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

Breast Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05030519
• Other study ID #: intestinal flora study
• Status: Recruiting
• Start date: January 18, 2021
• Est. completion date: December 30, 2022

Study information

• Verified date: February 2022
• Source: Zhejiang Cancer Hospital
• Contact: Wenming Cao, Ph.D.
• Phone: +86 057188122222
• Email: caowm[@]zjcc.org.cn
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 50
• Est. completion date: December 30, 2022
• Est. primary completion date: June 30, 2022
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

1. Female breast cancer patients aged 18-75 years.

2. ECOG performance status of 0 to 1;

3. Known hormone receptor status;

4. HER2 positive breast cancer and previously reveived =2 anti-HER2 therapy;

5. Breast cancer patients are about to receive pyrotinib monotherapy or combined with Trastuzumab/Inetetamab and chemotherapy;

6. 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;

7. Signed the informed consent form prior to patient entry, and have good compliance and are willing to cooperate with follow-up.

Exclusion Criteria:

1. patients with Severe heart disease or discomfor;

2. Previous or ongoing use of HER2-targeted tyrosine kinase inhibitors ;

3. Inability to swallow, intestinal obstruction, or other factors that affect the taking and absorption of the drug;

4. Allergy to pyrotinib; history of immunodeficiency, including HIV positive, active HBV/HCV, other acquired or congenital immunodeficiency disease and organ transplantation history;

5. 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;

6. 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.

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms
• Diarrhea

Intervention

Drug:
• Pyrotinib
Pyrotinib 400 mg once daily(monotherapy or combined Trastuzumab/Inetetamab and chemotherapy)

Locations

Country	Name	City	State
China	China	Zhejiang	Hangzhou

Sponsors (1)

Lead Sponsor	Collaborator
Zhejiang Cancer Hospital

Country where clinical trial is conducted

China, 

References & Publications (10)

Fernández MF, Reina-Pérez I, Astorga JM, Rodríguez-Carrillo A, Plaza-Díaz J, Fontana L. Breast Cancer and Its Relationship with the Microbiota. Int J Environ Res Public Health. 2018 Aug 14;15(8). pii: E1747. doi: 10.3390/ijerph15081747. Review. — View Citation

Freudenberg JA, Wang Q, Katsumata M, Drebin J, Nagatomo I, Greene MI. The role of HER2 in early breast cancer metastasis and the origins of resistance to HER2-targeted therapies. Exp Mol Pathol. 2009 Aug;87(1):1-11. doi: 10.1016/j.yexmp.2009.05.001. Epub — View Citation

Gaudet MM, Gierach GL, Carter BD, Luo J, Milne RL, Weiderpass E, Giles GG, Tamimi RM, Eliassen AH, Rosner B, Wolk A, Adami HO, Margolis KL, Gapstur SM, Garcia-Closas M, Brinton LA. Pooled Analysis of Nine Cohorts Reveals Breast Cancer Risk Factors by Tumo — View Citation

Goedert JJ, Jones G, Hua X, Xu X, Yu G, Flores R, Falk RT, Gail MH, Shi J, Ravel J, Feigelson HS. Investigation of the association between the fecal microbiota and breast cancer in postmenopausal women: a population-based case-control pilot study. J Natl — View Citation

Ley RE, Peterson DA, Gordon JI. Ecological and evolutionary forces shaping microbial diversity in the human intestine. Cell. 2006 Feb 24;124(4):837-48. Review. — View Citation

Ma H, Bernstein L, Pike MC, Ursin G. Reproductive factors and breast cancer risk according to joint estrogen and progesterone receptor status: a meta-analysis of epidemiological studies. Breast Cancer Res. 2006;8(4):R43. — View Citation

Parida S, Sharma D. The power of small changes: Comprehensive analyses of microbial dysbiosis in breast cancer. Biochim Biophys Acta Rev Cancer. 2019 Apr;1871(2):392-405. doi: 10.1016/j.bbcan.2019.04.001. Epub 2019 Apr 11. Review. — View Citation

Ross JS. Breast cancer biomarkers and HER2 testing after 10 years of anti-HER2 therapy. Drug News Perspect. 2009 Mar;22(2):93-106. doi: 10.1358/dnp.2009.22.2.1334452. Review. — View Citation

Wu AH, Tseng C, Vigen C, Yu Y, Cozen W, Garcia AA, Spicer D. Gut microbiome associations with breast cancer risk factors and tumor characteristics: a pilot study. Breast Cancer Res Treat. 2020 Jul;182(2):451-463. doi: 10.1007/s10549-020-05702-6. Epub 2020 — View Citation

Yang J, Tan Q, Fu Q, Zhou Y, Hu Y, Tang S, Zhou Y, Zhang J, Qiu J, Lv Q. Gastrointestinal microbiome and breast cancer: correlations, mechanisms and potential clinical implications. Breast Cancer. 2017 Mar;24(2):220-228. doi: 10.1007/s12282-016-0734-z. Ep — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	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
Secondary	Overall Survival(OS)	Time interval from randomization to death for any reason	January 2021- December 2022
Secondary	Progression Free Survival (PFS)	Time interval from randomization to first disease progression or death for any reason	January 2021- December 2022
Secondary	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