Inactivated Bacteroides Fragilis for Prevention of Chemotherapy-Induced Diarrhea

The incidence of chemotherapy-induced diarrhea (CID) is closely related to the types of anticancer drugs. Combination chemotherapy regimens such as fluorouracil derivatives and irinotecan, as well as tyrosine kinase inhibitors like neratinib, are associated with a high severity and incidence of diarrhea. These All antineoplastic agents can induce intestinal epithelial cell apoptosis, damage the intestinal mucosa, subsequently reduce the absorption surface area, and thereby lead to diarrhea. Recent literature has indicated that Bacteroides fragilis may be a candidate drug for the treatment and prevention of CID. This study intends to conduct a randomized controlled trial to determine the efficacy and mechanism of action of inactivated Bacteroides fragilis (SK10) in the prevention of chemotherapy-induced diarrhea (CID).

Study Overview

• Status: Not yet recruiting
• Conditions: Chemotherapy-induced Diarrhea
• Intervention / Treatment: Drug: Placebo; Drug: Inactivated Bacteroides fragilis

• Study Type: Interventional
• Enrollment (Estimated): 200
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Voluntarily sign the informed consent form, be able to comply with the protocol and have the capacity to complete relevant procedures.
2. Aged ≥ 18 years old (based on the date of signing the ICF), regardless of gender.
3. Patients with malignant tumors confirmed by pathology or cytology.

4. Patients scheduled to receive the following first-line treatments at the standard dose specified in the protocol:

   • Cohort 1: Patients with advanced colorectal cancer receiving the FOLFIRI regimen (irinotecan + fluorouracil + leucovorin);
   • Cohort 2: Patients with breast cancer receiving neratinib treatment.
5. ECOG performance status score of 0-1 at the start of the study.
6. Expected survival time ≥ 12 weeks.
7. Subjects of childbearing potential (including males and females) agree to adopt effective contraceptive measures approved by the investigators (e.g., intrauterine device, contraceptive pills or condoms) during the trial and within 3 months after the trial ends. Female subjects of childbearing potential must have a negative result in serum human chorionic gonadotropin (hCG) test.

Exclusion Criteria:

1. History of altered bowel habits or abnormal stool characteristics prior to screening; or use of laxatives within 7 days prior to randomization; or use of antidiarrheal agents within 48 hours prior to randomization.
2. Complicated with diseases causing diarrhea, including but not limited to inflammatory bowel disease (e.g., ulcerative colitis and Crohn's disease), suspected or confirmed infectious diarrhea, irritable bowel syndrome, celiac disease, etc.
3. Receipt of any chemotherapeutic agents, cetuximab or PD-1 antibodies other than the chemotherapy/treatment regimen specified in the protocol during the trial.
4. Previous or concurrent abdominopelvic radiotherapy during the trial period.
5. Medical history of chronic use of laxatives (≥ 30 non-consecutive days).
6. Need for antibiotic treatment during the trial or long-term use of antibiotics prior to randomization.
7. Patients with stomas (temporary stomas should be closed for at least 6 months prior to randomization).
8. Presence of unhealed surgical wounds, ulcers or fractures.
9. Known history of human immunodeficiency virus (HIV) infection (positive HIV antibody test).
10. History of allergy or suspected allergy to antidiarrheal drugs (e.g., loperamide and its components).
11. Suspected or confirmed history of alcohol or drug abuse.
12. Pregnant or lactating women.
13. Concurrent participation in other clinical trials.
14. Other conditions deemed inappropriate for study participation by the investigator.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm 1; Trial Group of Patients with Advanced Colorectal Cancer	Drug: Inactivated Bacteroides fragilis; Live Biotherapeutic Products; Other Names: SK10
Placebo Comparator: Arm 2; Control Group of Patients with Advanced Colorectal Cancer	Drug: Placebo; Placebo
Experimental: Arm 3; Trial Group of Patients with Breast Cancer	Drug: Inactivated Bacteroides fragilis; Live Biotherapeutic Products; Other Names: SK10
Placebo Comparator: Arm 4; Control Group of Patients with Breast Cancer	Drug: Placebo; Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Incidence of Diarrhea	Proportion of Patients with Any Grade of Diarrhea assessed by CTCAE v5.0	4 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Grade ≥2 Diarrhea	Proportion of Patients with Grade 2 or Higher Diarrhea assessed by CTCAE v5.0	4 weeks
Incidence of Grade ≥3 Diarrhea	Proportion of Patients with Grade 2 or Higher Diarrhea assessed by CTCAE v5.0	4 weeks
Days of Diarrhea	Mean Days of Diarrhea per Treatment Cycle	4 weeks
Frequency of Diarrhea	Mean Frequency of Stool Type 6 or 7 per Treatment Cycle	4 weeks
Percentage and Days of Patients Receiving Antidiarrheal Treatment	Percentage of patients treated with antidiarrheal drugs (loperamide, diphenoxylate, octreotide, montmorillonite), defined as the proportion of patients with at least one dose of antidiarrheal drugs relative to the total number of cases; days of antidiarrheal treatment, defined as the mean days of antidiarrheal drug administration per treatment cycle.	4 weeks
Proportion of Patients Who Received Medical Treatment for Diarrhea	Proportion of patients who sought medical attention due to diarrhea and received intravenous fluid replacement or anti-infective treatment from investigators.	4 weeks
Proportion of Patients Who Had Chemotherapy/Treatment Dose Reduction, Delay or Discontinuation Due to Diarrhea	Proportion of patients with chemotherapy/treatment dose reduction, delay or discontinuation as judged by investigators due to diarrhea.	4 weeks
Relative Dose Intensity of Chemotherapy/Treatment	Ratio of delivered dose intensity (mg/m² or mg) to planned dose intensity (mg/m² or mg)	4 weeks
Incidence of Other Gastrointestinal Symptoms	Proportion of patients with at least one episode of any grade of gastrointestinal symptoms (constipation, abdominal distension, abdominal pain, hematochezia, nausea, vomiting) assessed by CTCAE v5.0.	4 weeks
Change in Quality of Life Score of Cancer Patients Compared with Baseline	Defined as the change in the QLQ-C30 quality of life scale score of cancer patients after study intervention compared with the baseline.	4 weeks
Incidence of Adverse Event (AE)	Proportion of participants with adverse events as assessed by CTCAE v5.0	4 weeks
Incidence of Serious Adverse Event (SAE)	Proportion of participants with Serious Adverse Event (SAE) as assessed by GCP 2020	4 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Levels of Blood Inflammatory Cytokines Compared with Baseline	Blood inflammatory cytokines Including but not limited to TNF-α, IL-6, IL-1β, IL-4, IL-10, IL-11, etc. Change in Levels of Blood Inflammatory Cytokines Compared with Baseline defined as the change in the levels of blood inflammatory cytokines of cancer patients after study intervention compared with the baseline.	4 weeks
Change in Composition and Diversity of Fecal Flora Structure, and Change in Fecal Metabolomics	Change in Composition and Diversity of Fecal Flora Structure defined as the change in the composition and diversity of fecal flora structure of cancer patients after study intervention compared with the baseline. Change in Fecal Metabolomics defined as the change in the fecal metabolomics of cancer patients after study intervention compared with the baseline.	4 weeks

Collaborators and Investigators

• Sponsor: Shenzhen Hospital of Southern Medical University

Study record dates

Study Major Dates

• Study Start (Estimated): December 15, 2025
• Primary Completion (Estimated): March 30, 2026
• Study Completion (Estimated): March 30, 2026

Study Registration Dates

• First Submitted: December 12, 2025
• First Submitted That Met QC Criteria: December 28, 2025
• First Posted (Actual): December 30, 2025

Study Record Updates

• Last Update Posted (Actual): December 30, 2025
• Last Update Submitted That Met QC Criteria: December 28, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Other Study ID Numbers: SK10-IIT

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No