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

Launched by SUN YAT-SEN UNIVERSITY · Mar 28, 2025

Keywords

ClinConnect Summary

This clinical trial is studying a new treatment approach for patients with locally advanced colorectal cancer that has specific genetic features, known as dMMR or MSI-H. The treatment combines two medications: Toripalimab, which helps the immune system fight cancer, and Celecoxib, a common anti-inflammatory drug. The goal is to see if this combination can effectively shrink tumors and potentially allow patients to avoid surgery altogether, which can have serious risks and side effects.

To participate in this trial, you must be at least 18 years old and have been diagnosed with a specific type of colorectal cancer that has not been treated before. You should also be in overall good health, with no other serious medical conditions that could complicate your treatment. If you join the trial, you can expect to receive the study medications and be monitored closely by the research team for any side effects or changes in your condition. This trial is an exciting opportunity to explore less invasive treatment options, which could improve outcomes and quality of life for patients with this type of cancer.

Gender

ALL

Eligibility criteria

• Inclusion Criteria:
• • 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.
• Exclusion Criteria:
• • 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.