Probiotics to prevent neratinib-related diarrhea in HER2-positive breast cancer patients

Efficacy and Safety of Probiotics Versus Standard Care in Preventing Diarrhea Induced by Neratinib in Breast Cancer Patients: A Prospective Randomized Controlled Clinical Trial

This trial will test whether taking probiotics alongside standard preventive loperamide can reduce diarrhea in people with HER2-positive breast cancer who are starting neratinib compared with placebo.

Quick facts

• Phase: NA
• Study type: Interventional
• Enrollment: 308 (estimated)
• Ages: 18 Years and up
• Sex: Female
• Sponsor: Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University (other)
• Drugs / interventions: Neratinib
• Locations: 1 site (Guangzhou, Guangdong)
• Trial ID: NCT06892093 on ClinicalTrials.gov

What this trial studies

This is a randomized, double-blind, placebo-controlled trial enrolling HER2-positive breast cancer patients who are starting neratinib. Participants are assigned 1:1 to receive either probiotics or placebo while all participants receive prophylactic loperamide per FDA dosing for six weeks (two treatment cycles). The primary outcome is the incidence and severity of neratinib-associated diarrhea, and secondary analyses include stool metagenomic sequencing and targeted metabolomics to characterize gut microbiota changes. Safety, tolerability, and treatment adherence will also be recorded.

Who should consider this trial

Good fit: Women aged 18 or older with HER2-positive breast cancer who are scheduled to start neratinib, have ECOG ≤2, adequate cardiac, liver, renal, and bone marrow function, and no active structural gastrointestinal disease are ideal candidates.

Not a fit: Patients with ongoing GI structural abnormalities, active significant gastrointestinal symptoms, inadequate organ function, or those not receiving neratinib are unlikely to benefit from this intervention.

Why it matters

Potential benefit: If effective, probiotics could reduce the frequency and severity of neratinib-associated diarrhea, helping patients stay on full treatment and improving quality of life.

How similar studies have performed: Some smaller studies and clinical experience suggest probiotics can help with certain chemotherapy- or antibiotic-related diarrheas, but benefit specifically for neratinib-induced diarrhea remains unproven.

Eligibility criteria

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.

Where this trial is running

Guangzhou, Guangdong

• Breast Tumor Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen University — Guangzhou, Guangdong, China (RECRUITING)

Study contacts

• Study coordinator: Jianli Zhao

Conditions: HER2-positive Breast Cancer, Diarrhea Caused by Drug, Neratinib, Probiotics, Diarrhea, Breast Cancer