| Exclusion Criteria: | 1) Subject has received anti-cancer therapy within 21 days or 5 half lives, whichever is shorter, prior to study drug administration. Anti-cancer therapies include but are not limited to: investigational agents, immunotherapy, radiation therapy, traditional Chinese medicine/herbal remedies, hormonal, "targeted" agents (i.e., erlotinib, imatinib) or biologic therapy.
2) Subject has received cytotoxic chemotherapy (i.e., alkalating agents, microtubule inhibitors, antimetabolites) within 21 days prior to study drug administration. In addition, subject has not recovered to less than or equal to Grade 1 clinically significant adverse effects/toxicities of previous therapy.
3) Subject has had major surgery within 21 days prior to study drug administration.
4) Subject has untreated brain or meningeal metastases. CT scans are not required to rule out brain or meningeal metastases unless there is a clinical suspicion of central nervous system disease. Subjects with treated brain metastases that are radiographically or clinically stable for at least 4 weeks after therapy and have no evidence of cavitation or hemorrhage in the brain lesion are eligible providing that they are asymptomatic and do not require corticosteroids (must have discontinued steroids at least 1 week prior to registration).
5) Subject has received a tyrosine kinase inhibitor (TKI) other than sunitinib or sorafenib. Prior use of Avastin is allowed.
6) The subject has proteinuria CTC grade > 1 as measured by a UPC ratio of > 1 and 24 hour urine collection during baseline assessment (if the UPC ratio is > 1, a 24-hour urine collection should be performed).
7) The subject is receiving therapeutic anticoagulation therapy. Low dose anti-coagulation (eg, low dose Coumadin) for catheter prophylaxis only will be permitted. No low molecular weight (LMW) heparin is allowed.
8) The subject has a history of/or currently exhibits clinically significant cancer related events of bleeding (eg, hematuria, hemoptysis). The subject has a recent history of (within 4 weeks of Study Day 1) or currently exhibits other clinically significant signs of bleeding.
9) The subject currently exhibits symptomatic or persistent, uncontrolled hypertension defined as diastolic blood pressure (BP) > 90 mmHg; or systolic blood pressure (BP) > 140 mmHg. Subjects may be re-screened if BP is shown to be controlled with or without intervention.
10) The subject has a history of myocardial infarction within 6 months of Study Day 1.
11) The subject has a documented left ventricular (LV) Ejection Fraction < 50%.
12) The subject has known autoimmune disease with renal involvement (eg, Lupus).
13) Female subjects who are pregnant or breast feeding.
14) Subject is receiving anti-retroviral therapy for HIV.
15) Subject has a clinically significant uncontrolled condition(s) including but not limited to: a) active uncontrolled infection, b) Class III or IV heart failure as defined by the New York Heart Association functional classification system, c) unstable angina pectoris or cardiac arrhythmia,d) history of adrenal insufficiency, e) psychiatric illness/social situation that would limit compliance with study requirements, f) Active, ulcerative colitis, Crohn's disease, Celiac disease or any other conditions that interfere with absorption;
16) (#13 cont'd) g) Subject has a medical condition, which in the opinion of the study investigator places them at an unacceptably high risk for toxicities. |