This study aims to elucidate the effects of neoadjuvant Tislelizumab combined with chemotherapy in locally advanced Microsatellite Stable (MSS) colon cancer.
The standard treatment for locally advanced colon cancer is complete mesocolic excision (CME) followed by adjuvant chemotherapy. The MOSAIC and 16968 studies have shown that about 30% of patients experience recurrence and metastasis within 6-7 years after surgery. Neoadjuvant chemotherapy may improve the prognosis of colon cancer patients. The significant tumor remission after neoadjuvant therapy probably indicates a better long-term survival for patients. The OPTICAL and Fluoropyrimidine Oxaliplatin and Targeted Receptor Pre-Operative Therapy (FoxTROT) studies have shown that approximately 35% of patients are resistant to oxaliplatin-containing neoadjuvant chemotherapy, with a pathological complete response (pCR) rate of less than 10% and uncertain survival improvement. Moreover, previous study shown that immunotherapy has unsatisfied efficacy for microsatellite stable (MSS) colon cancer. Therefore, it is necessary to explore more effective neoadjuvant treatment strategy for tumor therapy. Immunogenic cell death will be enhanced by oxaliplatin-induced immunogenicity and combined with anti-programmed cell death 1 (PD-1) monoclonal antibodies for neoadjuvant therapy. The study will conduct 2 or 4 cycles of Tislelizumab with Oxaliplatin and Capecitabine, followed by CME surgery. The study's primary endpoint is the proportion of pCR in the pathological specimens of surgically resected tumors.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
60
200 mg on Day 1 every 3 weeks and repeat for 2 or 4 cycles. The incidence of adverse events with Tislelizumab is relatively low. The Tislelizumab dose adjustment was implemented according to the prescribing information.
Oxaliplatin 130mg/m2 on Day 1 every 3 weeks and repeat for 2 or 4 cycles. The dose reduction protocol for oxaliplatin-induced toxicity was implemented according to the study in British Journal of Cancer (2018) 118:1322-1328.
Oral Capecitabine 1000 mg/m2 twice daily combined with oxaliplatin chemotherapy from Day 1 to Day 14 every 3 weeks and repeat for 2 or 4 cycles. The dose reduction protocol for capecitabine-induced toxicity was implemented according to the study in British Journal of Cancer (2018) 118:1322-1328.
The First Affiliated Hospital of Guangxi Medical University
Nanning, Guangxi, China
pCR
the proportion of tumor regression grades 0 (TRG0, disappearance of tumor cells) in the pathological specimens of surgically resected tumors.
Time frame: 3-5 days of postoperative pathological examination
R0 resection
the rate of a microscopically margin-negative resection, in which no gross or microscopic tumor remains in the primary tumor bed.
Time frame: 3-5 days of postoperative pathological examination
Disease-free survival (DFS)
3-year disease-free survival
Time frame: 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.
Overall survival (OS)
3-year overall survival
Time frame: From the date of the patient signs the informed consent form until the date of the patient's death, assessed up to 36 months.
Adverse events (AEs)
the rate of adverse events
Time frame: up to half a year
Immune-related adverse events (irAEs)
the rate of immune-related adverse events
Time frame: up to half a year
Surgical complication
the rate of surgical complication during or after operation.
Time frame: From the day of surgery to 30 days after the operation, including intraoperative and postoperative complications.
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The specific surgical approach is laparoscopic. The tumor blood supply is ligated and cut at the root of the mesentery, and the margin of resection should be no less than 10cm. Complete resection of the mesocolon (CME) is performed in conjunction.
T lymphocyte
Cells with cellular immune function. The types and counts of T cells are analyzed using flow cytometry.
Time frame: up to 3 months after surgery.
Gene mutation signatures of colon cancer
Next-generation target sequencing is performed to analyze the gene mutation signatures.
Time frame: up to 3 months before surgery