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

Inclusion Criteria:

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

Exclusion Criteria:

Subjects with known brain metastases should be excluded from this clinical trial
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
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
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
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 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
History of deep vein thrombosis (DVT) or pulmonary embolism (PE) in the past 6 months
Subjects should not have packed red blood cells (PRBC) or platelet transfusion within 14 days of the screening
Evidence of active bleeding or bleeding disorder
Subjects currently on anti-coagulation therapy are not eligible
Unable to discontinue the use of prohibited medications
Pregnant or nursing female subjects
Unwilling or unable to follow protocol requirements
Any condition which in the investigator's opinion deems the subject an unsuitable candidate to receive study drug
Received an investigational agent within 30 days prior to enrollment