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

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

NCT ID: NCT06254521

Condition: Rectal Cancer
Rectal Cancer Stage II
Rectal Cancer Stage III

Conditions: Official terms:
Rectal Neoplasms
Tislelizumab

Conditions: Keywords:
locally advanced rectal cancer
neoadjuvant
PD-1

Study type: Interventional

Study phase: Phase 2

Overall status: Recruiting

Study design:

Allocation: N/A

Intervention model: Single Group Assignment

Intervention model description: 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 purpose: Treatment

Masking: None (Open Label)

Intervention:

Intervention type: Drug
Intervention name: Tislelizumab combined with chemotherapy
Description: 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
Arm group label: neoadjuvant Tislelizumab combined with chemotherapy

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.

Criteria for eligibility:
Criteria:
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.

Gender: All

Minimum age: 18 Years

Maximum age: N/A

Healthy volunteers: No

Locations:

Facility:
Name: The First Affiliated Hospital of Guangxi Medical University

Address:
City: Nanning
Zip: 530021
Country: China

Status: Recruiting

Contact:
Last name: Sen Zhang, Professor

Phone: 13407738560
Email: zs0771@126.com

Start date: February 22, 2024

Completion date: December 30, 2027

Lead sponsor:
Agency: First Affiliated Hospital of Guangxi Medical University
Agency class: Other

Source: First Affiliated Hospital of Guangxi Medical University

Record processing date: ClinicalTrials.gov processed this data on November 12, 2024

Source: ClinicalTrials.gov page: https://clinicaltrials.gov/ct2/show/NCT06254521