Efficacy and Safety of Nilotinib (AMN107) Compared With Current Treatment Options in Patients With GIST Who Have Failed Both Imatinib and Sunitinib
Condition: Gastrointestinal Stromal Tumors
MeSH terms: Gastrointestinal Stromal Tumors
Intervention: Nilotinib; Best Supportive Care (BSC) +/- imatinib or sunitinib
Intervention description: Nilotinib 400 mg twice daily (bid); Can include pain medication, localized radiotherapy, nutritional support, and/or oxygen therapy and blood transfusions. Imatinib or sunitinib can be administered at the last tolerated dose and regimen or at the Investigator's choice.
Intervention MeSH terms: Sunitinib; Imatinib Mesylate
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 248.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: GIST; adults; imatinib resistant; sunitinib resistant; AMN107; nilotinib; treatment; Gastrointestinal stromal tumor (GIST)

Summary:

      The study evaluated the safety and efficacy of nilotinib versus current treatment in adults
      with gastrointestinal stromal tumors (GIST) who have either progressed or who were intolerant
      to the first and second line treatments.
    

Eligibility criteria:

        Inclusion criteria (Core Phase):

          -  Age ≥18 years

          -  Radiological confirmation of disease progression during imatinib and sunitinib therapy
             OR intolerance to imatinib and/or sunitinib

          -  At least one measurable site of disease on CT/MRI scan

          -  Physically fit even if not able to work

          -  Normal organ, electrolyte, and bone marrow function

        Inclusion criteria (Extension Phase):

          -  Patients whose tumors had progressed on the control arm and had crossed over to the
             nilotinib arm.

          -  The study was stopped due to meeting the primary efficacy endpoint of PFS at the
             interim analysis.

          -  Patients who were still being treated at the close of the Core study on the control
             arm or nilotinib arm (whose tumors have not progressed at the time of the end of the
             Core study).

          -  Patients must have had documented, confirmed stable, partial or complete response as
             defined by the RECIST criteria at the time of entry into the Extension study with the
             exception of patients who had progressed on the control arm.

        Exclusion criteria (Core Phase):

          -  Previous treatment with nilotinib or any other drug in this class or other targeted
             therapy

          -  Treatment with any cytotoxic and/or investigational cytotoxic drug ≤ 4 weeks prior to
             study entry

          -  Impaired cardiac function

          -  Use of coumarin derivatives (i.e. warfarin, acenocoumarol, phenprocoumon)

          -  Women who are pregnant or lactating

        Exclusion criteria (Extension Phase):

          -  Use of other anticancer treatments or investigational drugs (with exception of the
             study drugs)

          -  Patients with a history of noncompliance with study drug treatment in the Core study
             protocol.

        Other protocol-defined inclusion/exclusion criteria applied