PD1 Antibody Combined With mFOLFOX6 Neoadjuvant Therapy for Advanced Resectable Metastatic Colon Cancer，Single Arm, Multicenter Phase II Clinical Study
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 入组人数
- 23
- 主要终点
- pathologic complete response（pCR）
研究概览
简要总结
Evaluate the efficacy and safety of PD1 monoclonal antibody combined with mFOLFOX6 neoadjuvant therapy for advanced resectable metastatic colon cancer with enriched pro-inflammatory pan macrophage subpopulations
详细描述
In this study, patients with advanced resectable metastatic colon cancer requiring neoadjuvant chemotherapy were selected, and colon cancer patients enriched with TNFSF10+CXCL10+ panTAMs subgroup were screened, and neoadjuvant chemotherapy was performed with PD-1 monoclonal antibody combined with chemotherapy. To evaluate the efficacy and safety of PD-1 monoclonal antibody combined with neoadjuvant chemotherapy in the treatment of special types of colon cancer.
All patients in this study were examined in the tumor microenvironment before treatment, and only patients enriched with TNFSF10+CXCL10+ panTAMs subgroup were enrolled in the study. Due to the long detection time, the patient received mFOLFOX6 chemotherapy for one week in the first cycle. If the test results meet the enriched proinflammatory panmacrophage subpopulation, patients can eventually be enrolled and receive PD-1 monoclonal antibody (Serplulimab, Srulimab) combined with mFOLFOX6 (oxaliplatin, fluorouracil) regimen, 2 weeks for 1 cycle. The primary radical resection was performed after 5 cycles of neoadjuvant therapy. Local treatment of liver/lung metastases was performed at the same time or at different times. Continue mFOLFOX6 chemotherapy for 4-6 cycles or CAPEOX regimen for 4 cycles within 1-2 months after surgery. Liver and lung metastases allow local treatment in any of these treatment cycles, including but not limited to radiofrequency ablation, particle implantation, radiation therapy, and surgery. At the end of postoperative adjuvant therapy, NED status was achieved. Then, regular follow-up.
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 the inform consent
- •Age >=18 years old, female and male
- •Locally advanced or metastatic colorectal adenocarcinoma (including sig-ring cell carcinoma, mucinous adenocarcinoma, etc.) confirmed by pathology (histology or cytology)
- •Enriched with proinflammatory panmacrophage subsets
- •At least one measurable or evaluable lesion according to RECIST 1.1; Measurable lesions should not have received local treatment such as radiotherapy (Metastases can still be used as target lesions to evaluate efficacy after biopsy. Periintestinal lymph node imaging determines metastasis, allowing for a minimum diameter of ≥ 10mm, and can also be used as target lesions.)
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1
- •The life expectancy is ≥6 months；And according to the MDT in the hospital, only neoadjuvant chemotherapy is needed
- •Hemoglobin content (HB) ≥ 90g/L; Absolute neutrophil count (ANC) ≥ 1.5 × 109/L;Platelet count (PLT) ≥ 100 × 109/L (did not use interleukin-11 or TPO within 14 days);White blood cell count (WBC) ≥ 4.0 × 109/L (no use of granulocyte stimulating factor within 14 days).
- •Total serum bilirubin (TBIL) ≤ 1.5 times the upper limit of normal value (ULN); ALT and AST ≤ 2.5 × ULN;Cr ≤ 1.5 × ULN or creatinine clearance rate (CCr) ≥ 60ml/min, (Cockcroft Gault formula);Serum albumin ≥ 25 g/L (2.5 g/dL)
- •For liver metastasis subjects, AST and ALT must be ≤ 5 x ULN, and white blood cells must be ≥ 4 × 109/L, platelets without blood transfusion ≥ 100 × 109/L, absolute neutrophil count (ANC) ≥ 1.5 without granulocyte stimulating factor treatment × 109/L, hemoglobin ≥ 90 g/L
- •Doppler ultrasound evaluation: Left ventricular ejection fraction (LVEF) ≥ lower limit of normal value (50%).
- •Adequate coagulation function, defined as international standardized ratio (INR) or prothrombin time (PT) ≤ 1.5 times ULN;
排除标准
- •Allergy to any investigational drug or its excipients, or a history of severe allergies, or contraindications to investigational drugs;
- •Having a history of autoimmune diseases or being in an active phase;
- •Symptomatic/Asymptomatic Brain Metastasis
- •CT indicates clear ulcerative lesions or fecal occult blood positive for three or more consecutive times, and clinical considerations suggest the presence of gastrointestinal bleeding
- •Abnormal thyroid function or taking thyroxine tablets
- •Previously received allogeneic bone marrow transplantation or organ transplantation;
- •Congenital pulmonary fibrosis, drug-induced pneumonia, organized pneumonia, or CT confirmed active pneumonia;
- •HIV positive, active hepatitis B or C, active pulmonary tuberculosis;
研究组 & 干预措施
Serplulimab, mFOLFOX6
Serplulimab，200mg，iv，q2w，d1； mFOLFOX6（Oxaliplatin: 85 mg/m2，LV ：400mg/m2，Fluorouracil： 400mg/m2 d1，2400 mg/m2 continuous intravenous drip for 46-48 hours；q2w）
干预措施: Serplulimab, mFOLFOX6 (Drug)
结局指标
主要结局
pathologic complete response（pCR）
时间窗: 1 month after resection
pCR is defined as the percentage of participants in the analysis population who have a pathologic complete response
次要结局
- Objective response rate (ORR)(1 month after resection)
- Incidence of Treatment-Emergent Adverse Events(up to 6 months)
- 2-year overall survival rate(2-year)