Inactivated Bacteroides Fragilis for Prevention of Chemotherapy-Induced Diarrhea

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).

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 initial 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 that, in the investigator's opinion, would preclude subsequent efficacy evaluation; 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 or PD-1 antibodies other than the chemotherapy/treatment regimen specified in the protocol during the trial.
4. Concurrent abdominopelvic radiotherapy during the trial period; or unresolved radiotherapy-induced enteritis caused by previous abdominopelvic radiotherapy.
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, including temporary stomas that have not been closed or patients whose bowel function has not recovered after stoma closure.
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.