| Exclusion Criteria: | 1) Primary tumor in situ: Subjects must have their primary tumor resected to be eligible for this study
2) Known history of central nervous system metastases. An MRI or CT scan of the brain or head will be performed within 28 days of randomization.
3) History of arterial or venous thrombosis within 6 months prior to randomization
4) History of bleeding diathesis or clinically significant bleeding within 14 days of randomization
5) Previous treatment (excluding surgery and palliative radiotherapy) for advanced or metastatic renal cell carcinoma
6) Focal radiation therapy for palliation of pain from bony metastases within 14 days of randomization.
7) Subjects who received radiation therapy must have recovered from all radiation induced toxicities prior to randomization
8) Currently or previously treated with sorafenib or other small molecule inhibitors of VEGF including, but not limited to AMG 706 (motesanib), SU11248 (sunitinib), PTK787 (vatalinib), AZD 2171, AEE-788. Currently or previously treated with bevacizumab
9) Currently or previously treated with AMG 386, or other molecules that inhibit the angiopoietins or Tie2 receptor including but not limited to, AZD-5180, XL-820, CEP 11981/SSR-106462, BSF-466,895, CGI-1842, LOC-590, XL-184, or CP- 8681596
10) Concomitant or use within 30 days prior to randomization of any strong inducer of CYP3A4 including, but not limited to, rifampin, St. John's wort, phenytoin, carbamazepine, phenobarbital and dexamethasone
11) Known ongoing pancreatits
12) Myocardial infarction, cerebrovascular accident, transient ischemic attack, percutaneous transluminal coronary angioplasty/stent, congestive heart failure, grade 2 or greater peripheral vascular disease, arrhythmias not controlled by outpatient medication, or unstable angina within 1 year prior to randomization
13) Major surgery within 30 days before randomization or still recovering from prior surgery
14) History of allergic reactions to bacterially produced proteins
15) Pregnant (i.e., positive beta-human chorionic gonadotropin test) or is breast feeding
16) Exclude subjects with a history of prior malignancy, except: a.) Malignancy treated with curative intent and with no known active disease present for = 3 years before enrollment and felt to be at low risk for recurrence by treating physician; b.) Adequately treated non-melanomatous skin cancer or lentigo maligna without evidence of disease; c.) Adequately treated cervical carcinoma in situ without evidence of disease; d.) Prostatic intraepithelial neoplasia without evidence of prostate cancer
17) Minor surgical procedures, placement of access device, or fine needle aspiration within 7 days of first dose.
18) Uncontrolled hypertension as defined as diastolic > 90 mmHg OR systolic >140 mmHg. Anti-hypertensive medications are permitted.
19) Known active or ongoing infection within 14 days before randomization
20) Subject known to have tested positive for HIV
21) Subject known to have chronic hepatitis
22) Any condition which in the investigator's opinion makes the subject unsuitable for study participation
23) History of pulmonary hemorrhage or gross hemoptysis (1/2 teaspoon or more of bright red blood) within 6 months before randomization
24) Concurrent or prior (within 1 week before randomization) anticoagulation therapy, excluding aspirin and anti-platelet agents. The concurrent use of low molecular weight heparin or low dose warfarin (ie, </= 1 mg daily) for prophylaxis against thrombosis is acceptable while on study.
25) Other investigational procedures are excluded.
26) Subject not consenting to the use of highly effective contraceptive, e.g. double barrier method (i.e. condom plus diaphragm) precautions during the course of the study and for 6 months after administration of the last study medication
27) Subject currently is enrolled in or has not yet completed at least 30 days since ending other investigational device or drug study(s), or subject is receiving other investigational agent(s)
28) Subject has known sensitivity to any of the products to be administered during dosing
29) Subject has previously been randomized onto this study
30) Subject will not be available for follow-up assessment
31) Subject has any kind of disorder that compromises the ability of the subject to give written informed consent and/or to comply with study procedures
32) Subject has any kind of disorder that compromises the ability of the subject to give written informed consent and/or to comply with study procedures |