Prospective, Multicenter, Randomized Trial of Neoadjuvant Capecitabine and Oxaliplatin (CAPOX) Plus Tislelizumab Versus CAPOX in Microsatellite Stable High-risk Locally Advanced Colon Cancer
试验速览
- 阶段
- 3 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 94
- 试验地点
- 1
- 主要终点
- Pathological complete response (pCR)
研究概览
简要总结
Building on earlier exploratory work, this study further designs a multi-institutional, prospective, randomized clinical trial to evaluate the efficacy and safety of the combination therapy of the immune checkpoint inhibitor Tislelizumab with CAPOX for neoadjuvant treatment in high-risk locally advanced MSS-type colorectal cancer, as well as its impact on patient outcomes. This study aims to provide new evidence for the clinical practice of treating MSS-type colorectal cancer.
详细描述
Patients were randomly assigned to either the experimental group, receiving neoadjuvant therapy with Tislelizumab combined with CAPOX, or the control group, receiving neoadjuvant CAPOX chemotherapy alone. Patients in the experimental group underwent four cycles of neoadjuvant CAPOX chemotherapy plus Tislelizumab prior to surgery. Patients in the control group received four cycles of neoadjuvant CAPOX chemotherapy alone. Patients deemed eligible for R0 resection based on radiographic assessment proceeded to radical colorectal cancer surgery. Following surgery, patients in both groups were to complete an additional four cycles of CAPOX chemotherapy. We compared and analyzed the short- and long-term clinical outcomes between the Tislelizumab plus CAPOX regimen and CAPOX alone for the treatment of microsatellite stable (MSS)-type high-risk locally advanced colon cancer (stages T4NanyM0 or TanyN+M0).
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
- 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 years old and ≤75 years old.
- •Pathologically diagnosed MSS ((confirmed by microsatellite stable detection or next-generation target sequencing) or (confirmed by immunohistochemistry)) colon adenocarcinoma.
- •The lower edge of the tumor is more than 12cm from the anus as measured by colonoscopy and the lower edge of the tumor cannot be directly palpated during rectal examination.
- •Enhanced CT stage T4 or T1-4 N+ without multiple primary tumors or distant metastasis.
- •The Eastern Cooperative Oncology Group physical status score is 0-
- •Life expectancy is expected to be more than 1 year.
- •First diagnosis, no previous anti-tumor treatment received, and no chemotherapy contraindications.
- •Appropriate organ function is defined as follows: Hemoglobin level ≥ 60g/L, Neutrophil count ≥ 1.5×10^9/L, Platelet count ≥ 75×10^9/L, Serum total bilirubin ≤ 1.5× the upper limit of normal (UNL), Aspartate aminotransferase (AST) ≤ 2× UNL, Alanine aminotransferase (ALT) ≤ 3× UNL, Serum creatinine ≤ 1.5× UNL.
- •Informed consent, able to understand the study protocol and willing to participate in the study, and will provide written informed consent.
排除标准
- •Enhanced CT stage (T1-3N0M0)
- •Multifocal colorectal cancer.
- •CT or MRI in the mid-sagittal plane shows that the lower border of the tumor is below the line connecting the sacrococcygeal promontory and the upper border of the pubic symphysis.
- •Tumor obstruction or high risk of obstruction, bleeding, and/or perforation requiring emergency surgery or stent placement.
- •Cannot tolerate chemotherapy or immunotherapy, such as but not limited to bone marrow suppression.
- •History of malignant tumors, except for basal cell carcinoma, papillary thyroid carcinoma, and various in situ cancers.
- •Acute exacerbation of important organ diseases (such as but not limited to chronic obstructive pulmonary disease, coronary heart disease, and renal insufficiency) and/or severe acute infectious diseases (such as but not limited to hepatitis, pneumonia, and myocarditis), American Society of Anesthesiologists score > 3 points.
- •Mental disorders, illiteracy, or language communication barriers that prevent the understanding of the study protocol.
- •Peripheral sensory neuropathy, unable to receive oxaliplatin-based chemotherapy.
- •Continuous use of glucocorticoids for more than 3 days within 1 month prior to signing the informed consent form, or having comorbidities requiring the use of glucocorticoid therapy.
- •Unable to undergo enhanced CT examination
- •Pregnancy or lactation.
- •Refused to participate in this study.
- •Other situations in which the researcher deems unsuitable for this study.
研究组 & 干预措施
CAPOX chemotherapy
Patients in the experimental group underwent two or four cycles of preoperative CAPOX combined with placebo. Patients assessed as suitable for R0 resection by imaging underwent radical colectomy. Following surgery, all patients in both groups completed an additional four or six cycles of adjuvant CAPOX chemotherapy.
干预措施: Oxaliplatin (Drug)
CAPOX combined with Tislelizumab
Patients in the experimental group underwent two or four cycles of preoperative CAPOX combined with Tislelizumab. Patients assessed as suitable for R0 resection by imaging underwent radical colectomy. Following surgery, all patients in both groups completed an additional four or six cycles of adjuvant CAPOX chemotherapy.
干预措施: Tislelizumab (Drug)
CAPOX combined with Tislelizumab
Patients in the experimental group underwent two or four cycles of preoperative CAPOX combined with Tislelizumab. Patients assessed as suitable for R0 resection by imaging underwent radical colectomy. Following surgery, all patients in both groups completed an additional four or six cycles of adjuvant CAPOX chemotherapy.
干预措施: Oxaliplatin (Drug)
CAPOX combined with Tislelizumab
Patients in the experimental group underwent two or four cycles of preoperative CAPOX combined with Tislelizumab. Patients assessed as suitable for R0 resection by imaging underwent radical colectomy. Following surgery, all patients in both groups completed an additional four or six cycles of adjuvant CAPOX chemotherapy.
干预措施: Capecitabine (Drug)
CAPOX chemotherapy
Patients in the experimental group underwent two or four cycles of preoperative CAPOX combined with placebo. Patients assessed as suitable for R0 resection by imaging underwent radical colectomy. Following surgery, all patients in both groups completed an additional four or six cycles of adjuvant CAPOX chemotherapy.
干预措施: Capecitabine (Drug)
结局指标
主要结局
Pathological complete response (pCR)
时间窗: 3-5 days of postoperative pathological examination
the proportion of tumor regression grades 0 (TRG0, disappearance of tumor cells) in the pathological specimens of surgically resected tumors.
次要结局
- R0 resection(3-5 days of postoperative pathological examination)
- Overall survival (OS)(From the date of the patient signs the informed consent form until the date of the patient's death, assessed up to 36 months.)
- Disease-free survival (DFS)(From date of the patient signs the informed consent form until the date of earliest occurrence of the patient's tumor recurrence or death, whichever came first, assessed up to 36 months.)
- Adverse events (AEs)(up to half a year)
- Surgical complication(From the day of surgery to 30 days after the operation, including intraoperative and postoperative complications.)
- Immune-related adverse events (irAEs)(up to half a year)