Conversion Therapy of Sintilimab Combined With Bevacizumab and XELOX/SOX for Initially Unresectable AFP-positive Gastric/Esophagogastric Junction Adenocarcinoma : A Multi-center, Single-arm, Phase II Trial (SOLIDS-02)
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 入组人数
- 46
- 主要终点
- Objective response rate(ORR)
研究概览
简要总结
Alpha-fetoprotein-producing gastric cancer (AFP-positive gastric cancer, AFP-GC), a rare and highly aggressive subtype of gastric cancer, accounts for 1.3% to 15% of all gastric cancer cases. Its clinical features are significantly different from those of common gastric cancer. Not only does it show abnormally elevated serum AFP levels, but it also has a stronger angiogenic ability, a higher rate of distant metastasis, and a poorer prognosis even after a upfront R0 surgery, making it a challenging problem in the field of gastric cancer treatment. Notably, patients with AFP-positive gastric cancer have a relatively low sensitivity to the traditional standard regimens. There is an urgent need to explore targeted treatment strategies to break through the efficacy bottleneck.
Combination of sintilimab, bevacizumab and XELOX/SOX for initially unresectable AFP-positive gastric/esophagogastric junction adenocarcinoma could be a novel therapeutic strategy to increase response rate and therapeutic efficacy. This study is a multi-center, single-arm phase 2 clinical trial to evaluate efficacy, tolerability and safety of perioperative sintilimab in combination with bevacizumab and XELOX/SOX in initially unresectable AFP-positive gastric/esophagogastric 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 cT3-4N+M0/1 gastric or GEJ adenocarcinoma; (M1 only includes type I liver metastasis of gastric cancer, according to the "Chinese Expert Consensus on Liver Metastasis of Gastric Cancer");
- •Serum AFP levels > 2× upper limit of normal or AFP-positive by IHC staining;
- •Adequate organ function
- •ECOG 0-1, no surgery contraindications;
- •Expected survival ≥3 months;
排除标准
- •HER2-positive status: IHC 3+, or IHC 2+/FISH+
- •Prior chemotherapy, radiotherapy, anti-PD-1/PD-L1 therapy, surgery for gastric cancer;
- •Signs of other distant metastases (e.g., peritoneal, lung, bone, supraclavicular lymph, etc.)
- •Significant cardiovascular disease
- •-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;
- •There are active gastric and duodenal ulcers, ulcerative colitis and other gastrointestinal diseases, or active bleeding in unresectable tumors.
研究组 & 干预措施
Sintilimab, bevacizumab and chemotherapy (XELOX/SOX)
Sintilimab: 200mg, ivdrip, d1, q3w; Bevacizumab:7.5mg/kg，iv drip，d1, q3w; XELOX:Oxaliplatin+ Capecitabine Capecitabine: 1000mg/m2 twice daily, d1-14, q3w Oxaliplatin: 130mg/m2, ivdrip,d1, q3w; SOX: Oxaliplatin+S-1 S-1:40~60mg Bid, d1~14, q3w Oxaliplatin: 130mg/m2, ivdrip,d1, q3w;
干预措施: S-1 (Drug)
Sintilimab, bevacizumab and chemotherapy (XELOX/SOX)
Sintilimab: 200mg, ivdrip, d1, q3w; Bevacizumab:7.5mg/kg，iv drip，d1, q3w; XELOX:Oxaliplatin+ Capecitabine Capecitabine: 1000mg/m2 twice daily, d1-14, q3w Oxaliplatin: 130mg/m2, ivdrip,d1, q3w; SOX: Oxaliplatin+S-1 S-1:40~60mg Bid, d1~14, q3w Oxaliplatin: 130mg/m2, ivdrip,d1, q3w;
干预措施: Oxaliplatin (Drug)
Sintilimab, bevacizumab and chemotherapy (XELOX/SOX)
Sintilimab: 200mg, ivdrip, d1, q3w; Bevacizumab:7.5mg/kg，iv drip，d1, q3w; XELOX:Oxaliplatin+ Capecitabine Capecitabine: 1000mg/m2 twice daily, d1-14, q3w Oxaliplatin: 130mg/m2, ivdrip,d1, q3w; SOX: Oxaliplatin+S-1 S-1:40~60mg Bid, d1~14, q3w Oxaliplatin: 130mg/m2, ivdrip,d1, q3w;
干预措施: Capecitabine (Drug)
Sintilimab, bevacizumab and chemotherapy (XELOX/SOX)
Sintilimab: 200mg, ivdrip, d1, q3w; Bevacizumab:7.5mg/kg，iv drip，d1, q3w; XELOX:Oxaliplatin+ Capecitabine Capecitabine: 1000mg/m2 twice daily, d1-14, q3w Oxaliplatin: 130mg/m2, ivdrip,d1, q3w; SOX: Oxaliplatin+S-1 S-1:40~60mg Bid, d1~14, q3w Oxaliplatin: 130mg/m2, ivdrip,d1, q3w;
干预措施: Bevacizumab (Drug)
Sintilimab, bevacizumab and chemotherapy (XELOX/SOX)
Sintilimab: 200mg, ivdrip, d1, q3w; Bevacizumab:7.5mg/kg，iv drip，d1, q3w; XELOX:Oxaliplatin+ Capecitabine Capecitabine: 1000mg/m2 twice daily, d1-14, q3w Oxaliplatin: 130mg/m2, ivdrip,d1, q3w; SOX: Oxaliplatin+S-1 S-1:40~60mg Bid, d1~14, q3w Oxaliplatin: 130mg/m2, ivdrip,d1, q3w;
干预措施: Sintilimab (Drug)
结局指标
主要结局
Objective response rate(ORR)
时间窗: From first dose to end of study treatment or last tumor assessment prior to conversion surgery or disease progression.Up to 24 weeks.
Objective response rate(ORR):CR+PR
次要结局
- R0 resection rate(From the initiation date of first cycle (each cycle is 21 days) to the date of operation.Up to 24 weeks.)
- Major pathological response rate(From the initiation date of first cycle (each cycle is 21 days) to the date of operation.Up to 24 weeks.)
- One year progression-free survival (PFS)(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 1 year.)
- One year overall survival(OS)(The Kaplan-Meier survival from the initiation date of first cycle until death from any cause or the last follow-up date,assessed up to 1 year.)