Second-line Pharmacotherapy Patterns and Outcomes of Advanced Gastrointestinal Stromal Tumor: a Real-world Study
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 100
- 试验地点
- 8
- 主要终点
- Progression-free survival rate
研究概览
简要总结
This is a prospective, multicenter, observational real-world study to explore the second-line Pharmacotherapy patterns and clinical outcomes in GIST patients who progressed on or were intolerant to first-line anticancer treatment.
详细描述
INTRODUCTION AND RATIONALE Gastrointestinal stromal tumors (GIST) are thought to develop from the interstitial cells of Cajal or their stem cell precursors. They are the most common mesenchymal tumors occurring in the gastrointestinal (GI) tract. The annual incidence of GIST is about 1/100,000 ~ 2/100,000 globally. Previous data showed that the incidence of GIST was 0.43 per 100,000 in Shanxi Province and 2.11per 100,000 in Shanghai in China.
Surgery is the primary therapy for patients with localized resectable disease. GIST that is metastatic or locally advanced but unresectable is treated with tyrosine kinase inhibitors (TKIs) that target KIT or PDGFRA.
Imatinib is recommended as the first-line standard treatment for metastatic or unresectable advanced GIST. Most patients with initial clinical benefits from Imatinib eventually progress. However, approximately 10% -14% of GIST is primarily resistant to imatinib and 90% of patients will develop secondary drug resistance within 4 years with imatinib treatment.
For patients who failed imatinib first-line treatment, Sunitinib is the standard second-line therapy but not the optimal treatment regimen in clinical practice. Other TKIs targeting KIT is also used in the second-line setting. A phase 3 study to evaluate sunitinib's efficacy in advanced GIST compared with placebo, showed that the mPFS was 5.6 months [2], while a phase I study of ripretinib demonstrated that the mPFS was10.7months as a second-line treatment in advanced GIST[4]. Another single-arm second-line treatment study of dasatinib also suggested that dasatinib had a tumor suppression effect in the treatment of advanced GIST with imatinib treatment failure, with mPFS of 2.9 months, and mOS of 19 months, especially for patients with SRC overexpression and PDGFRA D842V mutation [5]. There is a lack of real-world data on advanced GIST patients who have progressed on first-line treatment with different treatment patterns, and the benefits are also unknown.
The investigators initiate this prospective, observational, real-world study that aims to explore the second-line treatment patterns and the clinical outcomes in GIST patients who progressed on or were intolerant to first-line treatment in real-world clinical practice.
研究设计
- 研究类型
- Observational
- 观察模型
- Case Only
- 时间视角
- Prospective
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 who are aged ≥ 18 years.
- •Patients who have histologically confirmed metastatic or unresectable GIST.
- •Patients who received imatinib at a fixed dose or 1 other TKI as prior treatment regimens. Patients who experienced intolerance to prior therapies must have objective disease progression before enrollment.
- •Patients must have at least a measurable lesion according to mRECIST Version 1.
- •According to the current GIST national guidelines, patients who receive second-line treatments, including but not limited to sunitinib, imatinib dose escalation, ripretinib, dasatinib, and other drug treatments.
- •Patients with an Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 to 2 at screening.
排除标准
- •Patients who previously received two or more TKIs as prior treatment regimens.
- •Patients with a life expectancy of fewer than three months.
- •Patients who are pregnant and lactating.
- •Patients with an estimated poor adherence or inability to complete follow-up.
- •Patients who are not appropriate to enroll due to the investigator's consideration.
结局指标
主要结局
Progression-free survival rate
时间窗: 1 year
The primary objective is to demonstrate the proportion of patients with progression-free survival (PFS) determined by radiological assessment per modified Response Evaluation Criteria in Solid Tumors (mRECIST), version 1.1 in patients with advanced GIST following the second-line treatment.
次要结局
- objective response rate (ORR)(2 years)
- Time to objective response(1 year)
- Safety-TEAEs(2 years)
- Progression-free survival(2 years)
- overall survival (OS)(2 years)
- R0/R1 resection rate(2 years)
- EORTC QLQ-C30(Difference between baseline and every 3 month during the follow-up period)
研究者
Xinhua Zhang, MD
First Affiliated Hospital, Sun Yat-Sen University
First Affiliated Hospital, Sun Yat-Sen University