The Effects of Neoadjuvant Tislelizumab Combined With Chemotherapy in Locally Advanced MSS Rectal Cancer

Phase 2

Recruiting

• Conditions: Rectal Cancer; Rectal Cancer Stage II; Rectal Cancer Stage III
• Interventions: Drug: Tislelizumab combined with chemotherapy

• Registration Number: NCT06254521
• Lead Sponsor: First Affiliated Hospital of Guangxi Medical University

Brief Summary

This study aims to elucidate the effects of neoadjuvant Tislelizumab combined with chemotherapy in locally advanced MSS rectal cancer.

Detailed Description

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 Timeline

• Study First Submitted: 2024-01-01
• Status Verified: 2024-02
• Study First Submitted QC: 2024-02-03
• Last Update Submitted: 2024-02-03
• Study First Posted: 2024-02-12
• Last Update Posted: 2024-02-12
• Study Start: 2024-02-22
• Primary Completion: 2024-12-30
• Study Completion: 2027-12-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 60

Inclusion Criteria

• Age ≥18 years old and ≤70 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 less than 12cm from the anus as measured by colonoscopy and MRI,or TRUS.
• It was confirmed by magnetic resonance imaging (MRI) or intracavitary ultrasound of the rectum as T3-4 or N+, and M0 by enhanced CT.
• The ECOG physical status score is 0-1.
• 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 ≥ 90g/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.

Exclusion Criteria

• Early rectal cancer (T1-2N0M0); The lower margin of the tumor was less than 5cm from the anus and T4. APR(combined abdominal perineal resection) is required;
• Multifocal colorectal cancer.
• 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 COPD, coronary heart disease, and renal insufficiency) and/or severe acute infectious diseases (such as but not limited to hepatitis, pneumonia, and myocarditis), ASA 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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
neoadjuvant Tislelizumab combined with chemotherapy	Tislelizumab combined with chemotherapy	Patients with locally advanced rectal cancer who met the inclusion criteria received two or four cycles of Tislelizumab combined Capecitabine and Oxaliplatin regimen chemotherapy and were evaluated by enhanced CT and MRI\\TRUS. Then, these patients will receive curative surgery for rectal cancer. Interventions: Drug: Oxaliplatin Drug: Capecitabine Drug: Tislelizumab Procedure: curative surgery for rectal cancer

Primary Outcome Measures

Name	Time	Method
Pathological complete response (pCR) rate	7days of postoperative pathological examination	the proportion of tumor regression grades 0 (TRG0, disappearance of tumor cells) in the pathological specimens of surgically resected tumors

Secondary Outcome Measures

Name	Time	Method
3-year disease-free survival(DFS) rate	36 months from date of the patient signs the informed consent form	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.
3-year overall survival(OS) rate	36 months from date of the patient signs the informed consent form	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.
the rate of adverse events(AEs)	From the first day of immunotherapy until 6 months after the end of treatment	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).
the rate of immune-related adverse events(irAEs)	From the first day of immunotherapy until 6 months after the end of treatment	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).
the rate of R0 resection	7 days of postoperative pathological examination	the rate of a microscopically margin-negative resection, in which no gross or microscopic tumor remains in the primary tumor bed
Complete Clinical Response(cCR) rate	5 days before surgery	cCR:After non-surgical antitumor therapy, physical examination and auxiliary examination(CT and MRI ) found no local evidence of tumor residue.
Retain anal proportions	immediately after the surgery	The proportion of cases with anal retention in all patients undergoing surgery
3-year local recurrence rate	36 months from date of the patient signs the informed consent form	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.
the rate of surgical complication during or after operation	From the day of surgery to 30 days after the 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)

Trial Locations

Locations (1)

The First Affiliated Hospital of Guangxi Medical University; 🇨🇳 Nanning, Guangxi, China