A Phase I-II Trial of Dovitinib Plus Docetaxel as Second-line Chemotherapy in Patients With Metastatic or Unresectable Gastric Cancer After Failure of First-line Chemotherapy
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 14
- 试验地点
- 1
- 主要终点
- Progression-free survival
研究概览
简要总结
Docetaxel is currently one of standard second-line therapy in patients with gastric cancer. As angiogenesis and FGFR pathway has been suggested to be associated with gastric cancer, dovitinib, dual VEGFR and FGFR inhibitor, may have the potential to improve the outcomes of patients with gastric cancer. Therefore, we investigated the combination regimen of docetaxel and dovitinib.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 74 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
Dovitinib plus docetaxel
In phase I portion of the study Docetaxel 45-75 mg/m2, intravenous, every 3 weeks Dovitinib 200-500 mg, oral, 5 days on/2 days off
In phase II portion of the study Recommended dose of docetaxel and dovitinib in phase I portion will be used.
干预措施: Dovitinib and docetaxel (Drug)
结局指标
主要结局
Progression-free survival
时间窗: 2 year
Progression-free survival is defined as the time from the first treatment to the onset of progressive disease or to the date of death whichever comes first.
Maximum tolerated dose
时间窗: 6 months
If dose limiting toxicities are experienced in two or more out of six patients in the cohort (more than 33% of patient cohort), that dose will be defined as the maximum tolerated dose.
次要结局
- Response rate(2 year)
- Toxicity(2 years)
- Overall survival(2 years)
- Biomarker(Baseline and 2 weeks after study treatment)
研究者
Yoon-Koo Kang
Professor
Asan Medical Center