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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| yFMT + PD-1 Inhibitor + FOLFIRI Group | Experimental | This study evaluates a combined intervention of young-donor fecal microbiota transplantation (yFMT), PD-1 inhibitor immunotherapy, and FOLFIRI chemotherapy for microsatellite stable metastatic colorectal cancer (MSS mCRC) patients. yFMT (6 sessions every 2 weeks via nasogastric tube or oral capsules) aims to modulate the gut microbiome and enhance immune response, administered concurrently with weight-based PD-1 inhibitor and FOLFIRI regimen (fluorouracil, leucovorin, irinotecan) synchronized every 2 weeks. This 3-month treatment period, followed by 9-month follow-up, tests the hypothesis that yFMT synergistically improves immunotherapy efficacy through microbiome alteration. Patients are closely monitored for adverse events with prompt management and regimen adjustments to ensure safety. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| yFMT | Drug | 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, followed by 9-month follow-up. Safety monitoring includes prompt adverse event management and regimen adjustments as needed. |
| Measure | Description | Time Frame |
|---|---|---|
| The incidence of serious adverse events (SAEs) | The proportion of patients experiencing serious adverse events (Grade ≥3 per CTCAE v5.0) during the treatment and follow-up period, including events related to yFMT, immunotherapy, or chemotherapy that result in death, life-threatening conditions, hospitalization, or persistent disability. | From the initiation of yFMT treatment to the completion of follow-up |
| treatment-related adverse events (TRAEs) | The incidence of adverse events assessed as related to the study intervention (yFMT, PD-1 inhibitor, or FOLFIRI regimen) by the investigator, graded according to CTCAE v5.0, occurring from treatment initiation through the follow-up period. | From the initiation of yFMT treatment to the completion of follow-up |
| the rate of intervention adjustments due to adverse events | The proportion of patients requiring dose reduction, treatment interruption, or discontinuation of yFMT, immunotherapy, or chemotherapy due to treatment-related adverse events, documented with reasons and duration of adjustments. | From the initiation of yFMT treatment to the completion of follow-up |
| Measure | Description | Time Frame |
|---|---|---|
| PFS | Progression-free survival, defined as the time from treatment initiation to radiographic disease progression (per RECIST v1.1) or death from any cause, whichever occurs first. | From treatment initiation to radiographic disease progression (per RECIST v1.1) or death from any cause, whichever occurs first. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Qingqi Hong, MD | Contact | 15980809201 | hqqsums@aliyun.com | |
| Hongfei Huang | Contact | 15159672193 | 1378498011@qq.com |
| Name | Affiliation | Role |
|---|---|---|
| Qingqi Hong, MD | The First Affiliated Hospital of Xiamen University | Principal Investigator |
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| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 38572751 | Result | 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. | |
| 38160327 | Result | 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 cancer, 2023. Cancer Commun (Lond). 2024 Jan;44(1):127-172. doi: 10.1002/cac2.12516. Epub 2023 Dec 31. |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP_ICF | Yes | Yes | Yes | Study Protocol, Statistical Analysis Plan, and Informed Consent Form | Feb 26, 2026 | Mar 14, 2026 | Prot_SAP_ICF_000.pdf |
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| ID | Term |
|---|---|
| D000082082 | Immune Checkpoint Inhibitors |
| ID | Term |
|---|---|
| D045504 | Molecular Mechanisms of Pharmacological Action |
| D020228 | Pharmacologic Actions |
| D020164 | Chemical Actions and Uses |
| D000074322 | Antineoplastic Agents, Immunological |
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Intervention: Young-donor fecal microbiota transplantation (yFMT) combined with PD-1 inhibitor immunotherapy and FOLFIRI chemotherapy for MSS mCRC patients.
yFMT: 6 sessions every 2 weeks (nasogastric tube or oral capsules) using fecal microbiota from young donors to modulate gut microbiome and enhance immune response.
Immunotherapy: Weight-based PD-1 inhibitor to block the PD-1 pathway. Chemotherapy: FOLFIRI regimen (fluorouracil, leucovorin, irinotecan) every 2 weeks, synchronized with yFMT.
Rationale: Synergistic approach where yFMT may improve immunotherapy efficacy by altering gut microbiome to enhance anti-tumor immune response.
Duration: 3-month treatment period followed by 9-month follow-up. Safety: Close monitoring for adverse events with prompt management and regimen adjustments as needed.
Objective: Explore yFMT's potential to enhance immunotherapy and chemotherapy effectiveness in MSS mCRC.
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| ORR |
Objective response rate, defined as the proportion of patients achieving complete response (CR) or partial response (PR) as assessed by investigators according to RECIST v1.1 criteria. |
| 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 | Overall survival, defined as the time from treatment initiation to death from any cause. | From treatment initiation until death (any cause) or last known alive date, up to 12 months. |
| 29097493 | Result | 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, McAllister F, Marcelo Riquelme Sanchez E, Zhang Y, Le Chatelier E, Zitvogel L, Pons N, Austin-Breneman JL, Haydu LE, Burton EM, Gardner JM, Sirmans E, Hu J, Lazar AJ, Tsujikawa T, Diab A, Tawbi H, Glitza IC, Hwu WJ, Patel SP, Woodman SE, Amaria RN, Davies MA, Gershenwald JE, Hwu P, Lee JE, Zhang J, Coussens LM, Cooper ZA, Futreal PA, Daniel CR, Ajami NJ, Petrosino JF, Tetzlaff MT, Sharma P, Allison JP, Jenq RR, Wargo JA. Gut microbiome modulates response to anti-PD-1 immunotherapy in melanoma patients. Science. 2018 Jan 5;359(6371):97-103. doi: 10.1126/science.aan4236. Epub 2017 Nov 2. |
| 26541606 | Result | 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. |
| 38024475 | Result | 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. |
| 37143538 | Result | 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. |
| 35748749 | Result | 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. |
| 41300985 | Result | 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. |
| 39909032 | Result | Zhu X, Hu M, Huang X, Li L, Lin X, Shao X, Li J, Du X, Zhang X, Sun R, Tong T, Ma Y, Ning L, Jiang Y, Zhang Y, Shao Y, Wang Z, Zhou Y, Ding J, Zhao Y, Xuan B, Zhang H, Zhang Y, Hong J, Fang JY, Xiao X, Shen B, He S, Chen H. Interplay between gut microbial communities and metabolites modulates pan-cancer immunotherapy responses. Cell Metab. 2025 Apr 1;37(4):806-823.e6. doi: 10.1016/j.cmet.2024.12.013. Epub 2025 Feb 4. |
| D000970 | Antineoplastic Agents |
| D045506 | Therapeutic Uses |