Perioperative Surufatinib Plus Sintilimab Combined With Chemotherapy in Locally Advanced Gastric and Gastroesophageal Junction Adenocarcinoma: the Phase 2 Solids-01 Trial
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- Pathological complete response（pCR）rate
研究概览
简要总结
For locally advanced gastric and gastroesophageal junction adenocarcinoma (cT3-4bNanyM0), perioperative PD-1 antibody combined with chemotherapy can downstage tumor stage, increase the R0 resection rate, and may improve the long-term survival. Combination of perioperative surufatinib, sintilimab and chemotherapy for locally advanced gastric and gastroesophageal junction adenocarcinoma could be a novel therapeutic strategy to increase response rate and therapeutic efficacy. Surufatinib, as the oral drug in this study is a small molecule kinase inhibitor that mainly acts on vascular growth factor receptor (VEGFR1, 2,3), fibroblast growth factor receptor 1(FGFR1) and colony stimulating factor 1 receptor (CSF1R). It is a proprietary product developed by Hutchison Whampoa Pharmaceutical (Shanghai, China) Co., LTD. Surufatinib has been approved for neuroendocrine tumor. This study is a monocenter, single-arm phase 2 clinical trial to evaluate tolerability, safety and efficacy of perioperative surufatinib in combination with sintilimab and chemotherapy in locally advanced gastric and gastroesophageal junction adenocarcinoma.
详细描述
The incidence of gastric and gastroesophageal junction adenocarcinoma is increasing in China, and it is one of the most common malignant tumors in China. Surgery is the only possible way to cure gastric and gastroesophageal junction adenocarcinoma, however, over 70-80% of gastric/gastroesophageal junction adenocarcinoma patients in China are in advanced stage. Locally gastric/gastroesophageal junction adenocarcinoma (cT3-4bNanyM0) could be cured by multi-disciplinary therapies including surgery, immunotherapy and chemotherapy. Perioperative immunotherapy plus chemotherapy can downstage tumor T and N stage, increase the R0 resection rate, and may improve the long-term survival. However, the therapeutic effects still not satisfactory to date. Surufatinib, as the novel oral antivascular targeting drug, has been proved to be effective in neuroendocrine tumor. Combination of perioperative surufatinib and immunotherapy plus chemotherapy for locally advanced gastric/gastroesophageal junction adenocarcinoma could be a novel therapeutic strategy to increase response rate and therapeutic efficacy. This study is a monocenter, single-arm phase 2 clinical trial to evaluate tolerability, safety and efficacy of perioperative surufatinib in combination with sintilimab and chemotherapy in locally advanced gastric and gastroesophageal junction adenocarcinoma.
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
- •signed informed consent
- •patients age 18-75 years;
- •Histologically CT/MRI confirmed cT3-4bNanyM0 gastric or GEJ adenocarcinoma;
- •ECOG 0-1, no surgery contraindications;
- •Expected survival ≥3 months;
排除标准
- •signs of distant metastases
- •Prior chemotherapy, radiotherapy, surgery for gastric cancer;
- •Significant cardiovascular disease
- •major surgical procedure within 4 weeks prior to initiation of study treatment
- •current treatment with anti-viral therapy or HBV
- •pregnancy or breastfeeding
- •history of malignancy within 5 years prior to screening
- •Present or history of any autoimmune disease or immune deficiency;
- •Prior therapy with a PD-1, anti-PD-Ligand 1 (PD-L1) or CTLA-4 agent;
- •There are active gastric and duodenal ulcers, ulcerative colitis and other gastrointestinal diseases, or active bleeding in unresectable tumors.
- •Poorly controlled hypertension or diabetes;
研究组 & 干预措施
Surufatinib，sintilimab and SOX chemotherapy
Surufatinib: 250mg qd，d1-21, q3w; Surufatinib: 200mg, ivdrip, d1, q3w; SOX: Oxaliplatin+S-1 S-1:40~60mg Bid, d1~14, q3w; Oxaliplatin: 130mg/m2, ivdrip,d1, q3w; Neoadjuvant therapy for 2-4 cycles, adjuvant therapy for 3-5 cycles. After 6 cycles of SOX chemotherapy, Surufatinib + Surufatinib was taken orally until one year.
干预措施: Sintilimab (Drug)
Surufatinib，sintilimab and SOX chemotherapy
Surufatinib: 250mg qd，d1-21, q3w; Surufatinib: 200mg, ivdrip, d1, q3w; SOX: Oxaliplatin+S-1 S-1:40~60mg Bid, d1~14, q3w; Oxaliplatin: 130mg/m2, ivdrip,d1, q3w; Neoadjuvant therapy for 2-4 cycles, adjuvant therapy for 3-5 cycles. After 6 cycles of SOX chemotherapy, Surufatinib + Surufatinib was taken orally until one year.
干预措施: Surufatinib (Drug)
Surufatinib，sintilimab and SOX chemotherapy
Surufatinib: 250mg qd，d1-21, q3w; Surufatinib: 200mg, ivdrip, d1, q3w; SOX: Oxaliplatin+S-1 S-1:40~60mg Bid, d1~14, q3w; Oxaliplatin: 130mg/m2, ivdrip,d1, q3w; Neoadjuvant therapy for 2-4 cycles, adjuvant therapy for 3-5 cycles. After 6 cycles of SOX chemotherapy, Surufatinib + Surufatinib was taken orally until one year.
干预措施: S1 (Drug)
Surufatinib，sintilimab and SOX chemotherapy
Surufatinib: 250mg qd，d1-21, q3w; Surufatinib: 200mg, ivdrip, d1, q3w; SOX: Oxaliplatin+S-1 S-1:40~60mg Bid, d1~14, q3w; Oxaliplatin: 130mg/m2, ivdrip,d1, q3w; Neoadjuvant therapy for 2-4 cycles, adjuvant therapy for 3-5 cycles. After 6 cycles of SOX chemotherapy, Surufatinib + Surufatinib was taken orally until one year.
干预措施: Oxaliplatin (Drug)
结局指标
主要结局
Pathological complete response（pCR）rate
时间窗: From the initiation date of first cycle (each cycle is 21 days) to the date of operation, an average of 12 weeks
次要结局
- R0 resection rate(From the initiation date of first cycle (each cycle is 21 days) to the date of operation, an average of 12 weeks.)
- Overall survival (OS)(From the initiation date of first cycle (each cycle is 21 days) to the date of first documented progression or date of death from any cause, whichever came first, assessed up to 3 years)
- Disease free survival (DFS)(From the initiation date of first cycle (each cycle is 21 days) to the date of first documented progression or date of death from any cause, whichever came first, assessed up to 3 years)
- Event free survival (EFS)(From the initiation date of first cycle (each cycle is 21 days) to the date of first documented progression or date of death from any cause, whichever came first, assessed up to 3 years.)
- Overall survival (OS)(From the initiation date of first cycle (each cycle is 21 days) to the date of first documented date of death from any cause, assessed up to 3 years.)