A Single-arm, Open-label, Multicenter Phase 2 Study to Evaluate XELOX + Tislelizumab in Combination With Doxorubicin Hydrochloride Liposome Injection （XELOX+PD-1+PLD）as Neoadjuvant Therapy for Resectable Gastric Cancer
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 38
- 试验地点
- 1
- 主要终点
- Pathological complete remission rate
研究概览
简要总结
This is a signle-arm, multi-center, open-lable, phase II study. The objective is to evaluate the effectiveness and safety of tislelizumab + oxaliplatin + capecitabine + PLD in the neoadjuvant treatment of resectable gastric adenocarcinoma.
详细描述
This single-arm, multicenter, open-label study plan to enroll patients with resectable stage III gastric adenocarcinoma to recieve tislelizumab + oxaliplatin + capecitabine + PLD regimen for 2 or 4 cycles, radical resection will be performed after neoadjuvant therapy. Radiological evaluation will be performed every 2 cycles to evaluate the resectability of tumor. Survival follow-up will be performed after surgery, until patient's withdrawal of informed consent, loss to follow-up or death, whichever comes first.
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
- •Age: 18~75 years old.
- •Karnofsky Performance Status Score ≥
- •Histological or cytological diagnosed as gastric adenocarcinoma, HER2-, PD-1/L1+.
- •Clinical stage stage III (8th edition of the AJCC Cancer Staging Manual).
- •Physical condition and organ function allow for larger abdominal surgery.
- •Subject baseline blood routine and biochemical indicators meet the following standards: hemoglobin ≥90g/L; absolute neutrophil count (ANC) ≥1.5×10^9g/L; platelets counts (PLT) ≥100×10^9/L; alanine aminotransferase (ALT), aspartate aminotransferase (AST) ≤2.5 times the upper limit of normal (ULN); serum total bilirubin <1.5 ULN; serum creatinine <1 ULN; serum albumin ≥30g/L.
- •Heart function:
- •Left ventricular ejection fraction (LVEF) ≥50%;
- •12-ECG indicates no myocardial ischemia;
- •No history of arrhythmia requiring drug intervention before enrollment;
- •No serious concomitant diseases that make the survival time < 5 years.
- •Agree and be able to comply with the protocol during the study period.
- •Provide written informed consent before entering the study.
排除标准
- •Received chemotherapy, radiotherapy or immunotherapy for this gastric cancer.
- •Pregnant or breastfeeding women.
- •Women of childbearing age who had a positive pregnancy test at baseline or who did not have a pregnancy test. Menopausal women must have menopause for at least 12 months before they can become pregnant.
- •Men and women who are sexually active (possible to have children) are unwilling to use contraception during the study period.
- •Patients with mass ascites and positive abdominal free cancer cells.
- •With a history of other malignancies in the last 5 years, except for cured non-melanoma skin cancer and cervical carcinoma in situ.
- •With a history of epilepsy, central nervous system disease, or mental disorder may be judged by the investigator that their clinical severity may hinder the signing of informed consent or affect the patient's oral medication compliance.
- •Clinically severe (i.e. active) heart disease, such as symptomatic coronary heart disease, New York Heart Association (NYHA) grade II or more severe congestive heart failure, or severe arrhythmia requiring medical intervention, or the last 12 There was a history of myocardial infarction within months.
- •Patients deficiency of dihydropyrimidine dehydrogenase (DPD).
- •Peripheral nerve disease ≥ NCI CTC AE grade
- •However, the patients only with deep tendon reflex (DTR) disappears do not need to be excluded.
- •Organ transplantation requires immunosuppressive therapy.
- •Severe uncontrolled repeated infections, or other serious uncontrolled concomitant diseases.
- •Moderate or severe renal damage [creatinine clearance ≤50ml/min (calculated according to Cockroft and Gault equation), or serum creatinine> ULN].
- •Acute or chronic active hepatitis B, hepatitis C infection, hepatitis B virus (HBV) DNA>2000IU/ml or 10^4 copies/ml, hepatitis C virus (HCV) RNA>10^3 copies/ml, hepatitis B surface antigen (HbsAg) is positive at the same time as anti-HCV antibody.
- •Allergic to any research drug ingredients.
- •Participating in other trials within 4 weeks before enrollment.
- •Not suitable to participate in this trial for any reason judged by the investigator.
研究组 & 干预措施
Experiment group
Pegylated Liposomal Doxorubicin + Oxaliplatin + Capecitabine + Tislelizumab; reapt every 21 days.
干预措施: PLD (Drug)
Experiment group
Pegylated Liposomal Doxorubicin + Oxaliplatin + Capecitabine + Tislelizumab; reapt every 21 days.
干预措施: Oxaliplatin (Drug)
Experiment group
Pegylated Liposomal Doxorubicin + Oxaliplatin + Capecitabine + Tislelizumab; reapt every 21 days.
干预措施: Capecitabine (Drug)
Experiment group
Pegylated Liposomal Doxorubicin + Oxaliplatin + Capecitabine + Tislelizumab; reapt every 21 days.
干预措施: Tislelizumab (Drug)
结局指标
主要结局
Pathological complete remission rate
时间窗: 4-month
Completely resected tumor specimens and all sampled regional lymph nodes were detected without residual infiltration (ie ypT0 ypN0 in AJCC staging version 8.0)
次要结局
- Objective response rate(3-month)
- R0 resection rate(4-month)
- Progress-free survival(3-year)
- 3-year PFS rate(3-year)
- 3-year overall survival rate(3-year)
研究者
Qi Li
Chief Physician
Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine