Clinical Efficacy of Albumin Paclitaxel Plus Carrelizumab Versus FLOT in Neoadjuvant Treatment of Locally Advanced Gastric Cancer With Different Immunotypes--A Multi-center, Randomised, Open, Phase 3 Clinical Trial
试验速览
- 阶段
- 3 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 216
- 试验地点
- 2
- 主要终点
- Objective response rate
研究概览
简要总结
To evaluate the clinical efficacy of albumin paclitaxel combined with carelizumab and FLOT in the neoadjuvant treatment of locally advanced gastric cancer with different immune types
详细描述
Background: At present, there is still a lack of prospective data to systematically compare the clinical efficacy of different neoadjuvant therapies in patients with different genotypes. To explore the clinical efficacy and safety of albumin paclitaxel combined with carrelizumab compared with FLOT neoadjuvant therapy in patients with locally advanced gastric cancer of different immune types.
Methods: This study is a multi center prospective study. 216 patients with gastric adenocarcinoma were included in the study to explore the proportion of PD-L1 positive cells in tumor tissue, evaluate the expression of PD-L1, serum HBV DNA level or other biomarkers.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
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 from 18 to 75 years, all sex；
- •Primary gastric adenocarcinoma (papillary, tubular, mucinous, signet ring cell, or poorly differentiated) confirmed pathologically by histology or cytology；
- •CT/MRI,PET-CT or laparoscopic exploration were used to confirm the diagnosis of gastric cancer staging as cT2-4a and/or N+ and M0 before operation.；
- •Measurable lesions at least should be detected by CT/MRI examination in accordance with the RECIST1.1.（CT scan of tumor lesion length≥10mm，CT scan short diameter of lymph node≥15mm，scan slice thickness 5mm）;
- •ECOG(Eastern Cooperative Oncology Group) PS(Performance Status):0-1 scores;
- •The expected survival time is more than 12 weeks;
- •The main organ function is normal, which should meet the following criteria:
- •blood routine examination standards should be met（no blood transfusion within 14 days）
- •WBC≥3×109/L
- •ANC≥1.5×109/L，
- •PLT≥100×109/L；
- •biochemical examination shall comply with the following criteria：
- •BIL <1.5normal upper limit（ULN），
- •ALT 和 AST<2.5ULN，GPT≤1.5×ULN；
- •serum Cr≤1ULN，creatinine clearance rate>60ml/min（Cockcroft-Gault formula）
- •women of childbearing age must have a pregnancy test in 7 days before entering the group (in serum), and the results were negative, and willing to use appropriate contraception during the study period and the last 8 weeks after giving drug; men should have the surgical sterilization, or adopt the appropriate contraceptive methods during the test and the last 8 weeks after giving drug.；
- •No other clinical studies were conducted before and during the treatment； participants is willing to participate in this study, sign the informed consent, have good compliance, cooperate with follow-up.
排除标准
- •Previous history of chemotherapy, radiotherapy, targeted drug therapy or immunotherapy
- •Patients with contraindications for surgical treatment and chemotherapy or whose physical condition and organ function do not allow for major abdominal surgery；
- •Patients with metastasis；
- •Having any active autoimmune diseases or a history of autoimmune diseases (such as interstitial pneumonia, uveitis, enteritis, hepatitis, pituitary inflammation, vasculitis, myocarditis, nephritis, hyperthyroidism, hypothyroidism, including but not limited to these diseases or syndromes); Patients with vitiligo or cured childhood asthma/allergies who did not need any intervention in adulthood were excluded; Autoimmune hypothyroidism treated with a stable dose of thyroid replacement hormone; Type 1 diabetes with stable doses of insulin；
- •A history of immunodeficiency, including HIV testing positive, or other acquired or congenital immunodeficiency disorders, or a history of organ transplantation and allogeneic bone marrow transplantation；
- •Accompanied by serious heart, lung, liver, kidney disease; Have nerve, mental disease; Jaundice or obstruction of the digestive tract with severe infection；
- •Pregnant or lactating women；
- •The blood pressure of patients with hypertension cannot be reduced to the normal range by the antihypertensive drugs (systolic pressure >140 mmHg, diastolic pressure >90 mmHg)；
- •With Ⅰ magnitude of coronary heart disease, arrhythmia (including QTc protracted between male > 450 ms, women > 470 ms) and cardiac insufficiency；
- •Patients have a clear tendency with gastrointestinal bleeding, including the following situation: local active ulcerative lesions, and fecal occult blood (+ +); with melena and hematemesis history in 2 months; and patients with fecal occult blood (+) and coagulation dysfunction (INR(international normalized ratio)>1.5, APTT(activated partial thromboplastin time)>1.5 ULN), with bleeding tendency;；
- •Subjects have failed to control good cardiovascular clinical symptoms or disease, including but not limited to: such as: (1) the NYHA class II heart failure or above (2) unstable angina pectoris (3) MI occurred within 1 year (4) have clinical significance of supraventricular or ventricular arrhythmias without clinical intervention on or after clinical intervention is still poorly controlled；
- •History of interstitial lung disease (except radiation pneumonia without hormone therapy), and history of non-infectious pneumonia；
- •Patients are positive of urine protein (urine protein detection 2+ or above, or 24 hours urine protein quantitative >1.0g)；
- •A person who has previously been allergic to any component of the drug in this study； The researchers consider those who were not suitable for inclusion.
研究组 & 干预措施
Immune activated experimental group
Albumin paclitaxel 260mg/m2, ivgtt, d1, d8 Carrelizumab: 200mg, ivgtt, d1, q3w
干预措施: Camrelizumab (Drug)
Immune activated experimental group
Albumin paclitaxel 260mg/m2, ivgtt, d1, d8 Carrelizumab: 200mg, ivgtt, d1, q3w
干预措施: Albumin Taxol (Drug)
Immune activated control group
Docetaxel 50mg/m2, ivgtt, d1, q14d; Oxaliplatin 85mg/m2, ivgtt, d1, q14d; Calcium folinate 200mg/m2, ivgtt, d1, q14d; 5-fluorouracil 2600mg/m2, 24h civ, d1, q14d
干预措施: FLOT scheme (Drug)
Immune silence experimental group
Carrelizumab: 200mg, ivgtt, d1, q3w Docetaxel 50mg/m2, ivgtt, d1, q14d; Oxaliplatin 85mg/m2, ivgtt, d1, q14d; Calcium folinate 200mg/m2, ivgtt, d1, q14d; 5-fluorouracil 2600mg/m2, 24h civ, d1, q14d
干预措施: Camrelizumab (Drug)
Immune silence experimental group
Carrelizumab: 200mg, ivgtt, d1, q3w Docetaxel 50mg/m2, ivgtt, d1, q14d; Oxaliplatin 85mg/m2, ivgtt, d1, q14d; Calcium folinate 200mg/m2, ivgtt, d1, q14d; 5-fluorouracil 2600mg/m2, 24h civ, d1, q14d
干预措施: FLOT scheme (Drug)
Immunosilent control group
Docetaxel 50mg/m2, ivgtt, d1, q14d; Oxaliplatin 85mg/m2, ivgtt, d1, q14d; Calcium folinate 200mg/m2, ivgtt, d1, q14d; 5-fluorouracil 2600mg/m2, 24h civ, d1, q14d
干预措施: FLOT scheme (Drug)
结局指标
主要结局
Objective response rate
时间窗: 4 months
Objective response rate (ORR) according to Response Evaluation Criteria in Solid Tumours (RECIST) version. 1.1, and immune-related (ir) RECIST
次要结局
- Duration of postoperative hospital stay(30 days)
- Disease control rate(4 months)
- 1-year and 3-year OS(1 and 3 years)
- 1-year and 3-year DFS(1 and 3 years)
- The prediction performance of Exosome contents (including proteins, nucleic acids)(3 years)
- R0 resection rate(4 months)
- Adverse event(3 years)
- Overall postoperative morbidity rates(30 days)
- 30 days mortality rates(30 days)
研究者
Chang-Ming Huang, Prof.
Director of gastric surgery
Fujian Medical University