NCT06931808

Intestinal Microbiota Transplantation, Radiochemotherapy and Sintilimab in Localized Advanced Colon Cancer

The Efficacy and Safety of Intestinal Microbiota Transplantation Combined With Radiochemotherapy and Sintilimab in Neoadjuvant Treatment for Locally Advanced Rectal cancer-a Single Arm, Prospective, Single Center Exploratory Study

• Status: Enrolling By Invitation
• Phase: Phase 4
• Study type: Interventional
• Enrollment: 20 (estimated)
• Sponsor: First Affiliated Hospital of Ningbo University · Network
• Sex: All
• Age: 18 Years – 75 Years
• Healthy volunteers: Not accepted

Summary

The standard treatment for locally advanced rectal cancer is neoadjuvant chemoradiotherapy followed by total mesorectal excision. While Immune checkpoint inhibitors are promising in the treatment of various cancers, the combination of radiotherapy and immunotherapy still lacks high-level evidence-based medicine, and the efficacy is still limited in rectal cancer. Thus, we designed a study on the efficacy and safety of intestinal microbiota transplantation combined with synchronous radiochemotherapy and immune checkpoint inhibitor xindilimab neoadjuvant therapy for locally advanced rectal cancer.

Detailed description

The incidence rate of colorectal cancer (CRC) ranks among the top three most common cancers in the world, while the mortality rate ranks among the top two. Early symptoms of rectal cancer are not obvious, and about 60% of patients are diagnosed with locally advanced rectal cancer. The standard treatment for locally advanced rectal cancer is neoadjuvant chemoradiotherapy followed by total mesorectal excision. However, the response of patients to radiotherapy showed significant heterogeneity, with pathological complete response rates (pCR) ranging from 6% to 39%. In addition, a significant proportion of LARC patients (20% -40%) do not respond to preoperative radiotherapy (preRT). Therefore, it is crucial to find ways to alleviate radiation resistance within tumors. Immune checkpoint inhibitors (ICIs) are increasingly being used in various solid tumors. However, immunotherapy in the field of CRC has always been distinct, with patients with mismatch repair defects (dMMR) or high microsatellite instability (MSI-H) (accounting for 5% -15% of all CRCs) having a higher tumor mutation burden (TMB) and more tumor infiltrating lymphocytes (TILs), making them the absolute dominant population for immunotherapy; However, patients with microsatellite stability (MSS) or normal mismatch repair (pMMR) have poor immune therapy efficacy. At present, radiotherapy is widely regarded as a mechanism that triggers local and systemic immune responses, providing a theoretical basis for the combination of radiotherapy and immunotherapy (iRT). In 2022, the VOLTAGE-A study reported the addition of nivolumab treatment after long-term synchronous chemoradiotherapy. The results showed that the major pathological response (MPR) rate and pCR rate in 37 MSS LARC patients after surgery were 38% and 30%, respectively. In addition, multiple studies have conducted similar explorations with different methods. Overall, these studies have achieved certain therapeutic effects, with pCR rates ranging from 37.5% to 57.1%. However, the combination of radiotherapy and immunotherapy still lacks high-level evidence-based medicine, and the efficacy is still limited. The gut microbiota is a complex microbial community closely related to the occurrence and development of rectal cancer. Previous studies have shown that gut microbiota can predict response to neoadjuvant radiotherapy, improve treatment response, and reduce treatment toxicity. In addition, it has been confirmed that the gut microbiota can reshape the tumor immune microenvironment (TiME), thereby affecting the response to ICIs. The results of two Phase I trials indicate that gut microbiota transplantation (FMT) derived from responders effectively reversed immune resistance in melanoma, laying the foundation for the clinical application of FMT in cancer immunotherapy. In a phase II study, a total of 20 MSS mCRC patients were enrolled and received FMT combined with trastuzumab and furosemide as third line or above treatment. The median PFS was 9.6 months (95% CI 4.1-15.1) and the median OS was 13.7 months (95% CI 9.3-17.7), with controllable side effects, demonstrating the potential of FMT in the field of rectal cancer.

Conditions

• Localized Advanced Rectal Adenocarcinoma

Interventions

Type	Name	Description
DRUG	Sintilimab plus Chemotherapy	All patients received standard long-term radiation therapy (LCRT) (50.0Gy/25f) and concurrent chemotherapy with capecitabine (825 mg/m2, bid, po) (Phase 1); Xelox scheme (Oxaliplatin 130 mg/m2, ivgtt ，d1； Capecitabine 1000 mg/m2, bid，d1-14) (Phase 2); . During the radiotherapy and chemotherapy period, they also received two cycles of immunotherapy with Sintilimab (200mg, ivgtt, d1, q3w).
DRUG	Intestinal microbiota capsules	During Phase 1, intestinal microbiota transplantation treatment, oral intestinal microbiota capsules are used for transplantation treatment, with a dose of 30 capsules/day (about 1U sediment microbiota, containing about 1 × 1013 bacteria). Transplantation is carried out continuously for 3 days starting from each week, for a total of 3 courses of treatment.
RADIATION	Standard Long Course Radiotherapy	50.0Gy/25f
PROCEDURE	Total mesorectal excision	6-8 weeks after the end of the first phase and combined with 5 cycles of Xelox regimen adjuvant chemotherapy.

Timeline

• Start date: 2025-03-01
• Primary completion: 2026-03-01
• Completion: 2028-08-01
• First posted: 2025-04-17
• Last updated: 2025-04-17

Locations

1 site across 1 country: China