Actively Recruiting

Phase 2
Age: 18Years +
All Genders
NCT06903858

Neoadjuvant Toripalimab Plus Celecoxib for dMMR/MSI-H Locally Advanced Colorectal Cancer

Led by Sun Yat-sen University · Updated on 2025-04-01

105

Participants Needed

1

Research Sites

313 weeks

Total Duration

On this page

AI-Summary

What this Trial Is About

Several Phase II studies have demonstrated the feasibility, effectiveness, and good tolerability of neoadjuvant immune checkpoint inhibitor (ICI) treatment for localized dMMR colorectal and rectal cancers. The significant clinical and pathological complete response rates offer the possibility of avoiding surgical resection. dMMR colorectal cancers are generally larger and more advanced than pMMR tumors, often requiring more extensive surgery with associated risks such as anastomotic leakage, ureteral injury, and infection. If oncological outcomes are not affected (requiring long-term follow-up), non-surgical treatment becomes an attractive option for localized dMMR colorectal cancer. Moreover, pelvic radiotherapy, the standard for locally advanced rectal cancer, causes both short-term and long-term adverse effects (e.g., bowel and bladder dysfunction, fistula, infertility), significantly impacting quality of life. Total mesorectal excision also carries risks of complications and sexual dysfunction, often requiring a stoma, making organ preservation a more urgent need for rectal cancer patients. Phase II trials and the international "watch-and-wait" database have confirmed the feasibility and safety of organ preservation for pMMR locally advanced rectal cancer. Therefore, the high clinical and pathological complete response rates achieved by neoadjuvant immunotherapy for dMMR/MSI-H rectal cancer offer promising prospects for non-surgical treatment.

CONDITIONS

Official Title

Neoadjuvant Toripalimab Plus Celecoxib for dMMR/MSI-H Locally Advanced Colorectal Cancer

Who Can Participate

Age: 18Years +
All Genders

Eligibility Criteria

Eligible

You may qualify if you...

  1. Signed informed consent and willingness/compliance with study procedures.
  2. Age ≥18 years.
  3. Histologically confirmed colorectal adenocarcinoma.
  4. ECOG performance status 0-1.
  5. Locally advanced primary tumor (T3/T4 and/or N+) confirmed by CT/MRI (pelvic MRI for rectal cancer).
  6. dMMR (IHC) or MSI-H (PCR) status.
  7. No prior anti-cancer therapy for colonrectal cancer (surgery/chemotherapy/targeted therapy/radiation).
  8. Adequate organ function
  9. For women of childbearing potential: negative pregnancy test and contraception use during and for 3 months post-treatment. Male participants with fertile partners must use contraception.
  10. Willingness to adhere to study requirements.
Not Eligible

You will not qualify if you...

  1. Presence of distant metastases (M1) confirmed by CT/MRI or PET-CT (at least covering the chest, abdomen, and pelvis).
  2. Complete intestinal obstruction, active bleeding, or perforation requiring emergency surgery.
  3. Inability to achieve complete resection of the primary colorectal tumor.
  4. History or concurrent active malignancy (except malignancies cured ≥5 years ago or adequately treated carcinoma in situ).
  5. Prior treatment with anti-PD-1/PD-L1 antibodies, anti-CTLA-4 antibodies, or other drugs/antibodies targeting T-cell co-stimulation or checkpoint pathways.
  6. Major surgery (e.g., laparotomy, thoracotomy, organ resection via laparoscopy) or severe trauma within 4 weeks before enrollment (surgical incision must be fully healed).
  7. Thromboembolic events (e.g., cerebrovascular accident, transient ischemic attack, pulmonary embolism, deep vein thrombosis) within 12 months before enrollment.
  8. Active coronary artery disease, severe/unstable angina, or newly diagnosed angina/myocardial infarction within 12 months before enrollment.
  9. New York Heart Association (NYHA) Class II or higher congestive heart failure (see Appendix 3).
  10. HIV infection, AIDS, or untreated active hepatitis (HBV-DNA ≥500 IU/mL; HCV-RNA above detection limit).
  11. Active inflammatory bowel disease or other colorectal disorders causing chronic diarrhea.
  12. Active, known, or suspected autoimmune disease (exceptions: stable conditions like type 1 diabetes, hypothyroidism on hormone replacement, or skin disorders without systemic treatment, e.g., vitiligo, psoriasis, alopecia).
  13. Interstitial lung disease, non-infectious pneumonitis, or uncontrolled systemic diseases (e.g., diabetes, hypertension, pulmonary fibrosis, acute pneumonia).
  14. Residual toxicity ≥Grade 2 (per CTCAE v5.0) from prior therapies (except anemia, alopecia, skin pigmentation).
  15. Known or suspected hypersensitivity to any study-related drugs.
  16. Pregnancy or lactation.
  17. Women of childbearing potential (last menstruation <2 years ago) or fertile men unwilling to use effective non-hormonal contraception.
  18. Any unstable medical condition compromising safety or protocol compliance.

AI-Screening

AI-Powered Screening

Complete this quick 3-step screening to check your eligibility

1
2
3
+1

Trial Site Locations

Total: 1 location

1

The Sixth Affiliated Hospital, Sun Yat-sen University

Guangzhou, Guangdong, China, 510655

Actively Recruiting

Loading map...

Research Team

Y

Yanhong Deng, MD.

CONTACT

How is the study designed?

Study Type

INTERVENTIONAL

Masking

NONE

Allocation

NON_RANDOMIZED

Model

SINGLE_GROUP

Primary Purpose

TREATMENT

Number of Arms

1

Not the Right Trial for You?

Explore thousands of other clinical trials that might be a better match.
Sign up to get personalized trial recommendations delivered to your inbox.

Already have an account? Log in here