Neoadjuvant therapy for colorectal cancer using toripalimab with or without celecoxib

Neoadjuvant PD-1 Blockade by Toripalimab With or Without Celecoxib in Mismatch-repair Deficient or Microsatellite Instability-high Locally Advanced Colorectal Cancer (PICC)

This study is testing if adding celecoxib to the immunotherapy toripalimab can help people with certain types of colorectal cancer feel better before surgery.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 270 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Sun Yat-sen University (Academic / other)
• Drugs / interventions: chemotherapy, immunotherapy, toripalimab
• Locations: 1 site (Guangzhou, Guangdong)
• Trial ID: NCT03926338 on ClinicalTrials.gov

What this trial studies

This clinical trial investigates the effectiveness of toripalimab, an anti-PD-1 immunotherapy, combined with celecoxib, in treating patients with resectable colorectal cancer characterized by mismatch repair deficiency (dMMR) or high microsatellite instability (MSI-H). Participants will receive either a combination of toripalimab and celecoxib or toripalimab alone for a duration of 3 to 6 months before surgical resection. The study aims to evaluate the safety and efficacy of these treatment regimens in improving patient outcomes compared to traditional therapies. The trial is particularly focused on patients who have not previously undergone systemic anticancer therapy for their colorectal cancer.

Who should consider this trial

Good fit: Ideal candidates for this study are adults aged 18 and older with histologically confirmed dMMR/MSI-H colorectal adenocarcinoma who have not received prior systemic anticancer therapy.

Not a fit: Patients with mismatch repair-proficient (pMMR) colorectal cancer or those who have previously received systemic anticancer therapy may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a more effective neoadjuvant therapy option for patients with dMMR/MSI-H colorectal cancer, potentially improving surgical outcomes and overall survival.

How similar studies have performed: Previous studies have shown promising results with anti-PD-1 therapies in similar patient populations, indicating potential for success in this approach.

Eligibility criteria

Inclusion Criteria:

1. Willing and able to provide written informed consent.
2. Histological or cytological documentation of adenocarcinoma of the colon or rectum.
3. Tumor tissues were identified as mismatch repair-deficient (dMMR) by immunohistochemistry (IHC) method or microsatellite instability-high (MSI-H) by polymerase chain reaction (PCR).
4. Male or female subjects aged 18 to 75 years.
5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
6. Determined CT or MRI scans (done within 14 days of registration) of the chest, abdomen and pelvis: locally advanced (cT3-4 or cN1-2 \[with the definition of a clinically positive lymph node being any node ≥ 1.0 cm\]).
7. Non complicated primary tumor (obstruction, perforation, bleeding).
8. No previous any systemic anticancer therapy for colorectal cancer disease.
9. Adequate bone marrow, hepatic and renal function as assessed by the following laboratory requirements conducted within 7 days of starting study treatment.

Exclusion Criteria:

1. Previous or concurrent cancer that is distinct in primary site or histology from colorectal cancer within 5 years prior to randomization.
2. Significant cardiovascular disease including unstable angina or myocardial infarction within 6 months before initiating study treatment.
3. Heart failure grade III/IV (NYHA-classification).
4. Unresolved toxicity higher than CTCAE v.4.0 Grade 1 attributed to any prior therapy/procedure.
5. Subjects with known allergy to the study drugs or to any of its excipients.
6. Current or recent (within 4 weeks prior to starting study treatment) treatment of another investigational drug or participation in another investigational study.
7. Breast- feeding or pregnant women
8. Lack of effective contraception.
9. Previously received anti-programmed death-1 (PD-1) or its ligand (PD-L1) antibody, anti-cytotoxic T lymphocyte-associated antigen 4 (cytotoxic T-lymphocyte-associated Protein 4, CTLA-4) antibody or other drug/antibody that acts on T cell costimulation or checkpoint pathways.
10. With any distant metastasis.

Where this trial is running

Guangzhou, Guangdong

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

Study contacts

• Principal investigator: Yanhong Deng, M.D. — Sixth Affiliated Hospital, Sun Yat-sen University
• Study coordinator: Yanhong Deng, M.D.

Conditions Colorectal Cancer; Mismatch Repair-deficient; Microsatellite Instability-high; Neoadjuvant Therapy