG)-unless patient had a negative stress test within 6 months of screening
  • Coronary angioplasty or stenting
  • Symptomatic peripheral arterial disease (PAD)
  • History of symptomatic chronic congestive heart failure (CHF)
  • History of cerebrovascular accidents including transient ischemic attacks (TIA)
  • Corrected QT interval (QTc) \> 480 msec
  • Uncontrolled hypertension (systolic blood pressure \[BP\] \> 150 mm Hg or diastolic BP of \> 90 mm Hg); if the screening BP is elevated, adjustments in anti-hypertensives are permitted and a re-screening will be permitted for BP assessment with three consecutive values obtained 2 minutes apart; the 3 values have to be below 150/90 mm Hg for eligibility and can only be obtained after 2 days of the last change in anti-hypertensive medication; use of clonidine is not permissible for adjusting the BP during this period
• Subjects should not have packed red blood cells (PRBC) or platelet transfusion within 14 days of the screening

Other

• Subjects with known brain metastases should be excluded from this clinical trial
• Pregnant or nursing female subjects
• Unwilling or unable to follow protocol requirements

• Biopsy/pathology-proven clear cell renal cell carcinoma (CCRCC) with metastases
• Have an Eastern Cooperative Oncology Group (ECOG) performance status =\< 1
• Hemoglobin \>= 10 gm/dL
• Absolute neutrophil count (ANC) \>= 1.5 x 10\^9/L
• Platelets \>= 100 x 10\^9/L
• Total bilirubin =\< upper limit of normal (ULN)
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =\< ULN
• International normalization ratio (INR) and activated partial thromboplastin time (aPTT) \< 1.2 x ULN
• Serum creatinine \< 1.5 mg/dL or if serum creatinine \> 1.5 mg/dL then calculate creatinine clearance (CrCL) \> 30 mL/min
• Urine protein to creatinine ratio =\< 1 (if urine protein creatinine ratio is \> 1, then a 24-hour urine total protein must be assessed; subjects will be ineligible if the 24-hour urine protein is found to be \> 1 gm)
• Normal cardiac ejection fraction (\> 50%) by multi gated acquisition scan (MUGA) or echocardiogram
• Have measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria present
• Ability to swallow and retain oral medication
• Subjects of child-bearing potential must agree to use adequate contraceptive methods (e.g., hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately
• Subject or legal representative must understand the investigational nature of this study and sign an Independent Ethics Committee/Institutional Review Board approved written informed consent form prior to receiving any study related procedure