A Study of Diarrhea and Intestinal Flora Changes Caused by Pyrotinib in Breast Cancer

Study Overview
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Brief Summary
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By measuring the intestinal flora abundance and bacterial count of patients in the early stage of using pyrotinib to clarify the relationship between diarrhea caused by pyrotinib and changes in intestinal flora in breast cancer patients, the correlation between the change of intestinal flora and the relief of diarrhea are also explored after two-cycle treatment.

Detailed Description
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In recent years, small-molecule tyrosine kinase inhibitors (TKI) have achieved good results in anti-HER2 therapy and have been widely used in clinical practice, such as Breast cancer. However, such drugs can easily cause diarrhea and disorders of intestinal flora , may affect the efficacy of the drug and lead to the occurrence of other diseases.This study is to clarify the connection between the diarrhea caused by pyrotinib and the change of intestinal flora, pave the way for studying on whether the flora affects the efficacy of the drug and whether the flora should be supplemented appropriately in the future.

Official Title
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A Study of Diarrhea and Intestinal Flora Changes Caused by Pyrotinib in Breast Cancer

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: Pyrotinib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Female breast cancer patients aged 18-75 years. ECOG performance status of 0 to 1; Known hormone receptor status; HER2 positive breast cancer and previously reveived ≤2 anti-HER2 therapy; Breast cancer patients are about to receive pyrotinib monotherapy or combined with Trastuzumab/Inetetamab and chemotherapy； Patients with adequate organ function before enrollment (no blood transfusion, no white blood cell or platelet-elevating drugs used within 2 weeks before screening): 1) Blood routine:ANC≥1.5×10^9/L; PLT≥90×10^9/L; Hb≥90 g/L；2)Blood biochemistry: TBIL≤1.5×ULN;ALT and AST ≤1.5×ULN; alkaline phosphatase ≤ 2.5×ULN; BUN and Cr≤1.5×ULN；3) Cardiac color Doppler ultrasound:LVEF≥55%；4) 12-lead ECG: QTcF < 470 msec; Signed the informed consent form prior to patient entry, and have good compliance and are willing to cooperate with follow-up. Exclusion Criteria: patients with Severe heart disease or discomfor; Previous or ongoing use of HER2-targeted tyrosine kinase inhibitors ; Inability to swallow, intestinal obstruction, or other factors that affect the taking and absorption of the drug; Allergy to pyrotinib; history of immunodeficiency, including HIV positive, active HBV/HCV, other acquired or congenital immunodeficiency disease and organ transplantation history; Patients during pregnancy or lactation, patients with childbearing potential tested positive in baseline pregnancy test, or patients unwilling to take effective contraceptive measures throughout the trial and 7 months after the last study medication; patients with intestinal disease, serious concomitant diseases, or other comorbid diseases that will interfere with the planned treatment, or patients not eligible for this study judged by the investigator.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: Pyrotinib|Pyrotinib 400 mg once daily(monotherapy or combined Trastuzumab/Inetetamab and chemotherapy)|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The quantity of intestinal flora from breast cancer patients' fecal microflora at different follow-up nodes | Fecal samples were collected from patients at each follow-up node to detect the number of bacterial species in the intestinal flora | January 2021- December 2022 | 
| The abundance of intestinal flora from breast cancer patients' fecal microflora at different follow-up nodes | Fecal samples were collected at each follow-up node to detect the richness of different bacterial species in intestinal flora | January 2021- December 2022 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease Control Rate（DCR） | DCR=CR+PR+SD Complete Remission(CR): All target lesions disappeared, no new lesions appeared, and tumor markers were normal, for at least 4 weeks; Partial Remission(PR): The sum of the maximum diameter of the target lesion is reduced by ≥30% and maintained for at least 4 weeks; Stable Disease(SD): The maximum diameter and reduction of the target lesion did not reach the PR, or the enlargement did not reach the PD; | January 2021- December 2022 | 
| Overall Survival（OS） | Time interval from randomization to death for any reason | January 2021- December 2022 | 
| Progression Free Survival (PFS) | Time interval from randomization to first disease progression or death for any reason | January 2021- December 2022 | 
| Objective Response Rate (ORR) | ORR=CR+PR Complete Remission(CR): All target lesions disappeared, no new lesions appeared, and tumor markers were normal, for at least 4 weeks; Partial Remission(PR): The sum of the maximum diameter of the target lesion is reduced by ≥30% and maintained for at least 4 weeks; | January 2021- December 2022 |