Efficacy and Safety of Dovitinib in Patients With Gastrointestinal Stromal Tumors Refractory and/or Intolerant to Imatinib

DOVIGIST: Phase II Trial to Evaluate the Efficacy and Safety of Dovitinib (TKI258) in Patients With Gastrointestinal Stromal Tumors Refractory and/or Intolerant to Imatinib

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

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.