A Prospective, Double Blind, Randomized, Placebo-Controlled Phase III Trial of Imatinib Re-Challenge in Patients With Gastrointestinal Stromal Tumor Who Had Benefit From Prior Imatinib But Progression From Both Imatinib and Sunitinib
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 81
- 试验地点
- 1
- 主要终点
- Progression-free Survival
研究概览
简要总结
The objective of this study is to compare the clinical outcomes following resumption of dosing (re-challenge) with Imatinib plus best supportive care versus placebo plus best supportive care in patients with advanced/incurable Gastrointestinal Stromal Tumors following failure of prior imatinib and sunitinib therapies.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Investigator, Outcomes Assessor)
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
- •Patients aged 18 years and older
- •Patients with metastatic or unresectable malignant gastrointestinal stromal tumour which has been histologically confirmed by the detection of CD117 on immunohistochemical staining or genetically confirmed by the detection of mutation in KIT or PDGFRα genes on direct sequencing of tumor DNA.
- •Prior benefit from 1st line imatinib defined as complete response, partial response, or stable disease at 6 months after the start of 1st line imatinib
- •Patients whose disease has progressed despite at least both prior imatinib therapy (400mg/day) and then subsequently also failure of prior sunitinib therapy.
- •ECOG(Eastern Cooperative Oncology Group) performance status 0 ~ 3
- •Adequate bone marrow function as defined by platelets ≥ 75 x 109/L and neutrophils ≥ 1.5 x 109/L
- •Adequate renal function, with serum creatinine < 1.5 x upper limit of normal
- •Adequate hepatic function with serum total bilirubin < 1.5 x upper limit of normal, alanine aminotransferase or aspartate aminotransferase < 2.5 x upper limit of normal in the absence of liver metastases, or < 5 x upper limit of normal in the presence of liver metastases.
- •Expected life expectancy of greater than 12 weeks in the absence of any intervention
- •No other malignant disease apart from non-melanotic skin cancer or carcinoma in situ of the uterine cervix or any other cancer except where treated with curative intent > 5 years previously without evidence of relapse
- •Written, informed consent to the study
排除标准
- •Medical or psychiatric conditions that compromise the patient's ability to give informed consent or to complete the protocol or a history of non- compliance
- •Last dose of radiotherapy received within 4 weeks before the start of study treatment, excluding palliative radiotherapy
- •Obstruction of gastrointestinal tract
- •Active gastrointestinal bleeding
- •Myocardial infarction within 6 months prior to the study medication, and other clinically significant heart disease (e.g., unstable angina, congestive heart failure or uncontrolled hypertension)
- •Evidence of severe or uncontrolled systemic disease or any concurrent condition which in the investigator's opinion makes it undesirable for the patient to participate in the study or which would jeopardise compliance with the protocol
- •Female patients who are pregnant or breast-feeding. Female patients must have had a negative pregnancy test within one week before starting imatinib.
研究组 & 干预措施
Imatinib
Patients will be randomly assigned to receive imatinib at a dose of 400mg/day, taken once daily with food, in the form of 100-mg tablets. The study medication will be administered until disease progression, unacceptable toxicity, or withdrawal of consent.
干预措施: Imatinib (Drug)
Placebo
Patients will be randomly assigned to receive placebo at a dose of 400mg/day, taken once daily with food, in the form of 100-mg tablets. The study medication will be administered until disease progression or withdrawal of consent.
干预措施: Placebo (Drug)
结局指标
主要结局
Progression-free Survival
时间窗: up tp12 weeks
To compare the progression free survival (PFS) assessed by the blinded independent central review following resumption of dosing (re-challenge) with Imatinib plus best supportive care versus placebo plus best supportive care in patients with unresectable or metastatic GIST following failure of at least prior imatinib and sunitinib therapies
次要结局
- Disease Control Rate(up to 12 weeks)
- Progression Free Survival(up to 12 weeks)
- Response Rate(Up to 12weeks)
- Overall Survival(OS) and Time to Progression(TTP)(Up to 3years)
- Safety and Tolerability of Imatinib(Up to 3years)
研究者
Yoon-Koo Kang
Study Principal Investigator
Asan Medical Center