Evaluation of the Efficacy and Safety of Bevacizumab Combined With PD-1 Monoclonal Antibody in Preoperative Neoadjuvant Therapy for MSS Colorectal Cancer With Liver Metastases - a Single-center, Single-arm, Open-label Clinical Trail
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 入组人数
- 50
- 主要终点
- cCR
研究概览
简要总结
Evaluation of the Efficacy and Safety of Bevacizumab Combined With PD-1 Monoclonal Antibody in Preoperative Neoadjuvant Therapy for MSS Colorectal Cancer With Liver Metastases - a Single-center, Single-arm, Open-label Clinical Trail.
详细描述
In the 2023 Global Cancer Statistics, colorectal cancer remains the third leading cause of cancer-related death in the world. According to the latest China Cancer report, colorectal cancer is the fourth leading cause of cancer-related death in China. More specifically, the incidence and the mortality of colorectal cancer have been increasing year over year. Among newly diagnosed colorectal cancer patients, 20% have distant metastases. The 5-year survival rate for metastatic colorectal cancer (mCRC) is less than 20%. In the latest updated 2023 National Cancer Comprehensive Network (NCCN) Colon Cancer Guidelines, mismatch repair genes/micro satellite state officially became a global classification standard. Patients diagnosed with colorectal cancer must be classified into MSS or MSI-H before treatment, that is, patients are divided into pMMR/MSS and dMMR/MSI-H subtypes after initial examination or clinical management, and then the treatment plan is determined. MSI-H accounts for 15% of all colorectal cancers and is mostly present in patients with early stage tumors. For patients with metastatic colorectal cancer, MSI-H colorectal cancer accounts for only 5% of all patients. Among them, the treatment of immune checkpoint inhibitors in MSI-H patients has become a first-line and neoadjuvant metastatic disease treatment recommendation.
Although clinical trials on the combination of targeted therapy and immunotherapy are increasing, clinical researches and clinical trials of targeted therapy combined immunotherapy, such as bevacizumab combined with PD-1, have not received enough attention and recognition. Currently reports believed that anti-programmed death-1 (PD-1) antibodies have been shown to produce significantly longer progression-free survival with fewer adverse events compared to chemotherapy as a first-line treatment for dMMR metastatic CRC (mCRC). In the simultaneous CRT sequential PD-1 (long range) and TNT simultaneous combined PD-1 (long range) clinical trials, CRT combined with PD-1/PD-L1 showed better near-term efficacy gains (pCR) in patients with locally staged pMMR. Although current researches on neoadjuvant therapy for MSS type bowel cancer is increasingly abundant, especially PD-1 is becoming more and more popular in the treatment of MSS type bowel cancer, the research in the field of neoadjuvant therapy for MSS metastatic colorectal cancer is still not explored. Therefore, our PD-1 combined with bevacizumab in the treatment of MSS type metastatic bowel cancer has greatly research value.
Based on the above reasons, we designed this study to observe the efficacy and safety of the target-free combination therapy regimen of PD-1 combined with bevacizumab for patients with MSS metastatic colorectal cancer, and strive to provide a high-level evidence-based basis for neoadjuvant therapy regimen for patients with MSS metastatic colorectal cancer.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Retrospective
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
- •Men and women aged 18-75 years old;
- •Histologically or radiographically proven colon or rectal adenocarcinoma with liver metastases；
- •ECOG performance status score of 0 to 2；
- •Clinical staged any T with liver metastases (M+);
- •MSS status;
- •Adequate haematological, hepatic, and renal function: neutrophil count ≥1.5×109 /L; platelet count ≥75×109 /L; serum total bilirubin ≤1.5×upper normal limits (UNL); aspartate aminotransferase ≤2.5×UNL; alanine aminotransferase ≤2.5×UNL; serum creatinine ≤1.5 x UNL.
排除标准
- •MSI status;
- •Colorectal cancer without liver metastases;
- •Relapsed colorectal cancer;
- •Complicated with active bleeding, perforation, or requiring emergency surgery;
- •Previous systemic anticancer therapy for colorectal cancer disease;
- •Any active or history of autoimmune disease, or history of syndrome that required systemic steroids or immunosuppressive medications;
- •Patients with other active concurrent non-colorectal cancer;
- •Patients with interstitial lung disease, non-infectious pneumonia or uncontrollable systemic diseases (such as: diabetes, hypertension, pulmonary fibrosis and acute pneumonia);
- •Patients with any Grade 2 or above toxicity as classified by the common terminology criteria for adverse events (CTCAE) (version 5.0) (except for anemia, alopecia and skin pigmentation) which is induced by previous treatment and has not subside;
- •Previously received anti-programmed death-1 (PD-1) or its ligand (PD-L1) antibody, anti- cytotoxic T lymphocyte-associated antigen 4 (cytotoxic T-lymphocyte-associated Protein 4, CTLA-4) antibody Women in pregnancy or lactation;
- •Known positive history or positive test for Human Immunodeficiency Virus or Acquired Immunodeficiency Syndrome (AIDS);
- •History of known or suspected allergies to any related drugs used in the trial; Women who are pregnant or nursing.
研究组 & 干预措施
Bevacizumab Combined With PD-1 Monoclonal Antibody in Preoperative Neoadjuvant Therapy
干预措施: Bevacizumab Combined With PD-1 Monoclonal Antibody (Drug)
结局指标
主要结局
cCR
时间窗: 20 weeks
To evaluate whether neoadjuvant Bevacizumab Combined With PD-1 Monoclonal Antibody would significantly improve the Clinical complete response (cCR) proportion in MSS Colorectal Cancer With Liver Metastases
次要结局
- R0 resection rate(1 day)
- pCR proportion(20 weeks)
- Major pathological response (MPR)(20 weeks)
- Disease-free survival (DFS) and overall survival (OS)(5 years)