Probiotics for Prevention of Neratinib-Induced Diarrhea in Breast Cancer Patients

NCT06892093 | Recruiting

• 1 other identifier: SYSKY-2025-105-02
• Study Type: interventional
• Target: 308
• Locations: 1 country
• Sites: 1

Brief Summary

This study aims to evaluate the efficacy and safety of probiotics for the prevention of diarrhea in patients with breast cancer receiving the tyrosine kinase inhibitor (TKI) Neratinib. Study Design: This is a prospective, randomized controlled clinical trial. Participants will be randomly assigned to either a probiotics intervention group or a placebo-controlled group. Both groups will receive prophylactic loperamide according to the FDA-recommended dosing schedule for neratinib-associated diarrhea. Primary Objective: To evaluate the efficacy of probiotics in reducing the incidence and severity of diarrhea in patients receiving Neratinib. Secondary Objectives: This study will also investigate the effects of probiotics on gut microbiota composition and their potential impact on drug efficacy. Study Duration: Enrollment is planned from August 2025 to June 2027 at Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University. Both the intervention and control groups will receive treatment for a total of six weeks (two cycles of three weeks each). No post-treatment observation period is included. Eligibility Criteria: Participants must be diagnosed with HER2-positive breast cancer and scheduled to receive Neratinib. Exclusion criteria include patients with severe gastrointestinal disorders or recent probiotic consumption.

Conditions

HER2-positive Breast Cancer; Diarrhea Caused by Drug; Neratinib

Keywords

Neratinib; Probiotics; Diarrhea; Breast Cancer

Outcome Measures

Primary Outcomes (1)

• Incidence of Grade ≥3 Diarrhea

  The incidence of grade 3 or higher diarrhea during the 6-week treatment period, assessed using the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.

  Up to 6 weeks

Secondary Outcomes (9)

• Incidence of Any Grade Diarrhea

  Up to 6 weeks

• Duration of First Episode of Grade 3 Diarrhea

  Up to 6 weeks

• Proportion of Participants Hospitalized Due to Diarrhea

  Up to 6 weeks

• Loperamide Usage Patterns

  Up to 6 weeks

• Change from Baseline in Overall Quality of Life Assessed by EORTC QLQ-C30

  Baseline, Weeks 2, 4, and 6 (End of Study)

Other Outcomes (2)

• Gut Microbiota Composition Changes

  Baseline, Week 3, and Week 6

• Correlation Analysis of Gut Microbiota-Metabolite-Immune Axis

  Baseline, Week 3, and Week 6

Study Arms (2)

Probiotics + Neratinib + Loperamide

EXPERIMENTAL

Dietary Supplement: Probiotics; Drug: Loperamide

Placebo + Neratinib + Loperamide

PLACEBO COMPARATOR

Dietary Supplement: Placebo; Drug: Loperamide

Interventions

Probiotics DIETARY_SUPPLEMENT

Participants in this group will receive a daily dose of probiotics as an adjunct to standard Neratinib therapy. The probiotics will be administered orally as a granule formulation dissolved in water, for a total duration of 6 weeks (two treatment cycles). Loperamide will be administered prophylactically according to the FDA-recommended schedule to prevent Neratinib-associated diarrhea. The aim is to assess the efficacy of probiotics in reducing Neratinib-induced diarrhea and improving quality of life.

Probiotics + Neratinib + Loperamide

Placebo DIETARY_SUPPLEMENT

Participants in this group will receive a daily dose of a placebo that is identical in appearance, taste, and administration method to the probiotic granules, in addition to standard Neratinib therapy. The placebo will be administered orally as a granule formulation dissolved in water, for a total duration of 6 weeks. Loperamide will also be administered prophylactically to all participants in accordance with FDA recommendations. This group will serve as a control to evaluate the true effect of probiotics on Neratinib-induced diarrhea.

Placebo + Neratinib + Loperamide

Loperamide DRUG

All participants will receive prophylactic loperamide to reduce the risk of Neratinib-induced diarrhea. Loperamide will be administered according to the FDA-recommended schedule: 4 mg TID for the first 14 days of treatment, then 4 mg BID from Day 15 to Day 42. This intervention is implemented as a standard supportive therapy and not as a randomized variable.

Placebo + Neratinib + Loperamide; Probiotics + Neratinib + Loperamide

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants must meet all of the following criteria:
• Female patients aged ≥18 years, diagnosed with HER2-positive breast cancer.
• Scheduled to receive Neratinib therapy (monotherapy or in combination), based on clinical guidelines.
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2, with an expected survival of at least 3 months.
• Left ventricular ejection fraction (LVEF) ≥ 50%.
• Resolution of any prior treatment-related toxicity to Grade ≤1 (per CTCAE v5.0), with AST and ALT ≤ 2.5 × the upper limit of normal (ULN), and total bilirubin ≤ 1.5 × ULN.
• Adequate bone marrow function, defined as:
• White blood cell count ≥ 3.0 × 10⁹/L Neutrophil count ≥ 1.5 × 10⁹/L Platelet count ≥ 100 × 10⁹/L Hemoglobin ≥ 90 g/L Serum creatinine ≤ 1.5 × ULN
• No persistent gastrointestinal symptoms, such as hematochezia, chronic constipation, or abdominal pain.
• No evidence of structural gastrointestinal abnormalities confirmed by gastroscopy or other relevant examinations.

You may not qualify if:

• Participants will be excluded if they meet any of the following criteria:
• Conditions that significantly impair swallowing, digestion, or gastrointestinal drug absorption.
• History of chronic gastrointestinal diseases, including but not limited to inflammatory bowel disease (IBD), gastrointestinal tumors, or malabsorption syndromes.
• Severe cardiovascular diseases that may interfere with study treatment, including but not limited to:
• Life-threatening arrhythmias Advanced atrioventricular block Unstable angina Clinically significant pericardial disease Myocardial fibrosis Uncontrolled hypertension
• Known hypersensitivity to any component of Neratinib, probiotics, placebo, or loperamide.
• Prior participation in any clinical trial involving investigational drugs within 4 weeks prior to enrollment, or chronic use of medications that may induce constipation within 6 months.
• Pregnant or lactating women, or those unwilling to use effective contraception during the study period.
• Any medical, psychiatric, or social condition that, in the investigator's judgment, could compromise the safety of the participant, interfere with study participation, or confound the study results.

Sponsors & Collaborators

• Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University: lead
• Jiangnan University: collaborator

Study Sites (1)

Breast Tumor Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen University

Guangzhou, Guangdong, China

RECRUITING

MeSH Terms

Conditions

Diarrhea; Breast Neoplasms

Interventions

Probiotics; Loperamide

Condition Hierarchy (Ancestors)

Signs and Symptoms, Digestive; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Dietary Supplements; Food; Diet, Food, and Nutrition; Physiological Phenomena; Food and Beverages; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Central Study Contacts

Jianli Zhao

CONTACT

+86 15920589334; zhaojianli1988@126.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 11, 2025
• First Posted: March 24, 2025
• Study Start: August 7, 2025
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): December 1, 2027
• Last Updated: September 8, 2025

Record last verified: 2025-03

Locations

CN (1)