The study will investigate the comparative efficacy and safety of two oral inhibitors of Kit and PDGFR: nilotinib 400 mg bid, a novel agent, and imatinib 400 mg bid, an approved agent with an established efficacy.

• Drug: Nilotinib
  800mg per day throughout the study
  Other Name: Tasigna
• Drug: Imatinib
  800mg per day throughout the study

• Nilotinib: Experimental
  Intervention: Drug: Nilotinib
• Imatinib: Active Comparator
  Intervention: Drug: Imatinib

Inclusion Criteria:

• Providing a written informed consent.
• Male or female patients ≥ 18 years of age at Visit 1;
• Histologically confirmed diagnosis of GIST of any anatomical location, which is unresectable and/ or metastatic prior to or at Visit 1;
• Positive immunohistochemical staining for c-Kit (CD117) or Kit negative,
• Documented disease progression according to RECIST on prior therapy with imatinib, 400 mg PO qd;

Exclusion Criteria:

• Prior use of imatinib doses higher than 400 mg qd or prior use of any other tyrosine-kinase inhibitor;
• 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 therapy.
• Concomitant antineoplastic treatments, such as chemotherapy, immunotherapy, biological response modifiers, or radiotherapy;
• Lesions that have been irradiated cannot be included as sites of measurable disease. If the only measurable lesion was previously irradiated, the patient cannot be included;
• Serious uncontrolled concomitant medical or psychiatric illness;