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

Not Applicable

Recruiting

• Conditions: HER2-positive Breast Cancer; Diarrhea Caused by Drug; Neratinib
• Interventions: Dietary Supplement: Probiotics; Dietary Supplement: Placebo; Drug: Loperamide

• Registration Number: NCT06892093
• Lead Sponsor: Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University

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.

Detailed Description

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.

Study Timeline

• Status Verified: 2025-03
• Study First Submitted: 2025-03-11
• Study First Submitted QC: 2025-03-18
• Study First Posted: 2025-03-24
• Study Start: 2025-08-07
• Last Update Submitted: 2025-08-29
• Last Update Posted: 2025-09-08
• Primary Completion: 2027-06
• Study Completion: 2027-12-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: Female
• Target Recruitment: 308

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Probiotics + Neratinib + Loperamide	Probiotics	-
Probiotics + Neratinib + Loperamide	Loperamide	-
Placebo + Neratinib + Loperamide	Placebo	-
Placebo + Neratinib + Loperamide	Loperamide	-

Primary Outcome Measures

Name	Time	Method
Incidence of Grade ≥3 Diarrhea	Up to 6 weeks	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.

Secondary Outcome Measures

Name	Time	Method
Incidence of Any Grade Diarrhea	Up to 6 weeks	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.
Duration of First Episode of Grade 3 Diarrhea	Up to 6 weeks	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).
Proportion of Participants Hospitalized Due to Diarrhea	Up to 6 weeks	The proportion of participants who require hospitalization due to diarrhea-related complications during the treatment period.
Loperamide Usage Patterns	Up to 6 weeks	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.
Change from Baseline in Overall Quality of Life Assessed by EORTC QLQ-C30	Baseline, Weeks 2, 4, and 6 (End of Study)	Changes in quality of life assessed using the EORTC QLQ-C30 questionnaire. The tool evaluates overall health status and functioning, including physical, role, emotional, cognitive, and social domains. Higher scores in functional and global health scales indicate better quality of life, while higher scores in symptom scales indicate greater symptom burden.
Change from Baseline in Diarrhea-Related Quality of Life Assessed by FACT-D	Baseline, Weeks 2, 4, and 6 (End of Study)	Changes in diarrhea-related quality of life assessed using the FACT-D subscale of the Functional Assessment of Cancer Therapy system. This tool specifically evaluates the severity and impact of diarrhea symptoms on patients' daily life and well-being. Higher scores indicate fewer symptoms and better diarrhea-related quality of life.
Incidence of Treatment-Related Adverse Events (AEs)	Up to 6 weeks	The incidence of treatment-related adverse events (AEs) in participants receiving probiotics plus Neratinib versus the control group. AEs, including nausea, allergic reactions, and other related symptoms, will be assessed according to the Common Terminology Criteria for Adverse Events (CTCAE), version 5.0.
Incidence of Serious Adverse Events (SAEs)	Up to 6 weeks	The incidence of serious adverse events (SAEs) associated with probiotics or Neratinib treatment. SAEs, including severe allergic reactions, life-threatening complications, or hospitalizations, will be recorded and summarized to assess potential safety concerns.
Rate of Treatment Discontinuation Due to Adverse Events	Up to 6 weeks	The proportion of participants who discontinue Neratinib treatment due to adverse events. The outcome will compare discontinuation rates between the probiotic and placebo groups to evaluate tolerability.

Trial Locations

Locations (1)

Breast Tumor Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen University; 🇨🇳 Guangzhou, Guangdong, China