A Phase I/ II Trial of Pazopanib Alternating With Bevacizumab in Treatment-Naive Metastatic Clear Cell Renal Cell Carcinoma Patients

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 ([NR) 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

- 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)

- 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