Toripalimab With or Without Celecoxib as Neoadjuvant Therapy in Resectable dMMR/MSI-H Colorectal Cancer (PICC)

  • STATUS
    Recruiting
  • End date
    May 1, 2024
  • participants needed
    100
  • sponsor
    Sun Yat-sen University
Updated on 7 October 2022
monoclonal antibodies
fluorouracil
celecoxib
lung cancer
metastasis
oxaliplatin
capecitabine
irinotecan
colon cancer
adjuvant therapy
adenocarcinoma
adjuvant chemotherapy
adenocarcinoma of colon

Summary

Colorectal cancer of Mismatch Repair-deficient (dMMR)/ Microsatellite Instability-high (MSI-H) accounts for approximately 15% of all colorectal cancer patients, with a higher proportion in right colon cancer. Previous studies have found that colon cancer patients with dMMR/MSI-H cannot benefit from 5-fluorouracil (5-FU) adjuvant chemotherapy. Once patients have distant metastases, they are not sensitive to traditional palliative chemotherapy, and the prognosis is significantly worse than that of mismatch repair-proficient (pMMR)/microsatellite stability (MSS). A phase II clinical study of anti-PD-1 immunotherapy based on mismatch repair (MMR) status published in 《N Engl J Med》 showed that the objective response rate (ORR) of advanced colorectal cancer patients with dMMR received anti-PD-1 is 40%, and a longer response time can be obtained compared to conventional chemotherapy.

Anti-PD-1 neoadjuvant therapy has proven to be safe and feasible in lung cancer, bladder cancer and malignant melanoma, and can achieve more than 40% of major pathological response. However, there are no reports of anti-PD-1 neoadjuvant therapy for the dMMR/MSI-H colorectal cancer. Therefore, the aim of this study was to find the best multidisciplinary treatment for resectable colorectal cancer patient with the dMMR/MSI-H phenotype and to explore whether cyclooxygenase (COX) inhibitors combined with anti-PD-1 monoclonal antibody (mAb) could further improve efficacy.

Details
Condition Colorectal Cancer, Mismatch Repair-deficient (dMMR), Microsatellite Instability-high (MSI-H), Neoadjuvant Therapy
Treatment Neoadjuvant therapy with PD-1 inhibitor plus COX inhibitor, Neoadjuvant therapy with PD-1 inhibitor
Clinical Study IdentifierNCT03926338
SponsorSun Yat-sen University
Last Modified on7 October 2022

Eligibility

Yes No Not Sure

Inclusion Criteria

Willing and able to provide written informed consent
Histological or cytological documentation of adenocarcinoma of the colon or rectum
Tumor tissues were identified as mismatch repair-deficient (dMMR) by immunohistochemistry (IHC) method or microsatellite instability-high (MSI-H) by polymerase chain reaction (PCR)
Male or female subjects ≧ 18 years ≦ 75 of age
Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
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])
Non complicated primary tumor (obstruction, perforation, bleeding)
No previous any systemic anticancer therapy for colorectal cancer disease or radiologic evaluation of tumor regression < 20% or unacceptable toxic effects during neoadjuvant chemotherapy
Adequate bone marrow, hepatic and renal function as assessed by the following laboratory requirements conducted within 7 days of starting study treatment

Exclusion Criteria

Previous or concurrent cancer that is distinct in primary site or histology from colon cancer within 5 years prior to randomization
Significant cardiovascular disease including unstable angina or myocardial infarction within 6 months before initiating study treatment
Heart failure grade III/IV (NYHA-classification)
Unresolved toxicity higher than CTCAE v.4.0 Grade 1 attributed to any prior therapy/procedure
Subjects with known allergy to the study drugs or to any of its excipients
Current or recent (within 4 weeks prior to starting study treatment) treatment of another investigational drug or participation in another investigational study
Breast- feeding or pregnant women
Lack of effective contraception
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
With any distant metastasis
Clear my responses

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