Neoadjuvant CAPOX Plus Tislelizumab vs CAPOX in MSS High-Risk Locally Advanced Colon Cancer

First Affiliated Hospital of Guangxi Medical University

Status and phase: Begins enrollment in 1 month; Phase 3

Conditions: Immune Checkpoint Inhibitors; Colonic Neoplasms; Neoadjuvant Therapy

Treatments: Drug: Capecitabine; Drug: Tislelizumab; Drug: Oxaliplatin

Study type: Interventional

Funder types: Other

Identifiers

NCT07132008

2025-K0173

Details and patient eligibility

About

Building on earlier exploratory work, this study further designs a multi-institutional, prospective, randomized clinical trial to evaluate the efficacy and safety of the combination therapy of the immune checkpoint inhibitor Tislelizumab with CAPOX for neoadjuvant treatment in high-risk locally advanced MSS-type colorectal cancer, as well as its impact on patient outcomes. This study aims to provide new evidence for the clinical practice of treating MSS-type colorectal cancer.

Full description

Patients were randomly assigned to either the experimental group, receiving neoadjuvant therapy with Tislelizumab combined with CAPOX, or the control group, receiving neoadjuvant CAPOX chemotherapy alone. Patients in the experimental group underwent four cycles of neoadjuvant CAPOX chemotherapy plus Tislelizumab prior to surgery. Patients in the control group received four cycles of neoadjuvant CAPOX chemotherapy alone. Patients deemed eligible for R0 resection based on radiographic assessment proceeded to radical colorectal cancer surgery. Following surgery, patients in both groups were to complete an additional four cycles of CAPOX chemotherapy. We compared and analyzed the short- and long-term clinical outcomes between the Tislelizumab plus CAPOX regimen and CAPOX alone for the treatment of microsatellite stable (MSS)-type high-risk locally advanced colon cancer (stages T4NanyM0 or TanyN+M0).

Enrollment: 94 estimated patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

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 ≥ 60g/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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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94 participants in 2 patient groups, including a placebo group

CAPOX combined with Tislelizumab

Experimental group

Description:

Patients in the experimental group underwent two or four cycles of preoperative CAPOX combined with Tislelizumab. Patients assessed as suitable for R0 resection by imaging underwent radical colectomy. Following surgery, all patients in both groups completed an additional four or six cycles of adjuvant CAPOX chemotherapy.

Treatment:

Drug: Oxaliplatin

Drug: Tislelizumab

Drug: Capecitabine

CAPOX chemotherapy

Placebo Comparator group

Description:

Patients in the experimental group underwent two or four cycles of preoperative CAPOX combined with placebo. Patients assessed as suitable for R0 resection by imaging underwent radical colectomy. Following surgery, all patients in both groups completed an additional four or six cycles of adjuvant CAPOX chemotherapy.

Treatment:

Drug: Oxaliplatin

Drug: Capecitabine