Combination of Toripalimab and Celecoxib for Advanced Colorectal Cancer

Neoadjuvant Toripalimab Plus Celecoxib in Mismatch-repair Deficient or Microsatellite Instability-high Locally Advanced Colorectal Cancer (PICC-3): a Multicenter, Single-arm, Phase 2 Trial

This study is testing if a combination of two medications, Toripalimab and Celecoxib, can help patients with advanced colorectal cancer avoid surgery and improve their treatment outcomes.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 105 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Sun Yat-sen University (Academic / other)
• Drugs / interventions: chemotherapy, radiation, immunotherapy
• Locations: 1 site (Guangzhou, Guangdong)
• Trial ID: NCT06903858 on ClinicalTrials.gov

What this trial studies

This clinical trial investigates the use of Toripalimab, an immune checkpoint inhibitor, combined with Celecoxib for patients with locally advanced colorectal cancer that is deficient in mismatch repair (dMMR) or has high microsatellite instability (MSI-H). The approach aims to evaluate the effectiveness and tolerability of this neoadjuvant treatment, potentially allowing patients to avoid surgical resection. The study focuses on patients who have not received prior anti-cancer therapies and have a confirmed diagnosis of colorectal adenocarcinoma. The trial will assess clinical and pathological responses to determine if non-surgical treatment can be a viable option for these patients.

Who should consider this trial

Good fit: Ideal candidates include adults aged 18 and older with locally advanced dMMR or MSI-H colorectal adenocarcinoma who have not undergone prior cancer treatments.

Not a fit: Patients with distant metastases or those requiring emergency surgery due to complications like intestinal obstruction or active bleeding may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a non-surgical option for patients with advanced colorectal cancer, reducing the risks associated with surgery.

How similar studies have performed: Previous Phase II studies have shown promising results for neoadjuvant immune checkpoint inhibitor treatments in similar patient populations, indicating a potential for success.

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.

Where this trial is running

Guangzhou, Guangdong

• The Sixth Affiliated Hospital, Sun Yat-sen University — Guangzhou, Guangdong, China (Recruiting)

Study contacts

• Study coordinator: Yanhong Deng, MD.

Conditions Colorectal Cancer; PD-1 Inhibitor; Neoadjuvant Immunotherapy; Celecoxib; Watch &Amp; Wait