An Open Phase II Clinical Study of Tislelizumab Combined With Lenvatinib and GEMOX Versus Tislelizumab Combined With GEMOX in the Treatment of Locally Advanced Intrahepatic Cholangiocarcinoma and Gallbladder Cancer.
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 60
- 试验地点
- 1
- 主要终点
- Objective response rate (ORR)
研究概览
简要总结
This is an Open Phase II Clinical Study of Tislelizumab Combined with Lenvatinib and GEMOX Versus Tislelizumab Combined with GEMOX in the Treatment of Locally Advanced Intrahepatic Cholangiocarcinoma and Gallbladder Cancer.
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
- None
入排标准
- 年龄范围
- 20 Years 至 79 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •1：Intrahepatic cholangiocarcinoma and gallbladder carcinoma confirmed by histology or cytology.
- •Potential resectable criteria: The first stage R0 resection cannot be guaranteed for patients with cholangiocarcinoma admitted to our hospital, and there are the following imaging characteristics (satisfy one or more)
- •The hilar and retroperitoneal lymph nodes were considered for metastasis but could be resected completely.
- •Intrahepatic cholangiocarcinoma has multiple foci, but foci are less than three and limited to half of the liver.
- •Local progression of gallbladder carcinoma with colon or duodenal involvement.
- •Hilar cholangiocarcinoma or lower segment of cholangiocarcinoma involving portal vein or hepatic artery requires combined vascular resection or reconstruction.
- •Patient age: 20-79 years
- •At least one measurable lesion as defined in RECIST version 1.1
- •ECOG score was 0-1 5.Life expectancy of at least 90 days 6.Aspartic aminotransferase and alanine aminotransferase ≤150 IU/L in patients with bile drainage, and ≤100IU/L in patients without bile drainage Total bilirubin ≤3.0 mg/dL in patients with bile drainage and ≤2.0 mg/dL in patients without bile drainage.
- •7.Creatinine ≤1.5 mg/dL was used in the single treatment cohort and ≤1.2 mg/dL was used in the combination treatment cohort; Creatinine clearance [measured or estimated using the Cockcroft-Gault equation]≥45mL/min for the single treatment cohort and ≥50mL/min for the combination treatment cohort 8.Neutrophil ≥1500 cells /µL, hemoglobin ≥9.0g/dL, platelet ≥100000/µL 9.PD-L1 expression analysis and microsatellite unstable state analysis were performed on tumor tissue samples.
排除标准
- •Previous treatment with tislelizumab or anti-PD-1, PD-L1, PD-L2, CD137, CTLA-4 antibody, or any other therapy that regulates T cells
- •Received systemic corticosteroid or immunosuppressive therapy within 28 days before inclusion
- •Concurrent autoimmune diseases or a history of chronic or recurrent autoimmune diseases
- •A history of pleural adhesions or pericardium adhesions within 28 days prior to inclusion
- •Test positive for HIV antibody, human T-cell leukemia virus type 1 antibody, hepatitis C virus antibody, hepatitis B surface protein antigen, hepatitis B surface protein antibody, hepatitis B core protein antibody or any detectable hepatitis B virus DNA
- •Multiple primary cancers (except completely resected basal cell carcinoma, stage I squamous cell carcinoma, carcinoma in situ, intramucosal carcinoma, and superficial bladder carcinoma, and any other cancer that has not recurred for at least 5 years)
- •Brain or meningeal metastases (unless asymptomatic and do not require treatment)
- •and uncontrolled or severe cardiovascular disease.
研究组 & 干预措施
tislelizumab+lenvatinib+GMOX
tislelizumab 200mg, Q3W, lenvatinib 8mg/kg, PO, qd, gemcitabine 1g/㎡, D1, D8, Q3W, oxaliplatin 100mg/㎡, D1, Q3W. Imaging evaluation was performed after 3 cycles.
Patients who met surgical criteria will receive R0 resection and adjuvant therapy 4-8 weeks after surgery (tislelizumab 200mg, Q3W, lenvatinib 8mg/kg, PO, qd) for one year or until disease progression or toxicity became intolerable.
Inoperable patients continue to receive ≤4 cycles of treatment, imaging evaluation every two cycles. Patients will receive R0 resection if meet surgical criteria and adjuvant therapy 4-8 weeks after surgery (Tislelizumab 200mg, Q3W, lenvatinib 8mg/kg, PO, qd,) for one year or until disease progression or toxicity became intolerable.
Patients still unable to receive surgery, the experimental group will receive tislelizumab 200mg, Q3W, lenvatinib 8mg/kg, PO, qd for maintained treatment until disease progression or toxicity became intolerable.
干预措施: tislelizumab+lenvatinib+GMOX (Drug)
tislelizumab+GEMOX
tislelizumab 200mg, Q3W, gemcitabine 1g/㎡, D1, D8, Q3W, oxaliplatin 100mg/㎡, D1, Q3W. Imaging evaluation was performed after 3 cycles.
Patients who met surgical criteria will receive R0 resection and adjuvant therapy 4-8 weeks after surgery (tislelizumab 200mg, Q3W) for one year or until disease progression or toxicity became intolerable.
Inoperable patients continue to receive ≤4 cycles of treatment, imaging evaluation every two cycles. Patients will receive R0 resection if meet surgical criteria and adjuvant therapy 4-8 weeks after surgery (Tislelizumab 200mg, Q3W) for one year or until disease progression or toxicity became intolerable.
Patients still unable to receive surgery, the experimental group will receive tislelizumab 200mg, Q3W for maintained treatment until disease progression or toxicity became intolerable.
干预措施: tislelizumab+GEMOX (Drug)
结局指标
主要结局
Objective response rate (ORR)
时间窗: 6 months
次要结局
- Progression-free survival (PFS)(18 months)
- R0 resection rate(6 months)
- Overall survival (OS)(24 months)
- AE(24 months)