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Recruiting Phase 2

Neoadjuvant Toripalimab With or Without Celecoxib in dMMR/MSI-H Colorectal Cancer

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About this study

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.

Condition
Colorectal Cancer, Mismatch Repair-deficient (dMMR), Microsatellite Instability-high (MSI-H), Neoadjuvant Therapy
Tested
Neoadjuvant toripalimab plus celecoxib for 6 cycles, Neoadjuvant toripalimab monotherapy for 6 cycles, Neoadjuvant torip...
Sponsor
Sun Yat-sen University

Who can join

Age
18 to 75 years
Sex
All sexes
Healthy volunteers
Not accepted

Inclusion 12

  • Minimum age: 18 years
  • Maximum age: 75 years
  • Study condition: Colorectal Cancer, Mismatch Repair-deficient (dMMR), Microsatellite Instability-high (MSI-H), Neoadjuvant Therapy
  • 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 aged 18 to 75 years.
  • 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.
  • Adequate bone marrow, hepatic and renal function as assessed by the following laboratory requirements conducted within 7 days of starting study treatment.

Exclusion 10

  • Previous or concurrent cancer that is distinct in primary site or histology from colorectal 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.

Where

1 site, 1 recruiting

The Sixth Affiliated Hospital of Sun Yat-sen University

Guangzhou, Guangdong, China

Recruiting

Contact

Potential match only. Final eligibility is determined by the study team.