Mechanism Exploration of Anti-HER-2 Small-molecule Tyrosine Kinase Inhibitor-related Diarrhea and Establishment of Prevention and Treatment Model(Measure)

A Prospective Phase II Study About Mechanism Exploration of Anti-HER-2 Small-molecule Tyrosine Kinase Inhibitor-related Diarrhea and Establishment of Prevention and Treatment Model in HER2+ Breast Cancer

Small-molecule tyrosine kinase inhibitors (TKI) that target HER2 are routinely used to treat patients with HER2 (+) breast cancer. The main adverse reactions included diarrhea, nausea, and rash, among which diarrhea had the highest incidence. It can reduce the quality of life and medication compliance of patients, and further affect the efficacy of TKI anti-tumor therapy. Therefore, the investigators conducted this study to establish a risk assessment model before TKI treatment, in order to screen out the high-risk population and influencing factors of TKI-associated diarrhea, and planned to carry out corresponding animal experiments to verify the relationship between various mechanisms and the main mechanism in TKI-associated diarrhea and to explore the corresponding treatment methods.

Study Overview

• Status: Recruiting
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: Take probiotics

• Study Type: Interventional
• Enrollment (Anticipated): 100
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Xu Fei, MD; Phone Number: +86-13711277870; Email: xufei@sysucc.org.cn
• Study Contact Backup: Name: Jiang Kuikui, MD; Phone Number: +86-15210589011; Email: jiangkk@sysucc.org.cn

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510000
      • Recruiting
      • Sun Yat-sen University Cancer Center
      • Contact: Fei Xu, MD; Phone Number: +86-13711277870; Email: xufei@sysucc.org.cn
      • Principal Investigator: Fei Xu, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Plan to take pyrrolidine or naratinib for ≥ 28 days;
• HER2 positive female patients with breast cancer aged ≥ 18 years and ≤ 65 years;
• Patients with the following treatment schemes: 1. Pirotinib/naratinib monotherapy 2. Pirotinib/naratinib combined endocrine therapy; 4. The ECOG score is 0-1;
• Life expectancy ≥ 6 months;
• Patients who followed diet intervention after enrollment;
• Volunteer to join the study, sign the informed consent form, have good compliance and are willing to cooperate with follow-up.

Exclusion Criteria:

• People who may be allergic to pyrrolidine, naratinib or excipients;
• There are many factors that affect the absorption of oral drugs, such as inability to swallow, nausea and vomiting;
• Patients with biliary obstruction;
• Participate in other clinical trials related to diarrhea;
• Pregnant and lactating women, women with fertility and positive baseline pregnancy test, or women of childbearing age who are unwilling to take effective contraceptive measures during the whole trial period;
• According to the judgment of the investigator, there are concomitant diseases (including but not limited to severe hypertension and severe diabetes beyond drug control) that seriously endanger the patient's safety or affect the patient's completion of the study;
• Have taken other drugs that may cause diarrhea adverse reactions within 3 weeks before enrollment;
• There are drugs with high probability of causing diarrhea adverse reactions in patients' combined medication;
• Any other situation in which the researcher believes that the patient is not suitable to participate in this study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Diarrhea group; Patients with diarrhea after taking pyrrolidine/naratinib，implement intervention (Yihuo 0.2g po bid+ Gold bifidum 2g po tid)	Drug: Take probiotics; Take medication for 21 days (Yihuo 0.2g bid+ Jin Bifid2g tid)
No Intervention: No diarrhea group; Patients without diarrhea after taking pyrrolidine/naratinib

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Diarrhea grading	Score according to the diarrhea grading：grading score： 0（None）；1（Increased bowel movements < 4 times per day compared to before treatment）； 2（Increased bowel movements 4 to 6 times/day or night compared to before treatment）；3（ Increased number of stools ≥ 7 times/day compared with before treatment, fecal incontinence, severe abdominal pain or fecal incontinence, affecting daily activities and requiring hospitalization）； 4（life-threatening (e.g. circulatory failure））；5（Death）.	28 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time of the first occurrence of diarrhea	The median time of the first occurrence of diarrhea	28 days
Duration of diarrhea	The median duration of diarrhea	28 days
Time of the first occurrence of grade 3 diarrhea	The median time of the first occurrence of grade 3 diarrhea	28 days
Duration of grade 3 diarrhea	The median duration of grade 3 diarrhea	28 days
Adverse events	Occurrence of other adverse events	28 days

Collaborators and Investigators

• Sponsor: Sun Yat-sen University

Study record dates

Study Major Dates

• Study Start (Anticipated): April 12, 2023
• Primary Completion (Anticipated): August 1, 2023
• Study Completion (Anticipated): August 1, 2024

Study Registration Dates

• First Submitted: March 6, 2023
• First Submitted That Met QC Criteria: March 6, 2023
• First Posted (Actual): March 17, 2023

Study Record Updates

• Last Update Posted (Estimate): April 13, 2023
• Last Update Submitted That Met QC Criteria: April 11, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Signs and Symptoms, Digestive; Breast Diseases; Breast Neoplasms; Diarrhea
• Other Study ID Numbers: SYSU-2022-01

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No