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
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 39
- 试验地点
- 1
- 主要终点
- Antitumor Activity of Dovitinib in Terms of Disease Control Rate (DCR): Complete Response+Partial Response +Stable Disease
研究概览
简要总结
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
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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.
研究组 & 干预措施
Dovitinib (TKI258)
Patients will receive Dovitinib (TKI258) on an outpatient basis at the dose of 500 mg qd for 5 days followed by 2 days off, every week for cycle of 4 weeks (28d) until disease progression, unacceptable toxicity, or consent withdrawal.
干预措施: Dovitinib (TKI258) (Drug)
结局指标
主要结局
Antitumor Activity of Dovitinib in Terms of Disease Control Rate (DCR): Complete Response+Partial Response +Stable Disease
时间窗: 12 Weeks
DCR is defined as the proportion of patients with a best overall response of Complete Responses (CR), Partial Response (PR) and Stable Disease (SD) at 12 weeks according to RECIST (version 1.1). Complete Response (CR): Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to \< 10 mm 1;Partial Response (PR): At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. Progressive Disease (PD): At least a 20% increase in the sum of diameter of all measured target lesions, taking as reference the smallest sum of diameter of all target lesions recorded at or after baseline. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm2. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for PD.
次要结局
- Time to Treatment Failure (TTF)of Patients Treated With Dovitinib(9 months)
- Progression-free Survival (PFS) of Patients Treated With Dovitinib(9 months)
- Overall Response Rate (ORR) of Patients Treated With Dovitinib(Baseline, 12 weeks)
- Overall Survival (OS) of Patients Treated With Dovitinib(21 months (9 months of estimated treatment plus 12 months of survival follow up))
- Time to Tumor Progression (TTP)of Patients Treated With Dovitinib(9 months)
- DCR (CR+PR+SD) at the End of Treatment(Up to 9 months of estimated treatment)
- Duration of Response or Stable Disease (SD)(9 months)