Efficacy and Safety of Dovitinib in Patients With Gastrointestinal Stromal Tumors Refractory and/or Intolerant to Imatinib (MACS1755)

• Progression-free survival (PFS) of patients treated with Dovitinib [ Time Frame: 9 months ] [ Designated as safety issue: No ]
  The PFS duration: time from entry into the study to the date of the first documented progression (assessed using conventional RECIST (version 1.1) or death due to any cause.
• Time to treatment failure (TTF)of patients treated with Dovitinib [ Time Frame: 9 months ] [ Designated as safety issue: No ]
  TTF: the date of entry into the study to the earliest date of the first objective tumor progression, date of death due to any cause, or date of discontinuation due to reasons other than 'Protocol deviation' or 'Administrative problems'.
• Duration of response or stable disease [ Time Frame: 9 months ] [ Designated as safety issue: No ]
  Duration of response or stable disease: time from the date of entry into the study to the earliest date of the first objective tumor progression or death.
• Time to tumor progression (TTP)of patients treated with Dovitinib [ Time Frame: 9 months ] [ Designated as safety issue: No ]
  TTP: time from the date of entry into the study to first documentation of tumor progression or death due to the underlying cancer.
• Overall response rate (ORR)of patients treated with Dovitinib [ Time Frame: Baseline, 12 weeks ] [ Designated as safety issue: No ]
  Outcome Measure Description: ORR: proportion of patients whose best overall response is either complete response (CR) or partial response (PR) according to RECIST (version 1.1).
• Overall survival (OS)of patients treated with Dovitinib [ Time Frame: 21 months (9 months of estimated treatment plus 12 months of survival follow up) ] [ Designated as safety issue: No ]
  Outcome Measure Description: OS: from the date of entry into the study to the date of death due to any cause. A patient who has not died by the date of the analysis cut-off would have the OS censored at the time of the last contact before the cut-off date.

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 800mg/day or patients with unresectable and/or metastatic GIST who are intolerant to 800 mg/day or less of 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.