Neoadjuvant Tislelizumab With Chemotherapy for the Treatment of MSS Colon Cancer

Colonic Neoplasms Clinical Trial

Official title:

Neoadjuvant Tislelizumab With Oxaliplatin and Capecitabine in Microsatellite Stable, Locally Advanced Colon Cancer: A Prospective, Single-arm, Single-center, Exploratory Phase II Clinical Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06124378
• Other study ID #: Minglin Lin
• Status: Recruiting
• Phase: Phase 2
• Start date: November 13, 2023
• Est. completion date: November 30, 2026

Study information

• Verified date: November 2023
• Source: First Affiliated Hospital of Guangxi Medical University
• Contact: Minglin Lin
• Phone: +86-771-5356529
• Email: linminglin[@]sr.gxmu.edu.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study aims to elucidate the effects of neoadjuvant Tislelizumab combined with chemotherapy in locally advanced Microsatellite Stable (MSS) colon cancer.

Description:

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 60
• Est. completion date: November 30, 2026
• Est. primary completion date: November 30, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

• 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 0-1.
• 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:

• 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.

Related Conditions & MeSH terms

• Colonic Neoplasms
• Immune Checkpoint Inhibitors
• Neoadjuvant Therapy

Intervention

Drug:
• Tislelizumab
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
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.
• 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 study in British Journal of Cancer (2018) 118:1322-1328.

Procedure:
• Colectomy
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.

Locations

Country	Name	City	State
China	The First Affiliated Hospital of Guangxi Medical University	Nanning	Guangxi

Sponsors (1)

Lead Sponsor	Collaborator
First Affiliated Hospital of Guangxi Medical University

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	pCR	the proportion of tumor regression grades 0 (TRG0, disappearance of tumor cells) in the pathological specimens of surgically resected tumors.	3-5 days of postoperative pathological examination
Secondary	R0 resection	the rate of a microscopically margin-negative resection, in which no gross or microscopic tumor remains in the primary tumor bed.	3-5 days of postoperative pathological examination
Secondary	Disease-free survival (DFS)	3-year disease-free survival	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.
Secondary	Overall survival (OS)	3-year overall survival	From the date of the patient signs the informed consent form until the date of the patient's death, assessed up to 36 months.
Secondary	Adverse events (AEs)	the rate of adverse events	up to half a year
Secondary	Immune-related adverse events (irAEs)	the rate of immune-related adverse events	up to half a year
Secondary	Surgical complication	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.
Secondary	T lymphocyte	Cells with cellular immune function. The types and counts of T cells are analyzed using flow cytometry.	up to 3 months after surgery.
Secondary	Gene mutation signatures of colon cancer	Next-generation target sequencing is performed to analyze the gene mutation signatures.	up to 3 months before surgery