Dovitinib Plus Docetaxel in Gastric Cancer

Inclusion criteria

• Pathologically proven metastatic or unresectable adenocarcinoma of stomach or gastroesophageal junction
• Patients with progressive disease (radiological confirmation required) after one line of chemotherapy except taxane for advanced gastric cancer in palliative setting
• Presence of at least one evaluable disease by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
• Age of 18 to 74 years
• Estimated life expectancy of more than 3 months
• Eastern Cooperative Oncology Group (ECOG) performance status 0~2
• Adequate bone marrow function (Absolute neutrophil counts ≥ 1,500/uL, hemoglobin ≥ 8.0g/dL, and platelet ≥ 100,000/uL)
• Adequate renal function (creatinine < 1.5mg/dL)
• Adequate hepatic function (total bilirubin < 1.5 mg/dL, transaminase < 3 times the upper normal limit [5 times for patients with liver metastasis])
• No prior anti-angiogenic therapy (anti-VEGF or VEGFR tyrosine kinase inhibitor etc) or FGF/FGFR inhibitor
• No prior radiation therapy within 4 weeks of the study (Irradiated lesions should not be included in the evaluable lesions.)
• Written informed consent

Exclusion criteria

• Past or concurrent history of neoplasm other than gastric adenocarcinoma, except for curatively treated non-melanoma skin cancer or in situ carcinoma of the cervix uteri
• Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to study treatment start
• Bowel obstruction
• Evidence of serious gastrointestinal bleeding
• Presence of central nervous system (CNS) metastasis
• History of significant neurologic or psychiatric disorders
• Significant cardiac disease within 6 months of the study (congestive heart failure uncontrollable by medication, symptomatic coronary heart disease, or arrhythmia, myocardial infarction)
• Left ventricular ejection fraction (LVEF) assessed by 2-D echocardiogram (ECHO) or multiple gated acquisition scan (MUGA), < 45%
• Uncontrolled hypertension defined by a SBP ≥ 160 mm Hg and/or DBP ≥ 100 mm Hg, with or without anti-hypertensive medication. Initiation or adjustment of antihypertensive medication (s) is allowed prior to study entry.
• QTc > 480 msec on screening ECG
• Proteinuria defined by NCI CTCAE grade > 1 at baseline as measured by a urine dipstick (2+ or greater) and confirmed by a 24 hour urine collection ( > 1g/24hrs). Subjects may be re-screened if blood pressure is shown to be controlled with or without intervention
• History of thrombotic or bleeding diathesis or coagulopathy
• Serious non-healing wound, peptic ulcer, or bone fracture
• Abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months
• Pregnant or lactating women, women of childbearing potential not employing adequate contraception
• Other serious illness or medical conditions