Using Healthy Gut Bacteria to Boost Immune Treatment for Advanced Bowel Cancer

Official title

An Exploratory Study of Fecal Microbiota Transplantation (FMT) Combined With Immunotherapy and Chemotherapy in Microsatellite Stable Metastatic Colorectal Cancer (MSS mCRC)

Overview

This research protocol outlines an exploratory study on the combination of early-life fecal microbiota transplantation (yFMT) with immunotherapy and chemotherapy in patients with microsatellite stable metastatic colorectal cancer (MSS mCRC). The single-center, single-arm study aims to assess the safety of yFMT in conjunction with immunotherapy and chemotherapy, with a secondary focus on exploring its efficacy and impact on the patients' immune microenvironment. The study will enroll 10 patients aged 18-75 who have progressed after first-line chemotherapy and targeted therapy. The intervention involves six sessions of yFMT every two weeks, alongside PD-1 inhibitor immunotherapy and FOLFIRI chemotherapy. The primary endpoints are the incidence of serious adverse events (SAEs), treatment-related adverse events (TRAEs), and intervention adjustments due to adverse events, while secondary endpoints include progression-free survival (PFS), objective response rate (ORR), and overall survival (OS). The study is expected to last two years from initiation to data analysis completion, and it will be conducted at the Gastrointestinal Tumor Surgery Department of the First Affiliated Hospital of Xiamen University.

Detailed description

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.

Interventions

• Drug yFMT
  This study evaluates a triple-combination therapy for MSS mCRC comprising: (1) yFMT (6 biweekly sessions via nasogastric tube or oral capsules using young-donor fecal microbiota to modulate gut microbiome); (2) weight-based PD-1 inhibitor immunotherapy; and (3) FOLFIRI chemotherapy (fluorouracil, leucovorin, irinotecan) synchronized biweekly with yFMT. The 3-month treatment period tests the hypothesis that yFMT enhances immunotherapy efficacy through microbiome-mediated immune modulation, follow

Primary outcome measures

• The incidence of serious adverse events (SAEs) [Time frame: From the initiation of yFMT treatment to the completion of follow-up]
• treatment-related adverse events (TRAEs) [Time frame: From the initiation of yFMT treatment to the completion of follow-up]
• the rate of intervention adjustments due to adverse events [Time frame: From the initiation of yFMT treatment to the completion of follow-up]

Secondary outcome measures (3)

• PFS [Time frame: From treatment initiation to radiographic disease progression (per RECIST v1.1) or death from any cause, whichever occurs first.]
• ORR [Time frame: Objective response will be assessed every 6-8 weeks from the initiation of yFMT treatment until disease progression, death, or completion of 12-month study period (3-month treatment + 9-month follow-up), whichever occurs first.]
• OS [Time frame: From treatment initiation until death (any cause) or last known alive date, up to 12 months.]

Eligibility criteria

Inclusion criteria

• Histologically or cytologically confirmed diagnosis of MSS mCRC
• Experienced disease progression after first-line chemotherapy and targeted therapy
• ECOG performance status of 0-1

Exclusion criteria

• History of FMT
• Severe organ dysfunction (heart, lung, liver, kidney)
• Other malignancies, psychiatric disorders, pregnancy or lactation
• Unable to provide informed consent

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Other

Study locations

Center list to be confirmed — check the primary protocol.

Publications

• Bray F, Laversanne M, Sung H, Ferlay J, Siegel RL, Soerjomataram I, Jemal A. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2024 May-Jun;74(3):229-263. doi: 10.3322/caac.21834. Epub 2024 Apr 4. PMID 38572751
• Wang FH, Zhang XT, Tang L, Wu Q, Cai MY, Li YF, Qu XJ, Qiu H, Zhang YJ, Ying JE, Zhang J, Sun LY, Lin RB, Wang C, Liu H, Qiu MZ, Guan WL, Rao SX, Ji JF, Xin Y, Sheng WQ, Xu HM, Zhou ZW, Zhou AP, Jin J, Yuan XL, Bi F, Liu TS, Liang H, Zhang YQ, Li GX, Liang J, Liu BR, Shen L, Li J, Xu RH. The Chinese Society of Clinical Oncology (CSCO): Clinical guidelines for the diagnosis and treatment of gastric PMID 38160327
• Gopalakrishnan V, Spencer CN, Nezi L, Reuben A, Andrews MC, Karpinets TV, Prieto PA, Vicente D, Hoffman K, Wei SC, Cogdill AP, Zhao L, Hudgens CW, Hutchinson DS, Manzo T, Petaccia de Macedo M, Cotechini T, Kumar T, Chen WS, Reddy SM, Szczepaniak Sloane R, Galloway-Pena J, Jiang H, Chen PL, Shpall EJ, Rezvani K, Alousi AM, Chemaly RF, Shelburne S, Vence LM, Okhuysen PC, Jensen VB, Swennes AG, McAll PMID 29097493
• Sivan A, Corrales L, Hubert N, Williams JB, Aquino-Michaels K, Earley ZM, Benyamin FW, Lei YM, Jabri B, Alegre ML, Chang EB, Gajewski TF. Commensal Bifidobacterium promotes antitumor immunity and facilitates anti-PD-L1 efficacy. Science. 2015 Nov 27;350(6264):1084-9. doi: 10.1126/science.aac4255. Epub 2015 Nov 5. PMID 26541606
• Zhao W, Lei J, Ke S, Chen Y, Xiao J, Tang Z, Wang L, Ren Y, Alnaggar M, Qiu H, Shi W, Yin L, Chen Y. Fecal microbiota transplantation plus tislelizumab and fruquintinib in refractory microsatellite stable metastatic colorectal cancer: an open-label, single-arm, phase II trial (RENMIN-215). EClinicalMedicine. 2023 Nov 14;66:102315. doi: 10.1016/j.eclinm.2023.102315. eCollection 2023 Dec. PMID 38024475
• Yu H, Li XX, Han X, Chen BX, Zhang XH, Gao S, Xu DQ, Wang Y, Gao ZK, Yu L, Zhu SL, Yao LC, Liu GR, Liu SL, Mu XQ. Fecal microbiota transplantation inhibits colorectal cancer progression: Reversing intestinal microbial dysbiosis to enhance anti-cancer immune responses. Front Microbiol. 2023 Apr 18;14:1126808. doi: 10.3389/fmicb.2023.1126808. eCollection 2023. PMID 37143538
• Davar D, Zarour HM. Facts and Hopes for Gut Microbiota Interventions in Cancer Immunotherapy. Clin Cancer Res. 2022 Oct 14;28(20):4370-4384. doi: 10.1158/1078-0432.CCR-21-1129. PMID 35748749
• De Lucia SS, Nista EC, Candelli M, Archilei S, Deutschbein F, Capuano E, Gasbarrini A, Franceschi F, Pignataro G. Microbiota and Pancreatic Cancer: New Therapeutic Frontiers Between Engineered Microbes, Metabolites and Non-Bacterial Components. Cancers (Basel). 2025 Nov 10;17(22):3618. doi: 10.3390/cancers17223618. PMID 41300985

Identifiers

NCT: NCT07486492 · XMYY-2026KY036

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗