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

ConditionsHER2-positive Breast Cancer Diarrhea Caused by Drug Neratinib

Trial statusRecruiting

Trial phaseNot applicable

Trial typeInterventional

Biological sexFemale

Age18+

SponsorSun Yat-Sen Memorial Hospital of Sun Yat-Sen University

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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%.

Disqualifiers

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.

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.

Trial design

Design model

Parallel

Treatments tested in this trial

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.
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.
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.

Treatment groups

308 Participants

are divided into 2 treatment groups

Group A: Probiotics + Neratinib + LoperamideExperimental treatment 2 interventions

Group B: Placebo + Neratinib + LoperamidePlacebo comparator 2 interventions

Trial outcomes

Primary outcomes

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.

Time frame

Up to 6 weeks

Secondary outcomes

Incidence of Any Grade Diarrhea

The incidence of diarrhea of any grade during the 6-week treatment period, assessed according to the Common Terminology Criteria for Adverse Events (CTCAE), version 5.0.

Time frame

Up to 6 weeks

Duration of First Episode of Grade 3 Diarrhea

The duration (in days) of the first episode of grade 3 diarrhea experienced by participants during the 6-week treatment period, assessed using the Common Terminology Criteria for Adverse Events (CTCAE), version 5.0. Duration is defined from onset to recovery (downgrade to grade ≤2).

Time frame

Up to 6 weeks

Proportion of Participants Hospitalized Due to Diarrhea

The proportion of participants who require hospitalization due to diarrhea-related complications during the treatment period.

Time frame

Up to 6 weeks

Loperamide Usage Patterns

Frequency, total dosage, and compliance of loperamide use during the treatment period, including any dose modifications or discontinuation. Data will be collected through medication records and patient diaries.

Time frame

Up to 6 weeks

Other outcomes

Gut Microbiota Composition Changes

Analysis of stool samples collected at baseline, week 3, and week 6 to assess changes in gut microbiota composition in response to probiotic intervention. The goal is to determine whether probiotics modulate the intestinal microbiota and exert a protective effect against Neratinib-associated diarrhea.

Time frame

Baseline, Week 3, and Week 6

Correlation Analysis of Gut Microbiota-Metabolite-Immune Axis

Integrated analysis of gut microbiota composition, blood and gut microbial metabolites, and immune response markers. This study aims to explore potential mechanistic links between gut microbiota, metabolite changes, and immune function.

Time frame

Baseline, Week 3, and Week 6

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University

Lead sponsor

Jiangnan University

Collaborator

Source ClinicalTrials.gov

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