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

Not Applicable
Not yet recruiting
Conditions
Colonic Neoplasms
Neoadjuvant Therapy
Immune Checkpoint Inhibitors
Interventions
Registration Number
NCT07132008
Lead Sponsor
First Affiliated Hospital of Guangxi Medical University
Brief Summary

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.

Detailed 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).

Recruitment & Eligibility

Status
NOT_YET_RECRUITING
Sex
All
Target Recruitment
94
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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
CAPOX combined with TislelizumabTislelizumabPatients 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.
CAPOX combined with TislelizumabOxaliplatinPatients 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.
CAPOX combined with TislelizumabCapecitabinePatients 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.
CAPOX chemotherapyOxaliplatinPatients 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.
CAPOX chemotherapyCapecitabinePatients 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.
Primary Outcome Measures
NameTimeMethod
Pathological complete response (pCR)3-5 days 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
NameTimeMethod
R0 resection3-5 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.

Overall survival (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.

3-year overall survival

Disease-free survival (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.

3-year disease-free survival

Adverse events (AEs)up to half a year

the rate of adverse events

Surgical complicationFrom the day of surgery to 30 days after the operation, including intraoperative and postoperative complications.

the rate of surgical complication during or after operation.

Immune-related adverse events (irAEs)up to half a year

the rate of immune-related adverse events

Trial Locations

Locations (1)

The First Affiliated Hospital of Guangxi Medical University

🇨🇳

Nanning, Guangxi, China

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

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