Efficacy and Safety of Conversion Therapy With Sintilimab in Combination With Chemotherapy and Apatinib in Patients With Stage IV Gastric Cancer
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 47
- 试验地点
- 1
- 主要终点
- R0-surgery conversion rate
研究概览
简要总结
This is a single-arm, phase II study aiming to evaluate the feasibility and efficacy of sintilimab (PD-1 inhibitor) in combination of apatinib and two-drug chemotherapy (S-1 plus nab-paclitaxel) as conversion therapy in patients with stage IV gastric cancer in China.
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 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •gastric adenocarcinoma confirmed by gastroscopy and pathology (histologically/cytologically ) ;
- •life expectancy of ≥3-month；
- •unresectable patients who were initially diagnosed as stage IV (clinical stage, American Joint Committee on Cancer 8th edition);
- •Eastern Cooperative Oncology Group performance status: 0-1;
- •must have at least 1 of the following unresectable factors indicated by CT, MRI or positron emission tomography(PET)-CT:
- •N3 lymphatic metastasis;
- •Extensive or bulky lymph nodes;
- •Hepatic metastasis: ≤5 lesions, total diameter of ≤8cm;
- •Peritoneal metastasis (CY1, P1);
- •Kukernburg tumor;
- •adequate organ function;
- •pregnant test negative of females of childbearing potential , and willing to use adequate contraception;
- •written Informed Consensus Form;
排除标准
- •prior use of any checkpoint inhibitor treatment, including PD-1, programmed cell death ligand-1(PDL-1), CTLA4 etc;
- •Her-2 positive with willing to use herceptin treatment;
- •prior active autoimmune disease or history of autoimmune disease;
- •clinically significant cardiovascular and cerebrovascular diseases, including but not limited to severe acute myocardial infarction within 6 months before enrollment, unstable or severe angina, or coronary artery bypass surgery, Congestive heart failure (New York heart association (NYHA) class > 2), ventricular arrhythmia which need medical intervention, left ventricular ejection fraction(LVEF) < 50%;
- •not controlled hypertension;
- •prior systemic treatment to metastatic disease；
- •previous digestive tract bleeding history within 3 months or evident gastrointestinal bleeding tendency;
- •history of immunodeficiency including seropositivity for human immunodeficiency virus (HIV), or other acquired or congenital immune-deficient disease, or active hepatitis ;
- •patients who may receive vaccination during study period;
- •mental disorders history, or psychotropic drug abuse history;
- •unable to orally administration;
研究组 & 干预措施
treatment
Eligible patients will be given sintilimab(200mg iv, day 1), apatinib(250mg,once daily), S-1 (60mg, twice daily, day1-14) and nab-paclitaxel(without peritoneal metastases: 260 mg/m^2 iv for 3h; with peritoneal metastases: 200mg/m^2 iv plus 60mg/m^2 ip; day 1) every 3 weeks for at least 3 cycles.
The feasibility of surgery will be evaluated by a multidisciplinary team every 2-4 cycles.
Patients assessed as inoperable will be allowed to continue maintenance therapy with the original regimen until disease progression or intolerable toxicity. For patients assessed as operable, apatinib will be discontinued and one more cycle of sintilimab combined with S-1 and nab-paclitaxel will be administered; radical surgery will be performed within 2-4 weeks after the end of treatment.
Safety run-in stage will be set in the first 6 patients to determine the safety. The study will be terminated if dose-limiting toxicities (DLTs) occur in more than 2 patients.
干预措施: sintilimab (Drug)
treatment
Eligible patients will be given sintilimab(200mg iv, day 1), apatinib(250mg,once daily), S-1 (60mg, twice daily, day1-14) and nab-paclitaxel(without peritoneal metastases: 260 mg/m^2 iv for 3h; with peritoneal metastases: 200mg/m^2 iv plus 60mg/m^2 ip; day 1) every 3 weeks for at least 3 cycles.
The feasibility of surgery will be evaluated by a multidisciplinary team every 2-4 cycles.
Patients assessed as inoperable will be allowed to continue maintenance therapy with the original regimen until disease progression or intolerable toxicity. For patients assessed as operable, apatinib will be discontinued and one more cycle of sintilimab combined with S-1 and nab-paclitaxel will be administered; radical surgery will be performed within 2-4 weeks after the end of treatment.
Safety run-in stage will be set in the first 6 patients to determine the safety. The study will be terminated if dose-limiting toxicities (DLTs) occur in more than 2 patients.
干预措施: apatinib (Drug)
treatment
Eligible patients will be given sintilimab(200mg iv, day 1), apatinib(250mg,once daily), S-1 (60mg, twice daily, day1-14) and nab-paclitaxel(without peritoneal metastases: 260 mg/m^2 iv for 3h; with peritoneal metastases: 200mg/m^2 iv plus 60mg/m^2 ip; day 1) every 3 weeks for at least 3 cycles.
The feasibility of surgery will be evaluated by a multidisciplinary team every 2-4 cycles.
Patients assessed as inoperable will be allowed to continue maintenance therapy with the original regimen until disease progression or intolerable toxicity. For patients assessed as operable, apatinib will be discontinued and one more cycle of sintilimab combined with S-1 and nab-paclitaxel will be administered; radical surgery will be performed within 2-4 weeks after the end of treatment.
Safety run-in stage will be set in the first 6 patients to determine the safety. The study will be terminated if dose-limiting toxicities (DLTs) occur in more than 2 patients.
干预措施: S1 (Drug)
treatment
Eligible patients will be given sintilimab(200mg iv, day 1), apatinib(250mg,once daily), S-1 (60mg, twice daily, day1-14) and nab-paclitaxel(without peritoneal metastases: 260 mg/m^2 iv for 3h; with peritoneal metastases: 200mg/m^2 iv plus 60mg/m^2 ip; day 1) every 3 weeks for at least 3 cycles.
The feasibility of surgery will be evaluated by a multidisciplinary team every 2-4 cycles.
Patients assessed as inoperable will be allowed to continue maintenance therapy with the original regimen until disease progression or intolerable toxicity. For patients assessed as operable, apatinib will be discontinued and one more cycle of sintilimab combined with S-1 and nab-paclitaxel will be administered; radical surgery will be performed within 2-4 weeks after the end of treatment.
Safety run-in stage will be set in the first 6 patients to determine the safety. The study will be terminated if dose-limiting toxicities (DLTs) occur in more than 2 patients.
干预措施: Nab paclitaxel (Drug)
结局指标
主要结局
R0-surgery conversion rate
时间窗: up to one year
The proportion of participants who underwent R0 surgery among all participants.
次要结局
- objective response rate (ORR)(up to one year)
- overall survival (OS)(up to two years)
- disease control rate (DCR)(up to one year)
- event-free survival (EFS)(up to two years)
- conversion rate(up to one year)
- Treatment-Related Adverse Events (TRAEs)(from the first day of treatment until 1 month after the end of treatment)
- surgery-related complications(from the day of surgery to 30 days postoperatively)