The research protocol for the study titled "Exploratory Study of Early Life Fecal Microbiota Transplantation (yFMT) Combined with Immunotherapy and Chemotherapy in Microsatellite Stable Metastatic Colorectal Cancer (MSS mCRC)" is designed to investigate a novel treatment approach for patients with MSS mCRC, a group that typically does not respond well to immunotherapy. The study is being conducted at the Gastrointestinal Tumor Surgery Department of the First Affiliated Hospital of Xiamen University.
Objectives:
Primary Objective: To evaluate the safety of combining yFMT with immunotherapy (PD-1 inhibitor) and chemotherapy (FOLFIRI) in patients with MSS mCRC.
Secondary Objectives: To explore the efficacy of the combined treatment in terms of progression-free survival (PFS), objective response rate (ORR), and overall survival (OS), as well as to assess the impact of yFMT on the patients' immune microenvironment and its potential synergistic effects with immunotherapy and chemotherapy.
Study Design:
The study is a single-center, single-arm trial with a total of 10 participants. The study timeline includes a screening period of 2 weeks, a treatment period of 3 months, and a follow-up period of 9 months.
Participants:
The study will enroll 10 patients aged between 18 and 75 years, regardless of gender.
Inclusion criteria
Patients must have a confirmed diagnosis of MSS mCRC, must have experienced disease progression after first-line chemotherapy and targeted therapy, and must have an ECOG performance status of 0-1.
Exclusion criteria
Patients with a history of FMT, severe organ dysfunction (heart, lung, liver, kidney), other malignancies, psychiatric disorders, pregnancy or lactation, and those unable to provide informed consent will be excluded.
Interventions:
Participants will receive yFMT every two weeks for a total of six sessions, along with PD-1 inhibitor immunotherapy and FOLFIRI chemotherapy.
Endpoints:
Primary Endpoints: The incidence of serious adverse events (SAEs), treatment-related adverse events (TRAEs), and the rate of intervention adjustments due to adverse events.
Secondary Endpoints: PFS, ORR, and OS.
Statistical Analysis:
Descriptive statistics will be used to calculate the incidence rates and 95% confidence intervals for primary endpoints.
Kaplan-Meier methods will be used for secondary endpoints to estimate survival functions and calculate median survival times with 95% confidence intervals.
Duration:
The study is expected to last for approximately two years from the initiation of the study to the completion of data analysis.
Research Team:
The project is led by Principal Investigator Dr. Hong Qingqi, who is a Chief Physician. The team includes a multidisciplinary group of professionals, including other physicians, nurses, and researchers, all of whom have received Good Clinical Practice (GCP) training.
Ethical Considerations:
The study will adhere to the principles of the Declaration of Helsinki and will be approved by the hospital's ethics committee before initiation.
Informed consent will be obtained from all participants or their legal representatives.
Data Management:
All data will be collected, managed, and stored in accordance with GCP guidelines and relevant regulations to ensure confidentiality and integrity.
This study aims to provide a comprehensive evaluation of the safety and potential benefits of yFMT in combination with immunotherapy and chemotherapy for MSS mCRC, potentially offering a new treatment paradigm for this challenging disease.
