| Exclusion Criteria: | 1) Untreated or symptomatic brain metastases.
2) Prior malignancy (other than thyroid cancer, in situ cervical cancer, or basal cell cancer of the skin), unless treated with curative intent and without evidence of disease for >/ = 3 years before study day 1.
3) Myocardial infarction, or unstable or uncontrolled disease or condition related to or impacting cardiac function (eg, unstable angina, congestive heart failure [New York Heart Association > Class II]) within 1 year before study day 1.
4) Arterial thrombosis, deep vein thrombosis or Pulmonary Embolus within 1 year before study day 1.
5) History of hemoptysis within 6 months before study day 1. Evidence of transmural invasion into the trachea or esophagus, or circumferential involvement of carotid or jugular vessels at the time of screening before study day 1. (ie, at least 1/2 teaspoon of bright red expectorated blood suspected to be from tumoral bleeding in subjects with known pulmonary metastases)
6) Major surgical procedure within 30 days before study day 1.
7) Known positive test for human immunodeficiency virus (HIV).
8) Absolute neutrophil count (ANC) < 1,500/uL • platelet count < 100,000/uL • hemoglobin < 9 g/dL • serum creatinine > 2.0 mg/dL (> 177 µmol/L) or calculated clearance < 40 mL/min • urine protein quantitative value of 30 mg/dL in urinalysis, unless a 24-hour urine protein is < 500 mg/day • aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 2.5 x upper limits of normal (ULN), or AST or ALT > 5.0 x ULN if secondary to documented liver metastasis • total bilirubin > 2 x ULN.
9) Prothrombin time international normalized ratio >/ = 2.0 or partial thromboplastin time > 1.5 X ULN
10) Previous exposure to AMG 706, other tyrosine kinase inhibitors of RET or VEGF receptor.
11) Treatment with coumarin anticoagulants, including warfarin (ie, > 2 mg/day) within 7 days before study day 1.
12) St John's Wort or any herbal therapy containing St John's Wort within 7 days before study day 1.
13) Treatment with rifampin or phenobarbital within 14 days before study day 1.
14) Treatment with or consumption of strong CYP3A4 inhibitors or inducers such as ketoconazole, itraconazole, erythromycin, clarithromycin, nefazodone, cyclosporine, grapefruit (ie, whole fruit or fruit juice), and any HIV protease inhibitors within 7 days before study day 1.
15) Treatment with anticancer therapy within 30 days before study day 1 [including chemotherapy, retinoid therapy (eg, all-trans retinoic acid, isotretinion), radiation therapy, hormonal therapy for thyroid cancer other than chronic thyroid stimulating hormone suppression (eg, thyroxine), or tumor-directed antibody therapy].
16) Any condition which in the investigator's opinion makes the subject unsuitable for study participation.
17) Not yet completed at least 30 days since ending other investigational device/drug trial(s), or subject is receiving other investigational treatments.
18) Pregnancy (ie, positive beta human chorionic gonadotropin test) or breast feeding.
19) Not using adequate contraceptive precautions during the treatment period.
20) Unable to swallow oral medications.
21) Previously enrolled into this study.
22) Any disorder that compromises the ability of the subject to give written informed consent and/or to comply with study procedures.
23) treatment with immune modulators such as tacrolimus and cyclosporine within 7 days before study day 1 |