Efficacy and Safety of Dovitinib in Patients With Gastrointestinal Stromal Tumors Refractory and/or Intolerant to Imatinib
Condition: Gastrointestinal Stromal Tumors
MeSH terms: Gastrointestinal Stromal Tumors
Intervention: Dovitinib (TKI258)
Intervention description: Oral Dovitinib (TKI258) as a gelatin capsule of 100 mg strength and dosed on a flat scale of 500 mg on a 5 days on /2 days off dosing schedule.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 39.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: GIST; Dovitinib

Summary:

      The purpose of this study is to evaluate the efficacy and safety of Dovitinib in patients
      with gastrointestinal stromal tumors refractory and/or intolerant to Imatinib
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histologically confirmed GIST of any anatomical location, which is 1) unresectable
             and/ or metastatic with documented disease progression while on therapy with imatinib
             or 2) surgically removed localized GIST, recurrent on adjuvant imatinib or recurrent
             within the first 3 months after discontinuation of adjuvant imatinib or 3) patients
             with unresectable and/or metastatic GIST intolerant to imatinib

          -  Positive immunohistochemical staining for c-KIT (CD117); or negative staining for KIT,
             but with either positive staining for DOG1 or an identified mutation of KIT or PDGFRA
             gene

          -  Documented disease progression according to RECIST (version 1.1) on prior therapy with
             imatinib at a dose of at least 400mg/day or patients with unresectable and/or
             metastatic GIST who are intolerant to imatinib

          -  At least one measurable GIST lesion according to RECIST (version 1.1).

          -  Adequate bone marrow, liver and renal function

        Exclusion Criteria:

          -  Patients who have received any other tyrosine-kinase inhibitor but imatinib for GIST

          -  Patients who received cytotoxic drugs ≤ 4 weeks prior to starting Dovitinib (TKI258)

          -  Patients who are treated or planned to be treated concomitantly with other cytotoxic
             or antineoplastic treatments, such as chemotherapy, immunotherapy, biological response
             modifiers, or radiotherapy

          -  Patients with another primary malignancy within 3 years prior to starting the study
             drug

          -  Patients who have undergone major surgery (e.g. intra-thoracic, intra-abdominal or
             intra-pelvic) ≤ 4 weeks prior to starting Dovitinib (TKI258) or who have not recovered
             from the adverse effects of such therapy

          -  Patients with a history of pulmonary embolism (PE), or untreated deep venous
             thrombosis (DVT) within the past 6 months

          -  Patients with impaired cardiac function or clinically significant cardiac diseases

          -  Patients with impairment of gastrointestinal (GI) function or GI disease that may
             significantly alter the absorption of Dovitinib

          -  Patients with prior complete gastrectomy

          -  Patients with brain metastasis or history of brain metastasis

          -  Patients who are currently receiving anticoagulation treatment with therapeutic doses
             of warfarin or equivalent anticoagulant

          -  Pregnant or breast-feeding women

        Other protocol-defined inclusion/exclusion criteria may apply.