This study aims to elucidate the effects of neoadjuvant Tislelizumab combined with chemotherapy in locally advanced MSS rectal cancer.
The standard treatment for locally advanced rectal cancer is neoadjuvant chemoradiotherapy followed by total mesorectal excision (TME). Pelvic chemoradiotherapy for locally advanced rectal cancer reduces the risk of disease recurrence in the pelvis to less than 10% and has been standard care in North America since 1990.However, it is associated with short-term and long-term toxic effects that can adversely affect quality of life and physical function. 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 TME surgery. This 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
Drug: Oxaliplatin Oxaliplatin 130mg/m2 for chemotherapy 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 report in BJC (2018) 118:1322-1328. Drug: Capecitabine 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 report in BJC (2018) 118:1322-1328. Drug: Anti-PD-1 Monoclonal Antibody 200 mg on Day 1 every 3 weeks and repeat for 2 or 4 cycles. The incidence of adverse events with Anti-PD-1 Monoclonal Antibodies is relatively low. The PD-1 monoclonal antibody (Tislelizumab) dose adjustment was implemented according to the prescribing information. Other Names: Tislelizumab Procedure: Colectomy The specific surgical approach, whether it be laparoscopic
The First Affiliated Hospital of Guangxi Medical University
Nanning, Guangxi, China
RECRUITINGPathological complete response (pCR) rate
the proportion of tumor regression grades 0 (TRG0, disappearance of tumor cells) in the pathological specimens of surgically resected tumors
Time frame: 7days of postoperative pathological examination
Complete Clinical Response(cCR) rate
cCR:After non-surgical antitumor therapy, physical examination and auxiliary examination(CT and MRI ) found no local evidence of tumor residue.
Time frame: 5 days before surgery
3-year disease-free survival(DFS) rate
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.CT, MRI and colonoscopy were used to evaluate tumor recurrence.
Time frame: 36 months from date of the patient signs the informed consent form
3-year overall survival(OS) rate
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.
Time frame: 36 months from date of the patient signs the informed consent form
the rate of adverse events(AEs)
Adverse events (NCI CTC AE 5.0) that occurred from the first day of chemotherapy to one day of treatment end (up to half a year).
Time frame: From the first day of immunotherapy until 6 months after the end of treatment
the rate of immune-related adverse events(irAEs)
Immune-related adverse events (NCCN irAEs (2021)) that occurred from the first day of immunotherapy to one day of treatment end (up to half a year).
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Time frame: From the first day of immunotherapy until 6 months after the end of treatment
the rate of 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: 7 days of postoperative pathological examination
the rate of surgical complication during or after operation
From the day of surgery to 30 days after the operation, including intraoperative and postoperative complications(bleeding,anastomotic fistula,intestinal obstruction,Anastomotic stenosis,Surgical site infection(SSI),urinary retention,sexual dysfunction)
Time frame: From the day of surgery to 30 days after the operation
Retain anal proportions
The proportion of cases with anal retention in all patients undergoing surgery
Time frame: immediately after the surgery
3-year local recurrence rate
From the date of the patient signs the informed consent form until the date of the local recurrence, assessed up to 36 months. CT, MRI and colonoscopy were used to evaluate local recurrence.
Time frame: 36 months from date of the patient signs the informed consent form