| Exclusion Criteria: | 1) Prior treatment with nilotinib or any other tyrosine kinase inhibitors or targeted agents with exception of imatinib and sunitinib (targeted agents would include the drug perifosine)
2) Treatment with any cytotoxic and/or investigational cytotoxic drug less than or equal to 4 weeks (6 weeks for nitrosurea or mitomycin C) prior to Visit 1 with the exception of imatinib and sunitinib targeted therapy
3) Prior or concomitant malignancies (primary tumor or a relapse diagnosed and treated in the last 5 years) other than GIST with the exception of previous or concomitant basal cell skin cancer or previous cervical carcinoma in situ
4) Impaired cardiac function at Visit 1 or 2, including any one of the following:LVEF < 45% or below the institutional LLN range (whichever is higher) as determined by echocardiogram at Visit 1; Complete left bundle branch block; Use of a ventricular paced cardiac pacemaker ; Congenital long QT syndrome or family history of long QT syndrome; History of or presence of significant ventricular or atrial tachyarrhythmias; Clinically significant resting bradycardia (< 50 beats per minute)
5) Continued from #6 - Impaired cardiac function at Visit 1 or 2, including any one of the following:QTc > 450 msec on screening ECG (using the QTcF formula);If QTc > 450 msec and electrolytes are not within normal ranges (electrolytes should be corrected and then the patient rescreened for QTc; Right bundle branch block plus left anterior hemiblock, bifascicular block; Myocardial infarction within 12 months prior to Visit 1; Other clinically significant heart disease (e.g., unstable angina, congestive heart failure, or uncontrolled hypertension)
6) Patients with severe and/or uncontrolled concurrent medical disease that in the opinion of the investigator could cause unacceptable safety risks or compromise compliance with the protocol e.g. impairment of gastrointestinal (GI) function, or GI disease that may significantly alter the absorption of the study drugs, uncontrolled diabetes
7) For patients who undergo PET a. Inability to remain laying down in PET scanner for up to one hour, b. Absence of at least one metastatic lesion greater than or equal to 2 cm on pre-dose CT scan or other radiographic imaging as defined by RECIST criteria
8) Absence of at least one metastatic lesion greater than or equal to 2 cm on pre-dose CT scan or other radiographic imaging as defined by RECIST criteria
9) Use of therapeutic coumarin derivatives (i.e. warfarin, acenoucumarol, phenprocoumon)
10) Use of any medications that prolong the QT interval and CYP3A4 inhibitors if the treatment cannot be either safely discontinued or switched to a different medication prior to starting study drug administration. Please see http://www.torsades.org/medicalpros/ drug-lists/printable-drug-list.cfm for a comprehensive list of agents that prolong the QT interval as well as Post-Text Supplement 2.
11) Patients who have undergone major surgery < or equal to 2 weeks prior to Visit 1 or who have not recovered from side effects of such surgery
12) Patients who have received wide field radiotherapy < or equal to 4 weeks or limited field radiation for palliation < 2 weeks prior to Visit 1 or who have not recovered from side effects of such therapy
13) A history of noncompliance to medical regimens or inability or unwillingness to return for scheduled visits
14) Women who are pregnant, breast feeding or adults of reproductive potential not employing an effective method of birth control. Post menopausal women must be amenorrheic for at least 12 months to be considered of non-childbearing potential. Male or female patients must agree to employ an effective method of contraception during the study and for up to three months following discontinuation from the study. Effective methods of contraception are defined as those which result in a low failure rate (i.e. less than 1 % per year) when used consistently and correctly.
15) Patients unwilling or unable to comply with the protocol |