Inclusion Criteria:

• histologically or cytologically confirmed GIST.
• advanced/metastatic GIST.
• experienced failure of prior treatment with imatinib 600-800 mg per day defined by progression of disease according to RECIST criteria during treatment. Radiographic evidence of PD on imatinib must be confirmed by the Investigator prior to enrollment.
• May have focal progression of disease including a new enhancing nodular focus within a pre-existing tumor nodule; such a nodule should be considered measurable by standard RECIST criteria.
• measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as >20 mm with conventional techniques or as >10 mm with spiral CT scan.
• At least 4 weeks since prior therapy with imatinib & resolution of all acute toxic effects of the prior therapy or surgical procedure to grade ≤1.
• Age >18 years.
• ECOG performance status 0-2.

• Normal organ and marrow function as defined below:

  • ANC >1,500/mcL
  • Platelets >100,000/mcL
  • Total bilirubin < or equal to 1.5 X ULN
  • AST(SGOT)/ALT(SGPT) < or equal to 2.5 X ULN OR < or equal to 5.0 X ULN if considered due to tumor
  • Amylase/Lipase < or equal to 1.5 X ULN
  • Alkaline Phosphatase < or equal to 2.5 X ULN or </= 5 X ULN if considered tumor related.
  • Potassium, magnesium, calcium, phosphorus, creatinine WNL prior to randomization
  • OR
  • Creatinine clearance of > 50 calculated by cockroft-gault formula
• WOCBP must have negative pregnancy test within 7 days of first treatment and use appropriate contraception.
• Ability to understand and willingness to sign a written informed consent document.

Exclusion Criteria:

• Have received nilotinib or additional tyrosine kinase inhibitors or additional targeted therapies (except for imatinib).
• May not be receiving any other investigational agents within 4 weeks before treatment.
• Prior or concomitant malignancies (with a relapse in the last 5 years or requiring active treatment) other than GIST and with exception of previous or concomitant basal cell skin, previous cervical carcinoma in situ.
• Impaired cardiac function, including any one of the following:

Complete left bundle branch block. Ventricular paced cardiac pacemaker. Congenital long QT syndrome or family history of long QT syndrome. History of or presence of symptomatic ventricular or atrial tachyarrhythmias. Clinically significant resting bradycardia (< 50 beats per minute). QTc > 480 msec on screening ECG (using the QTcF formula). If QTc > 480 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 diseases (e.g., unstable angina, congestive heart failure or uncontrolled hypertension).

Severe and/or uncontrolled concurrent medical disease that could cause unacceptable safety risks or compromise compliance with protocol e.g. impairment of GI function, or GI disease that may significantly alter absorption of study drugs; uncontrolled diabetes; active infections; psychiatric illness/social situation that would limit compliance with study requirements.

• Inability to remain laying down in PET scanner for up to one hour.
• Use of any medications that prolong the QT interval and CYP3A4 inhibitors if treatment cannot be either safely discontinued or switched to a different medication prior to starting study drug administration.
• Major surgery ≤ 2 weeks prior to Visit 1 or who have not recovered from side effects of such surgery.
• Known history of noncompliance to medical regimens or inability/unwillingness to return for scheduled visits, patients who are pregnant or breast feeding, patients unwilling or unable to comply with the requirements for the protocol.
• Known chronic liver disease (i.e., chronic active, hepatitis, and cirrhosis).
• Known diagnosis of HIV, currently taking combination antiretroviral therapy.