| Exclusion Criteria: | 1) Concurrent therapy with any other investigational agent.
2) Known uncontrolled CNS metastases.
3) Impaired cardiac function or clinically significant cardiac disease, including any one of the following: • LVEF < 45% as determined by MUGA scan or echocardiogram • Complete left bundle branch block • Obligate use of a cardiac pacemaker • Congenital long QT syndrome • History or presence of ventricular tachyarrhythmia • Presence of unstable atrial fibrillation (ventricular response > 100 bpm). Patients with stable atrial fibrillation are eligible, provided they do not meet any of the other cardiac exclusion criteria.
4) Cont. # 3: . Clinically significant resting bradycardia (less than 50 bpm), QTc > 480 msec on screening ECG • Right bundle branch block + left anterior hemiblock (bifasicular block) • Angina pectoris less than or equal to 3 months prior to starting study drug • Acute MI less than or equal to 3 months prior to starting study drug, Other clinically significant heart disease (e.g., CHF, uncontrolled hypertension, history of labile hypertension, or history of poor compliance with an antihypertensive regimen)
5) Currently receiving treatment with any of the medications that have a relative risk of prolonging the QT interval or inducing Torsades de Points (Table 9-4) and the treatment cannot be discontinued or switched to a different medication prior to starting study drug.
6) Received chemotherapy, targeted therapy or monoclonal antibody therapy less than or equal to 4 weeks prior to starting study drug (6 weeks in the case of nitrosoureas and Mitomycin C) or has not recovered from the side effects of such therapy.
7) Received biological therapy or immunotherapy (therapeutic or diagnostic) less than or equal to 2 weeks prior to starting study drug or has not recovered from the side effects of such therapy [see 5 for monoclonal antibody therapy].
8) Received an investigational agent (therapeutic or diagnostic) less than or equal to 4 weeks prior to starting study drug or has not recovered from the side effects of such therapy [see 5 for monoclonal antibody therapy].
9) Received wide-field radiotherapy less than or equal to 4 weeks or limited-field radiation for palliation less than or equal to 2 weeks prior to starting study drug or has not recovered from side effects of such therapy. The site of radiotherapy should not be the only site of measurable disease unless there is evidence of disease progression at this site prior to entry into this study.
10) Received any hematopoietic colony-stimulating factor (e.g., G-CSF, GM-CSF) less than or equal to 2 weeks prior to starting study drug. Erythropoietin is allowed.
11) Has undergone major surgery ≤ 2 weeks prior to starting study drug or has not recovered from side effects of such surgery.
12) Malabsorption syndrome or uncontrolled gastrointestinal toxicities (nausea, diarrhea, vomiting) with toxicity greater than NCI CTCAE grade 2.
13) Pregnant or breastfeeding women.
14) History of another primary malignancy that is currently clinically significant or currently requires active intervention.
15) Chronic anticoagulation therapy with full strength ASA, Coumadin, or Heparin (low dose ASA less than or equal to 81mg, or low dose coumadin less than or equal to 1mg to maintain indwelling venous access device patency is allowed).
16) History of thromboembolic or cerebrovascular events within the last 12 months, including: TIA, CVA, DVT, PE.
17) History of melena, hematemesis, or hemoptysis within the last 3 months.
18) Known diagnosis of HIV infection (HIV testing is not mandatory)
19) Other severe, acute, or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or study-drug administration or may interfere with the interpretation of study results and, in the judgment of the investigator, make the patient inappropriate for this study.
20) The use of ketoconazole, erythromycin, carbamazapine, phenobarbital, phenytoin, rifampin, St. John's wort and quinidine is prohibited.
21) Patients with any of the following contraindications are excluded from MRI:Cardiac pacemaker • Ferromagnetic metal implants other than those approved as safe for use in the MRI scanner, ie., some types of aneurysm clips, shrapnel) • Claustrophobia• Obesity (exceeding the equipment limits) |