| Exclusion Criteria: | 1) Any disorder that compromises the ability of the subject to give written informed consent and/or to comply with the study procedures
2) Primary central nervous system (CNS) tumors or metastases
3) History or current diagnosis of a second neoplasm, except for those curatively treated with no evidence of disease for at least 1 year after the last treatment
4) History of bleeding diathesis
5) Myocardial infarction within 6 months of study day 1, symptomatic congestive heart failure (New York Heart Association > class II), unstable angina, or unstable cardiac arrhythmia requiring medication, or uncontrolled hypertension (systolic > 140 mmHg or diastolic > 90 mmHg);or left ventricular ejection fraction < 50%.
6) A baseline ECG QTcF > 480 ms
7) Active infection within 2 weeks of study enrollment (day 1)
8) Significant gastrointestinal disorder(s), in the opinion of the investigator, (e.g. Crohn's disease, ulcerative colitis, extensive gastrointestinal resection) that may influence drug absorption
9) Known positive test for HIV
10) Known acute or chronic hepatitis B or hepatitis C infection, determined by serologic tests except if a primary liver tumor is present. Subjects with a primary liver tumor may not be excluded provided there is no evidence of acute infection and hepatic function criteria are met. Exceptions to these criteria should be discussed with the sponsor prior to enrollment.
11) Unresolved toxicities from prior anti-tumor therapy, defined as not having resolved to Common Terminology Criteria for Adverse Events (CTCAE) grade 0 or 1, or to levels dictated in the eligibility criteria with the exception of alopecia
12) Anti-tumor therapy (chemotherapy, antibody therapy, molecular targeted therapy, retinoid therapy, hormonal therapy, or investigational agent) within 28 days of study day 1 (six weeks for nitrosureas, mitomycin C, or antibody or molecular targeted agents with t1/2 > 10 days); concurrent use of hormone deprivation therapy including but not limited to leuprolide acetate, anastrozole, letrozole, tamoxifen citrate for hormone-refractory prostate cancer or breast cancer is permitted.(cont. in # 13)
13) (cont. from # 12) Enrollment of subjects that have received molecularly targeted agents less than 28 days prior to study day 1 will be permitted if more than 14 days and at least 5 drug half-lives have passed prior to receiving the first dose of AMG 208.
14) Treatment with immune modulators including, but not limited to, systemic corticosteroids, cyclosporine and tacrolimus within two weeks prior to enrollment
15) Therapeutic or palliative radiation therapy within 2 weeks of study day 1
16) Concurrent or prior (within 7 days of study day 1) anticoagulation therapy (low-dose warfarin < 2 mg/day] or low molecular weight heparins for prophylaxis against central venous catheter thrombosis or aspirin [81 mg/day] is allowed)
17) Prior participation in an investigational study and/or procedure within 28 days of study day 1
18) Major surgery within 30 days of study day 1
19) Any co-morbid medical disorder that may increase the risk of toxicity, in the opinion of the investigator or sponsor
20) Concurrent or prior (within 14 days of study day 1) use of strong CYP3A4 inhibitors (including, but not limited to, ketoconazole, itraconazole, clarithromycin, indinavir, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, voriconazole)
21) Concurrent or prior (within 7 days of study day 1) Grapefruit products and other foods that are known to inhibit CYP3A4
22) Concurrent or prior (within 28 days of study day 1) use of strong CYP3A4 inducers (including, but not limited to, dexamethasone, phenytoin, carbamazepine, rifampin, rifabutin, rifapentin, phenobarbital). Subjects should also refrain from taking St John's Wort
23) Concurrent or prior (within 28 days of study day 1) use of strong P-glycoprotein and Breast Cancer Receptor Protein inhibitors (including, but not limited to elacridar and valspodar).
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