Gut Microbiota and Diarrhea in Breast Cancer Patients Receiving Pyrotinib

NCT07264985 | Not Yet Recruiting

• 1 other identifier: LLHBCH2025YN-087
• Study Type: observational
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

Background: Pyrotinib is an effective targeted drug for HER2-positive breast cancer, but it very frequently causes diarrhea, which can be severe enough to disrupt treatment and reduce patients' quality of life. The reason why some patients develop diarrhea while others do not is not well understood. Recent research suggests that the community of bacteria in the gut (gut microbiota) may play a key role in this side effect. What is the purpose of this study? This is an observational study (Phase 1) that aims to understand the relationship between pyrotinib treatment, changes in gut bacteria, and the occurrence of diarrhea. The main goal is to compare the gut bacteria of patients who develop diarrhea while taking pyrotinib with those who do not. Researchers hope to identify specific bacteria that might protect against diarrhea, which could lead to new ways to prevent or treat this side effect in the future. What will happen in the study? Patients with HER2-positive breast cancer who are being treated with pyrotinib will be invited to participate. They will be divided into two groups: those who experience diarrhea and those who do not. Participants will provide stool samples at specific time points (e.g., 2 and 4 weeks after starting pyrotinib). They will also allow researchers to collect information from their medical records about their clinical condition and diarrhea symptoms. No experimental intervention will be administered in this phase of the study; all patients will receive standard medical care. Potential Benefits: Participants will not receive any direct benefit from this observational phase of the study. However, the information gathered may help scientists better understand pyrotinib-induced diarrhea and develop future strategies to help other breast cancer patients manage this side effect more effectively.

Conditions

Breast Cancer; Drug-Related Side Effects; Diarrhea

Keywords

Pyrotinib; Diarrhea; Gut Microbiota; HER2-Positive Breast Cancer; Microbiome; Drug Side Effect; Metagenomics; Observational Study

Outcome Measures

Primary Outcomes (2)

• Difference in gut microbiota β-diversity between the Diarrhea group and the Non-diarrhea group.

  Beta diversity (e.g., using UniFrac distance) of the gut microbiota will be compared between the two groups based on metagenomic sequencing data. A statistically significant difference (P \< 0.05) is expected.

  Through study completion, an average of 6 months.

• Identification of specific bacterial species enriched in the Non-diarrhea group.

  Metagenomic sequencing data will be analyzed to identify bacterial species that are significantly more abundant in the Non-diarrhea group compared to the Diarrhea group, using statistical methods such as LEfSe (Linear Discriminant Analysis Effect Size) with a threshold of LDA Score \> 2 and P \< 0.05.

  Through study completion, an average of 6 months.

Secondary Outcomes (4)

• Difference in gut microbiota α-diversity between groups.

  Through study completion, an average of 6 months.

• Differences in metagenomic functional pathways between groups.

  Through study completion, an average of 6 months.

• Differences in serum inflammatory cytokine levels between groups.

  Through study completion, an average of 6 months.

• Differences in serum metabolomic profiles between groups.

  Through study completion, an average of 6 months.

Other Outcomes (1)

• Predictive potential of baseline gut microbiota for pyrotinib-induced diarrhea risk.

  Through study completion, an average of 6 months.

Study Arms (2)

Diarrhea Group

This cohort consists of HER2-positive breast cancer patients receiving pyrotinib treatment who develop diarrhea (graded as ≥ Grade 1 according to CTCAE v5.0) during the observation period. Participants in this group will provide stool samples and clinical data for comparison with the non-diarrhea group. No study intervention is administered; all patients receive standard medical care.

Non-Diarrhea Group

This cohort consists of HER2-positive breast cancer patients receiving pyrotinib treatment who do not develop diarrhea (Grade 0 according to CTCAE v5.0) during the observation period. Participants in this group will provide stool samples and clinical data, serving as a control for comparison with the diarrhea group. No study intervention is administered; all patients receive standard medical care.

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

The study population consists of adult patients (aged 18-75) diagnosed with HER2-positive breast cancer who are currently undergoing treatment with pyrotinib (either as monotherapy or in combination). This is a prospective observational cohort study where participants are not assigned to an intervention but are instead grouped based on the natural outcome of whether they develop drug-induced diarrhea during the observation period. This creates two primary cohorts for comparison: the 'Diarrhea Group' and the 'Non-Diarrhea Group'. All participants will continue their standard pyrotinib treatment and clinical care throughout the study.

You may qualify if:

• Patients aged 18-75 years, regardless of gender.
• Diagnosed with HER2-positive breast cancer and currently receiving pyrotinib treatment (either as monotherapy or in combination with endocrine therapy), with a treatment duration of ≥ 2 weeks.
• Voluntarily agree to participate in this study and provide written informed consent.

You may not qualify if:

• History of significant gastrointestinal diseases (e.g., inflammatory bowel disease, Crohn's disease, ulcerative colitis, intestinal obstruction) or previous major gastrointestinal surgery.
• Recent use (within 1 month) of antibiotics, probiotics, or traditional Chinese medicine intended to alter intestinal function.
• Pregnant or lactating women.

Sponsors & Collaborators

• Hubei Cancer Hospital: lead

Study Sites (1)

Hubei Cancer Hospital

Wuhan, Hubei, 430079, China

Location

Biospecimen

Retention: SAMPLES WITH DNA

Feces: Fresh stool samples (approximately 5g per collection) will be collected from participants at specified time points during pyrotinib treatment (e.g., at 2 weeks and 4 weeks). These samples will be immediately stored at -80°C. Genomic DNA will be extracted from these samples for metagenomic sequencing to analyze the composition and function of the gut microbiota. Blood: Peripheral blood samples (5mL in EDTA tubes for plasma and 5mL in serum separator tubes) will be collected during patient follow-up visits. After processing (centrifugation and aliquoting), the resulting plasma and serum samples will be stored at -80°C. These samples are intended for subsequent analyses, such as measuring systemic inflammatory cytokine levels (e.g., by ELISA) and potentially for metabolomic profiling.

MeSH Terms

Conditions

Breast Neoplasms; Diarrhea; Drug-Related Side Effects and Adverse Reactions

Condition Hierarchy (Ancestors)

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

Central Study Contacts

Xinhong Wu Wu, Principal Investigator

CONTACT

18602726300; wuxinhong_9@sina.com

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: vice-president

Study Record Dates

• First Submitted: November 24, 2025
• First Posted: December 4, 2025
• Study Start: December 1, 2025
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): July 1, 2026
• Last Updated: December 4, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)