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

NCT06931808 | Enrolling By Invitation Phase 4

• 1 other identifier: KY-XM-038
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Localized Advanced Rectal Adenocarcinoma

Keywords

mid-low position; IIA-IIIC (T3-4/N+)

Outcome Measures

Primary Outcomes (7)

• pathologic complete response rate

  Defined as the percentage of subjects with ypT0N0 who have no residual tumor cells in the primary tumor and lymph nodes after surgery compared to all subjects.

  Up to 12 weeks

• Overall Survival

  The percentage of subjects who are still alive after 3 years of follow-up among all subjects.

  Three years after the end of treatment

• R0 resection rate

  Defined as the complete resection rate of tumors with negative margins removed under a microscope

  During the surgery

• Tumor regression grading

  According to AJCC 8th edition, the Tumor regression grading is based on the proportion of fibrosis and residual tumors in the tumor. Grade 0 indicates complete regression of the tumor, Grade 1 indicates regression of over 90%, Grade 2 indicates regression between 10% and 90%, Grade 3 indicates regression of less than 10%, and Grade 4 indicates no significant regression of the tumor

  During the surgery

• Completion rate of neoadjuvant therapy

  Defined as the percentage of subjects who have completed all neoadjuvant therapies compared to all subjects

  Up to 6 weeks

• Event free survival rate

  The percentage of subjects who were followed up for 3 years and still survived without disease recurrence or change of treatment plan among all subjects.

  Three years after the end of treatment

• Disease-free survival rate

  The percentage of subjects who were followed up for 3 years and still survived without disease recurrence among all subjects.

  Three years after the end of treatment

Study Arms (1)

Intestinal microbiota transplantation combined with chemoradiotherapy and Sintilimab

EXPERIMENTAL

Intestinal microbiota transplantation combined with synchronous radiotherapy, chemotherapy, and Sintilimab as neoadjuvant therapy

Drug: Sintilimab plus Chemotherapy; Drug: Intestinal microbiota capsules; Radiation: Standard Long Course Radiotherapy; Procedure: Total mesorectal excision

Interventions

Sintilimab plus Chemotherapy DRUG

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).

Intestinal microbiota transplantation combined with chemoradiotherapy and Sintilimab

Intestinal microbiota capsules DRUG

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.

Intestinal microbiota transplantation combined with chemoradiotherapy and Sintilimab

Standard Long Course Radiotherapy RADIATION

50.0Gy/25f

Intestinal microbiota transplantation combined with chemoradiotherapy and Sintilimab

Total mesorectal excision PROCEDURE

6-8 weeks after the end of the first phase and combined with 5 cycles of Xelox regimen adjuvant chemotherapy.

Intestinal microbiota transplantation combined with chemoradiotherapy and Sintilimab

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may not qualify if:

• \. Other malignant tumors, including rectal cancer with other pathological types within 5 years; 2. Not using probiotics in the past 2 months; 3. Severe damage to the intestinal barrier, such as sepsis, active gastrointestinal bleeding, perforation, etc.; 4. Weight loss of ≥ 20% within 90 days; 5. Poor nutritional status or PG-SGA score ≥ 9; 6. Severe and/or uncontrolled illnesses.
• Poor blood pressure control (systolic blood pressure ≥ 150mmHg or diastolic blood pressure ≥ 100mmHg)
• ≥ grade 2 myocardial ischemia or myocardial infarction, arrhythmia (QTc ≥ 470ms), and ≥ grade 2 congestive heart failure
• History of interstitial lung disease, non infectious pneumonia, pulmonary fibrosis, or other uncontrolled acute lung diseases
• Active or uncontrolled severe infection (≥ CTCAE level 2 infection)
• Active syphilis patients
• Renal failure requiring hemodialysis or peritoneal dialysis
• History of immunodeficiency, including HIV positivity or other acquired or congenital immunodeficiency diseases, or organ transplantation 7. Poor control of diabetes (fasting blood glucose \[FBG\]\>10mmol/L) 8. Significant surgical treatment, open biopsy, or significant traumatic injury within 60 days prior to the start of treatment; Or long-term untreated wounds or fractures 9. Serious arterial/venous thrombotic events such as cerebrovascular accidents (including temporary ischemic attacks, cerebral hemorrhage, cerebral infarction), deep vein thrombosis, and pulmonary embolism occurred within 6 months before the start of treatment 10. History of abuse of psychotropic drugs who are unable to quit or have mental disorders 11. History of severe allergies 12. Pregnant or lactating women

Sponsors & Collaborators

• First Affiliated Hospital of Ningbo University: lead

Study Sites (1)

First Affiliated Hospital of Ningbo University

Ningbo, Zhejiang, 315000, China

Location

MeSH Terms

Interventions

sintilimab; Drug Therapy; Gastrointestinal Microbiome

Intervention Hierarchy (Ancestors)

Therapeutics; Microbiota; Microbiological Phenomena; Biota; Biodiversity; Ecosystem; Environment; Ecological and Environmental Phenomena; Biological Phenomena; Environment and Public Health

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NETWORK
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: chief physician

Study Record Dates

• First Submitted: March 15, 2025
• First Posted: April 17, 2025
• Study Start: March 1, 2025
• Primary Completion: March 1, 2026
• Study Completion (Estimated): August 1, 2028
• Last Updated: April 17, 2025

Record last verified: 2025-04

Locations

CN (1)