A randomized, open-label, multi-center phase III study to evaluate the efficacy and safety of nilotinib versus imatinib in adult patients with unresectable or metastatic gastrointestinal stromal tumors (GIST). - N/A

INTERVENTION: Trade Name: Tasigna Product Name: Nilotinib Product Code: AMN107 Pharmaceutical Form: Capsule, hard INN or Proposed INN: Nilotinib Current Sponsor code: AMN107 Other descriptive name: Tasigna Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 200‐ Trade Name: Glivec Product Name: Imatinib Product Code: STI571 Pharmaceutical Form: Tablet INN or Proposed INN: Imatinib Current Sponsor code: STI571 Other descriptive name: Glivec/ Gleevec Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 100‐ Trade Name: Glivec Product Name: Imatinib Product Code: STI571 Pharmaceutical Form: Tablet INN or Proposed INN: Imatinib Current Sponsor code: STI571 Other descriptive name: Glivec/ Gleevec Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 400‐ CONDITION: adult patients with histologically confirmed unresectable or metastatic GIST, either who have not received prior therapy with TKIs or, who experienced recurrence of GIST > 6 months after stopping adjuvant treatment with imatinib. ; MedDRA version: 9.1 Level: LLT Classification code 10062427 Term: Gastrointestinal stromal tumor PRIMARY OUTCOME: Main Objective: To compare progression free survival (PFS) of nilotinib and imatinib when used as initial therapy of unresectable and/or metastatic GIST in patients either who have not received prior therapy with TKIs or who have recurrent GIST after stopping adjuvant treatment with imatinib. Primary end point(s): Progression free survival (PFS) Secondary Objective: The first three objectives listed below are considered to be the key secondary objectives :; 1. To compare the disease control rate (DCR, defined as the proportion of patients with a best overall response of complete response, partial response, or stable disease which lasted at least 24 weeks) of nilotinib and imatinib in the same patient population.; 2. To compare the time to treatment failure (TTF) of nilotinib and imatinib. ; 3. To compare overall survival (OS) of nilotinib and imatinib.; 4. To compare time to progression (TTP), response rate (RR), time to tumor response, and assess duration of response of nilotinib and imatinib (RECIST criteria). ; 5. To compare the safety and tolerability of nilotinib and imatinib.; 6. To evaluate inter‐ and intra‐patient variability in nilotinib and imatinib exposure over time, and to explore any relationship between the pharmacokinetic exposure of nilotinib or imatinib and clinical responses; INCLUSION CRITERIA: • Age = 18 years • At least one measurable site of disease on CT/MRI scan as defined by RECIST criteria (refer to Post‐text supplement 2) based on investigator’s assessment • Histologically confirmed diagnosis of GIST which is unresectable and/or metastatic and either: o have not received prior therapy with imatinib or any investigational therapies (for example sunitinib or any other TKIs). Note: newly diagnosed patients may have received up to 14 days imatinib treatment for disease management while awaiting study start. o have recurrent GIST = 6 months after stopping adjuvant treatment with imatinib and have subsequently not received any other investigational therapies (for example sunitinib or any other TKIs). For patients with recurrent GIST after stopping adjuvant imatinib two CT scans will be required prior to study entry: one demonstrating absence of disease following completion of adjuvant imatinib and another demonstrating recurrence of