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

NCT ID: NCT06892093

Last Updated: 2025-09-08

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

NA

Total Enrollment

308 participants

Study Classification

INTERVENTIONAL

Study Start Date

2025-08-07

Study Completion Date

2027-12-31

Brief Summary

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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.

Detailed Description

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Breast cancer patients treated with the tyrosine kinase inhibitor (TKI) Neratinib often experience severe diarrhea, leading to treatment interruptions, dose reductions, or discontinuation. Emerging evidence highlights the role of gut microbiota in drug metabolism and gastrointestinal toxicity. Probiotics have been proposed as a potential intervention to modulate gut microbiota and mitigate diarrhea; however, their efficacy in preventing Neratinib-induced diarrhea remains inconclusive.

This randomized, double-blind, placebo-controlled clinical trial aims to evaluate the efficacy and safety of probiotics in preventing diarrhea in HER2-positive breast cancer patients receiving Neratinib. The study will also explore the impact of probiotics on gut microbiota composition and potential microbiome-mediated mechanisms that may enhance treatment adherence and therapeutic outcomes.

Participants will be randomly assigned in a 1:1 ratio to either a probiotics group or a placebo group. Both groups will receive prophylactic loperamide in accordance with the dosing schedule recommended by the U.S. Food and Drug Administration (FDA) for the prevention of Neratinib-associated diarrhea, ensuring consistency with the approved prescribing information.

Participants will receive treatment for a total of six weeks, corresponding to two treatment cycles.

Metagenomic sequencing and targeted metabolomics will be performed on stool samples to investigate gut microbial composition and metabolic changes. Additional analyses will assess the association between gut-derived metabolites and immune cell activation, aiming to elucidate potential interactions among gut microbiota, metabolites, and immune responses.

Sun Yat-sen Memorial Hospital will serve as the coordinating center for this planned multicenter trial. Currently, it is the only active site, and additional participating centers will be added progressively as they are initiated.

Conditions

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HER2-positive Breast Cancer Diarrhea Caused by Drug Neratinib

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Probiotics + Neratinib + Loperamide

Group Type EXPERIMENTAL

Probiotics

Intervention Type 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.

Loperamide

Intervention Type 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

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type 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

Intervention Type 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.

Interventions

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Probiotics

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.

Intervention Type DIETARY_SUPPLEMENT

Placebo

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.

Intervention Type DIETARY_SUPPLEMENT

Loperamide

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.

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

Participants must meet all of the following criteria:

1. Female patients aged ≥18 years, diagnosed with HER2-positive breast cancer.
2. Scheduled to receive Neratinib therapy (monotherapy or in combination), based on clinical guidelines.
3. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2, with an expected survival of at least 3 months.
4. Left ventricular ejection fraction (LVEF) ≥ 50%.
5. 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.
6. 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
7. No persistent gastrointestinal symptoms, such as hematochezia, chronic constipation, or abdominal pain.
8. No evidence of structural gastrointestinal abnormalities confirmed by gastroscopy or other relevant examinations.

Exclusion Criteria

Participants will be excluded if they meet any of the following criteria:

1. Conditions that significantly impair swallowing, digestion, or gastrointestinal drug absorption.
2. History of chronic gastrointestinal diseases, including but not limited to inflammatory bowel disease (IBD), gastrointestinal tumors, or malabsorption syndromes.
3. 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
4. Known hypersensitivity to any component of Neratinib, probiotics, placebo, or loperamide.
5. 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.
6. Pregnant or lactating women, or those unwilling to use effective contraception during the study period.
7. 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.
Minimum Eligible Age

18 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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Jiangnan University

OTHER

Sponsor Role collaborator

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

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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

Guangzhou, Guangdong, China

Site Status RECRUITING

Countries

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China

Central Contacts

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Jianli Zhao

Role: CONTACT

+86 15920589334

Facility Contacts

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Jianli Zhao

Role: primary

+86 15920589334

Other Identifiers

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SYSKY-2025-105-02

Identifier Type: -

Identifier Source: org_study_id

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