Actively Recruiting

Phase 2
Age: 18Years - 75Years
All Genders
NCT03926338

Neoadjuvant Toripalimab With or Without Celecoxib in dMMR/MSI-H Colorectal Cancer

Led by Sun Yat-sen University · Updated on 2025-11-20

270

Participants Needed

1

Research Sites

568 weeks

Total Duration

On this page

AI-Summary

What this Trial Is About

Colorectal cancer of Mismatch Repair-deficient (dMMR)/ Microsatellite Instability-high (MSI-H) accounts for approximately 15% of all colorectal cancer patients, with a higher proportion in right colon cancer. Previous studies have found that colon cancer patients with dMMR/MSI-H cannot benefit from 5-fluorouracil (5-FU) adjuvant chemotherapy. Once patients have distant metastases, they are not sensitive to traditional palliative chemotherapy, and the prognosis is significantly worse than that of mismatch repair-proficient (pMMR)/microsatellite stability (MSS). A phase II clinical study of anti-PD-1 immunotherapy based on mismatch repair (MMR) status published in 《N Engl J Med》 showed that the objective response rate (ORR) of advanced colorectal cancer patients with dMMR received anti-PD-1 is 40%, and a longer response time can be obtained compared to conventional chemotherapy. Anti-PD-1 neoadjuvant therapy has proven to be safe and feasible in lung cancer, bladder cancer and malignant melanoma, and can achieve more than 40% of major pathological response. However, there are no reports of anti-PD-1 neoadjuvant therapy for the dMMR/MSI-H colorectal cancer. Therefore, the aim of this study was to find the best multidisciplinary treatment for resectable colorectal cancer patient with the dMMR/MSI-H phenotype and to explore whether cyclooxygenase (COX) inhibitors combined with anti-PD-1 monoclonal antibody (mAb) could further improve efficacy.

CONDITIONS

Official Title

Neoadjuvant Toripalimab With or Without Celecoxib in dMMR/MSI-H Colorectal Cancer

Who Can Participate

Age: 18Years - 75Years
All Genders

Eligibility Criteria

Eligible

You may qualify if you...

  • Willing and able to provide written informed consent.
  • Histological or cytological documentation of adenocarcinoma of the colon or rectum.
  • Tumor tissues identified as mismatch repair-deficient (dMMR) by immunohistochemistry or microsatellite instability-high (MSI-H) by PCR.
  • Male or female subjects aged 18 to 75 years.
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
  • CT or MRI scans within 14 days showing locally advanced (cT3-4 or cN1-2) cancer.
  • Non complicated primary tumor (no obstruction, perforation, or bleeding).
  • No previous systemic anticancer therapy for colorectal cancer.
  • Adequate bone marrow, liver, and kidney function based on lab tests within 7 days before treatment.
Not Eligible

You will not qualify if you...

  • Previous or concurrent cancer distinct from colorectal cancer within 5 years before randomization.
  • Significant cardiovascular disease including unstable angina or heart attack within 6 months before treatment.
  • Heart failure grade III or IV.
  • Unresolved toxicity higher than Grade 1 from any prior therapy.
  • Known allergy to study drugs or their components.
  • Current or recent (within 4 weeks) participation in another investigational drug study.
  • Pregnant or breastfeeding women.
  • Lack of effective contraception.
  • Previous treatment with anti-PD-1, anti-PD-L1, anti-CTLA-4 antibodies, or other T cell checkpoint therapies.
  • Presence of any distant metastasis.

AI-Screening

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Trial Site Locations

Total: 1 location

1

The Sixth Affiliated Hospital of Sun Yat-sen University

Guangzhou, Guangdong, China, 510655

Actively Recruiting

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Research Team

Y

Yanhong Deng, M.D.

CONTACT

How is the study designed?

Study Type

INTERVENTIONAL

Masking

SINGLE

Allocation

RANDOMIZED

Model

SEQUENTIAL

Primary Purpose

TREATMENT

Number of Arms

3

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