Fecal Microbiota Transplantation for Preventing Gastrointestinal Symptoms in Extrapulmonary Neuroendocrine Neoplasms: A Real-World Study (FMT-NENs)

Existing studies have demonstrated that patients with different types of tumors exhibit significant increases in Enterobacter and Staphylococcus genera, along with marked decreases in Lactobacillus, Bacteroides, Bifidobacterium, and Enterococcus genera in their feces following chemotherapy. Research reports indicate a significant decline in bacterial diversity in rectal cancer patients post-chemotherapy, particularly showing reduced abundances of Porphyromonas, Peptostreptococcus, and Veillonella. Motoori et al. found that esophageal cancer patients undergoing combined chemotherapy with 5-FU, cisplatin, and docetaxel experienced significant reductions in intestinal Lactobacillus, alongside notable increases in Clostridium difficile and Enterococcus. Iida et al. confirmed that gut microbiota enhances the therapeutic efficacy of platinum-based agents and CpG oligonucleotides in cancer treatment. Concurrent studies suggest that probiotic supplementation during chemotherapy alleviates chemotherapy-related gastrointestinal reactions. Fecal microbiota transplantation (FMT), which involves transferring functional microbiota from healthy donors to patients' gastrointestinal tracts to reconstruct gut microbiota and improve microbial homeostasis, has emerged as a key clinical approach for regulating gut dysbiosis. It is currently recognized as the most effective established therapy for recurrent Clostridioides difficile infection (CDI). Previous studies have indicated FMT as a relatively safe, effective, and recommended treatment modality, while providing theoretical and experimental foundations for elucidating its efficacy and safety in preventing/reducing gastrointestinal symptoms associated with digestive tract cancer therapies.

This study aims to evaluate the improvement of treatment-related gastrointestinal symptoms and safety profile of FMT in extrapulmonary neuroendocrine tumor patients.

Study Overview

• Status: Not yet recruiting
• Conditions: Treatment-related Gastrointestinal Toxicity (Including Diarrhea, Constipation, Nausea, and Vomiting); Extrapulmonary Neuroendocrine Neoplasms
• Intervention / Treatment: Procedure: Fecal Microbiota Transplant (FMT); Other: Standard Therapy

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Zhejiang
    • Hangzhou, Zhejiang, China
      • Second Affiliated Hospital, School of Medicine, Zhejiang University
      • Contact: Wen Cai

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age ≥18 years, regardless of gender;
2. Anticipated survival period ≥3 months;
3. Pathologically confirmed diagnosis of extrapulmonary neuroendocrine neoplasms;
4. Development of gastrointestinal adverse reactions (including but not limited to diarrhea, constipation, vomiting, nausea, etc.) within three cycles of standard treatment;
5. Patients are capable and willing to sign an informed consent form and complete follow-up;
6. Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) score of 1-3;
7. No use of oral/intravenous broad-spectrum antibiotics within 3 days prior to enrollment;
8. Ability to swallow capsules without chewing;
9. Adequate organ function confirmed by screening laboratory tests.

Exclusion Criteria:

1. Patients with major organ dysfunction or failure, including but not limited to cardiac insufficiency/heart failure, renal insufficiency/failure, or hepatic insufficiency/failure;
2. Uncontrolled or severe infection;
3. Known history of psychotropic drug abuse, alcoholism, or substance abuse;
4. Severe infection accompanied by sepsis or septicemia;
5. History of severe allergic reactions or known allergy to components of the liquid live bacterial enteric-coated capsules;
6. Female subjects with a positive pregnancy test, lactating women, or women of childbearing potential who refuse to use contraceptive measures during the observation period (15 weeks);
7. Patients with gastrointestinal perforation and/or fistula;
8. Other conditions deemed unsuitable for enrollment by the investigator.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Fecal microbiota transplantation; Fecal Microbiota Transplantation (FMT) is delivered as a single dose of oral microbiota capsules within 72 hours before starting standard therapy.	Procedure: Fecal Microbiota Transplant (FMT); Fecal Microbiota Transplantation (FMT) is delivered as a single dose of oral microbiota capsules within 72 hours before starting standard therapy.
Active Comparator: Control; Standard Therapy Alone	Other: Standard Therapy; Standard Therapy Alone

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Improvement in treatment-related gastrointestinal symptoms	Hart Diarrhea Score	Assessed every two cycles (6 weeks)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Chemotherapy cycle delay rate		Assessed every two cycles (6 weeks)
Quality of Life (QoL) assessment	QOL assessment	Assessed every two cycles (6 weeks)
Gut microbiota colonization	Performing 16S rRNA sequencing, metagenomic sequencing on the samples.	Assessed every two cycles (6 weeks)

Collaborators and Investigators

• Sponsor: Second Affiliated Hospital, School of Medicine, Zhejiang University

Study record dates

Study Major Dates

• Study Start (Estimated): May 1, 2025
• Primary Completion (Estimated): December 31, 2028
• Study Completion (Estimated): December 31, 2028

Study Registration Dates

• First Submitted: April 6, 2025
• First Submitted That Met QC Criteria: April 6, 2025
• First Posted (Actual): April 11, 2025

Study Record Updates

• Last Update Posted (Actual): April 11, 2025
• Last Update Submitted That Met QC Criteria: April 6, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Signs and Symptoms, Digestive; Neoplasms by Histologic Type; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neoplasms; Neuroendocrine Tumors; Vomiting; Constipation; Diarrhea
• Other Study ID Numbers: 2025-0198

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No