NCT06002789

Safety and Efficacy of PD-1 ± mFOLFOX6 Neoadjuvant Therapy in Local Advanced sMPCC

Safety and Efficacy of PD-1 Monoclonal Antibody With or Without mFOLFOX6 Neoadjuvant Therapy in Patients With Local Advanced Deficient Mismatch Repair/Microsatellite Instability-high Synchronous Multiple Primary Colorectal Cancer (sMPCC)

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 17 (estimated)
• Sponsor: Sixth Affiliated Hospital, Sun Yat-sen University · Academic / Other
• Sex: All
• Age: 18 Years – 80 Years
• Healthy volunteers: Not accepted

Summary

At present, radical resection ± preoperative neoadjuvant chemotherapy for colorectal cancer is still the standard comprehensive treatment. In recent years, immunotherapy of PD-1 monoclonal antibody has a significant effect in the second-line/first-line treatment of dMMR/MSI-H advanced colorectal cancer and the neoadjuvant treatment of early colorectal cancer. Synchronous multiple primary colorectal cancer (sMPCC) is a relatively rare type of colorectal cancer (CRC) that refers to the simultaneous occurrence of 2 or more independent primary malignancies in the colon or rectum. The recent large-scale, single-center retrospective study of the investigator showed that compared with single primary colorectal cancer (SPCRC)patients, the incidence of dMMR/MSI-H was significantly higher in sMPCC patients. Besides, a certain proportion of sMPCC patients could both have MSI and MSS tumors at the same time. There is no standard regimen for this patients so far. This study intends to treat the MSI-H/MSS (dMMR/pMMR) mixed sMPCC patients with combination of mFOLFOX6+PD-1 monoclonal antibody neoadjuvant therapy, and treat the all-MSI-H (dMMR) sMPCC patients with single-drug PD-1 monoclonal antibody neoadjuvant therapy. Given the current gaps in the guideline, the investigator intends to take the lead in carrying out this open, multi-center, prospective clinical phase II study. This study might provide a clinical evidence for individual treatment of sMPCC patients, in preserving the functions and organs to the greatest extent.

Detailed description

Colorectal cancer is one of the most common malignant tumors in the world. At present, radical resection ± preoperative neoadjuvant chemotherapy for colorectal cancer is still the standard comprehensive treatment recommended by the two major international guidelines of NCCN and ESMO, as well as the Chinese CSCO guidelines. Mismatch repair protein (MMR) expression and microsatellite instability (MSI) status are important factors affecting the efficacy of immunotherapy. In recent years, immunotherapy of PD-1 monoclonal antibody has a significant effect in the second-line/first-line treatment of dMMR/MSI-H advanced colorectal cancer and the neoadjuvant treatment of early colorectal cancer, all of which have shown very good efficacy with great safety and tolerable toxicity. Synchronous multiple primary colorectal cancer (sMPCC) is a relatively rare type of colorectal cancer (CRC) that refers to the simultaneous occurrence of 2 or more independent primary malignancies in the colon or rectum of the same patient. Since 2000, the annual incidence and mortality of CRC in China have continued to increase, and the incidence of sMPCC has also increased. The overall incidence of sMPCC ranges from 1.1% to 8.1% of CRC patients. The recent large-scale, single-center retrospective study of the investigator showed that among 239 sMPCC patients, the proportions of all-pMMR, all-dMMR, and mixed types (pMMR/dMMR) were 189 (79.1%), 40 (16.7%), and 10 (4.2%), respectively. Compared with single primary colorectal cancer (SPCRC) patients, the incidence of dMMR was significantly higher in sMPCC patients (50/239 vs 872/13037). The results of NGS detection of MSI status were consistent with the results of Immunohistochemistry (IHC), 21.8% (17/78) of sMPCC patients were MSI-H, while the proportion was only 5.3% (5/94) in SPCRC patients. At present, single-drug PD-1 or combined with other immunotherapy has become the first-line treatment for MSI-H SPCRC patients. However, there is no standard regimen for some sMPCC patients who both have MSI-H and MSS lesions. Moreover, there are no studies and reports on the treatment of mFOLFOX6+PD-1 monoclonal antibody in MSI-H/MSS mixed sMPCC and PD-1 monoclonal antibody in all-MSI-H sMPCC. This study intends to treat the MSI-H/MSS (dMMR/pMMR) mixed sMPCC patients with combination of mFOLFOX6+PD-1 monoclonal antibody neoadjuvant therapy, and treat the all-MSI-H (dMMR) sMPCC patients with single-drug PD-1 monoclonal antibody neoadjuvant therapy. As one of the largest single centers for the diagnosis and treatment of colorectal cancer in China, the Sixth Affiliated Hospital of Sun Yat-sen University has performed nearly 4,000 cases of colorectal cancer surgery per year. Therefore, the investigator intends to take the lead in carrying out this open, multi-center, prospective clinical phase II study in the world. The investigator will give different treatments by the result of microsatellite instability status of all lesions in sMPCC. The pCR rate, incidence of AEs of neoadjuvant therapy, R0 resection rate, down-stage rate, 3 years DFS rate and OS rate are analyzed. This study might provide a clinical evidence for individual treatment of sMPCC patients, in preserving the functions and organs to the greatest extent.

Conditions

• Multiple Cancer
• Colorectal Cancer

Interventions

Type	Name	Description
DRUG	MSI-H/MSS (dMMR/pMMR) mixed sMPCC: combination of mFOLFOX6+PD-1 monoclonal antibody neoadjuvant therapy	For MSI-H/MSS (dMMR/pMMR) mixed sMPCC, a combination of neoadjuvant chemotherapy with mFOLFOX6 and immunotherapy with PD-1 monoclonal antibody are applied.
DRUG	All-MSI-H (dMMR) sMPCC: single-drug PD-1 monoclonal antibody neoadjuvant therapy	For all-MSI-H (dMMR) sMPCC, single-drug PD-1 monoclonal antibody immunotherapy is applied.

Timeline

• Start date: 2022-05-01
• Primary completion: 2027-09-01
• Completion: 2028-12-01
• First posted: 2023-08-21
• Last updated: 2025-01-22

Locations

1 site across 1 country: China