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

NCT06903858 | Recruiting Phase 2

• 1 other identifier: CSWOG-C08
• Study Type: interventional
• Target: 105
• Locations: 1 country
• Sites: 1

Brief Summary

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

Colorectal Cancer (CRC); PD-1 Inhibitor; Neoadjuvant Immunotherapy; Celecoxib; Watch &Amp; Wait

Outcome Measures

Primary Outcomes (1)

• Event-free survival (EFS)

  the time between randomization and one of the following events: locally progressive disease leading to an unresectable tumor, local R2 resection, local recurrence after an R0/1 resection, distant metastases, a new primary colorectal cancer, or death from any cause, whichever occurred first.

  3 years

Secondary Outcomes (2)

• Pathologic complete response (pCR) rate

  3 years

• Overall survival (OS)

  3 years

Study Arms (1)

Neoadjuvant Toripalimab plus Celecoxib

EXPERIMENTAL

Neoadjuvant Treatment Phase Toripalimab is administered via intravenous infusion at 3 mg/kg over 30 minutes (initial infusion time is 60 minutes), once every two weeks, for a total of 12 doses before surgery. Celecoxib is taken orally at 200 mg per dose, twice daily, for a duration of 6 months. Assessment After Neoadjuvant Treatment 1. Patients achieving clinical complete response (cCR) based on radiographic imaging (CT/MRI of chest, abdomen, pelvis, and rectal MRI), endoscopy, and digital rectal examination (if applicable) are recommended to adopt a watch-and-wait strategy. 2. Patients who do not achieve cCR based on radiographic imaging (CT/MRI of chest, abdomen, pelvis, and rectal MRI), endoscopy, and digital rectal examination (if applicable) are recommended to undergo curative resection of colorectal cancer.

Drug: Toripalimab combined with celecoxib; Procedure: Curative resection of colorectal cancer; Other: Watch-and-wait strategy

Interventions

Toripalimab combined with celecoxib DRUG

Toripalimab is administered via intravenous infusion at 3 mg/kg over 30 minutes (initial infusion time is 60 minutes), once every two weeks, for a total of 12 doses before surgery. Celecoxib is taken orally at 200 mg per dose, twice daily, for a duration of 6 months.

Neoadjuvant Toripalimab plus Celecoxib

Curative resection of colorectal cancer PROCEDURE

Patients who do not achieve cCR based on radiographic imaging (CT/MRI of chest, abdomen, pelvis, and rectal MRI), endoscopy, and digital rectal examination (if applicable) are recommended to undergo curative resection of colorectal cancer.

Neoadjuvant Toripalimab plus Celecoxib

Watch-and-wait strategy OTHER

Patients achieving clinical complete response (cCR) based on radiographic imaging (CT/MRI of chest, abdomen, pelvis, and rectal MRI), endoscopy, and digital rectal examination (if applicable) are recommended to adopt a watch-and-wait strategy.

Neoadjuvant Toripalimab plus Celecoxib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed informed consent and willingness/compliance with study procedures.
• Age ≥18 years.
• Histologically confirmed colorectal adenocarcinoma.
• ECOG performance status 0-1.
• Locally advanced primary tumor (T3/T4 and/or N+) confirmed by CT/MRI (pelvic MRI for rectal cancer).
• dMMR (IHC) or MSI-H (PCR) status.
• No prior anti-cancer therapy for colonrectal cancer (surgery/chemotherapy/targeted therapy/radiation).
• Adequate organ function
• 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.
• Willingness to adhere to study requirements.

You may not qualify if:

• Presence of distant metastases (M1) confirmed by CT/MRI or PET-CT (at least covering the chest, abdomen, and pelvis).
• Complete intestinal obstruction, active bleeding, or perforation requiring emergency surgery.
• Inability to achieve complete resection of the primary colorectal tumor.
• History or concurrent active malignancy (except malignancies cured ≥5 years ago or adequately treated carcinoma in situ).
• 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.
• Major surgery (e.g., laparotomy, thoracotomy, organ resection via laparoscopy) or severe trauma within 4 weeks before enrollment (surgical incision must be fully healed).
• Thromboembolic events (e.g., cerebrovascular accident, transient ischemic attack, pulmonary embolism, deep vein thrombosis) within 12 months before enrollment.
• Active coronary artery disease, severe/unstable angina, or newly diagnosed angina/myocardial infarction within 12 months before enrollment.
• New York Heart Association (NYHA) Class II or higher congestive heart failure (see Appendix 3).
• HIV infection, AIDS, or untreated active hepatitis (HBV-DNA ≥500 IU/mL; HCV-RNA above detection limit).
• Active inflammatory bowel disease or other colorectal disorders causing chronic diarrhea.
• 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).
• Interstitial lung disease, non-infectious pneumonitis, or uncontrolled systemic diseases (e.g., diabetes, hypertension, pulmonary fibrosis, acute pneumonia).
• Residual toxicity ≥Grade 2 (per CTCAE v5.0) from prior therapies (except anemia, alopecia, skin pigmentation).
• Known or suspected hypersensitivity to any study-related drugs.

Sponsors & Collaborators

• Sun Yat-sen University: lead

Study Sites (1)

The Sixth Affiliated Hospital, Sun Yat-sen University

Guangzhou, Guangdong, 510655, China

RECRUITING

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Celecoxib

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Benzenesulfonamides; Sulfonamides; Amides; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Sulfones; Sulfur Compounds; Pyrazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Central Study Contacts

Yanhong Deng, MD.

CONTACT

020-38379762; dengyanh@mail.sysu.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Masking Details: Open Label
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: Prospective, Multicenter, Single-arm, Phase II

Study Record Dates

• First Submitted: March 28, 2025
• First Posted: April 1, 2025
• Study Start: April 1, 2025
• Primary Completion (Estimated): April 1, 2028
• Study Completion (Estimated): April 1, 2031
• Last Updated: April 1, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)