Comparative Efficacy of Xiaopi Granules and Decoction in Triple-negative Breast Cancer: a Randomized Controlled Trial

Triple Negative Breast Neoplasms Clinical Trial

Official title:

Comparative Efficacy of Xiaopi Granules and Decoction in Improving Pathological Complete Response of Neoadjuvant Chemotherapy of Triple-negative Breast Cancer: a Randomized, Double-blind, Controlled Trial

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06154109
• Other study ID #: GuangdongXPRCT
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: November 25, 2023
• Est. completion date: March 30, 2026

Study information

• Verified date: November 2023
• Source: Guangdong Provincial Hospital of Traditional Chinese Medicine
• Contact: Zhiyu Wang, PhD
• Phone: +8618819480766
• Email: wangzhiyu[@]gzucm.edu.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The goal of this clinical trial is to compare the efficacy of xiaopi granules and decoction in improving the pathological complete response (pCR) of neoadjuvant chemotherapy of triple-negative breast cancer. The main objective aims to answer whether Xiaopi granules combined with neoadjuvant Chemotherapy could improve the pCR rate of triple-negative breast cancer. The secondary outcome included genomics of plasma extracellular vesicles, plasma metabolites and metabolomics, urine metabolomics, fecal intestinal flora tests, pathological tissue genomics, functional assessment of cancer therapy breast (FACT-B), and adverse events.

Participants enrolled in this study will be randomized to xiaopi granules plus neoadjuvant chemotherapy, or xiaopi decoction plus neoadjuvant chemotherapy, or placebo plus neoadjuvant chemotherapy alone.

Researchers will compare the pathological complete response between xiaopi granules and decoction group, and to determine their effects in chemosensitizing triple-negative breast cancer.

Description:

Background: Triple-negative breast cancers (TNBCs) are characterized by poor prognosis, rapid progression to metastatic stage, and onset of resistance to chemotherapy. Neoadjuvant chemotherapy is commonly used to improve the surgical pathological complete response rate (pCR) in stage II-III triple-negative breast cancer. However, chemotherapy can lead to immune escape and drug resistance in breast cancer cells, while the toxic side effects significantly affect patients' quality of life. The combination of Chinese herbal medicine and chemotherapy can improve survival rates while alleviating chemotherapy-related adverse events. Xiaopi Granules were developed by Professor Lin Yi, a renowned Traditional Chinese Medicine doctor in the field of breast diseases. The investigators' preliminary research has confirmed that Xiaopi Granules can inhibit tumor progression by targeting TAMs/CXCL1 signaling to suppress chemotherapy-induced autophagy, as well as inhibit the formation of tumor stem cells and pre-metastatic niches. Chinese medicine granules not only have several advantages compared to decoction, such as reliable drug quality and convenient administration but also have the characteristics of individualized prescription. However, whether their efficacy is comparable to that of the decoction granules still requires exploration. The investigators aimed to compare the efficacy of xiaopi granules and decoction in improving the pathological complete response of neoadjuvant chemotherapy of triple-negative breast cancer.

Hypothesis: Xiaopi granules can improve the pathological complete response of neoadjuvant chemotherapy of triple-negative breast cancer.

Patients and methods: Ninety patients with TNBC will be enrolled in this study and randomized to xiaopi granules plus neoadjuvant chemotherapy, xiaopi decoction plus neoadjuvant chemotherapy, or placebo plus neoadjuvant chemotherapy. The primary aim is the rate of pathological complete response (pCR, defined as the absence of invasive cells in breast and lymph nodes). The secondary outcome included genomics of plasma extracellular vesicles, plasma metabolites and metabolomics, urine metabolomics, fecal intestinal flora tests, pathological tissue genomics, functional assessment of cancer Therapy-Breast(FACT-B), and safety( AE and SAE). The neoadjuvant chemotherapy is carried out based on the National Comprehensive Cancer Network (NCCN) guidelines. Different treatments and doses are set according to the standard recommendations outlined in the guidelines. In addition to receiving neoadjuvant chemotherapy, the participants will be subjected to Xiaopi granules or decoction orally at a dosage of 18g per bag, twice daily, for a total of 8 days per treatment course. The duration of the treatment course will align with that of the chemotherapy regimen. A placebo is a look-alike substance that contains no active drug.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 90
• Est. completion date: March 30, 2026
• Est. primary completion date: December 30, 2025
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

• Females aged =18 and =75 years

• Pathological diagnosis of triple-negative breast cancer with stage II-III

• Not having received any previous treatment for breast cancer

• Having at least one measurable tumor

• No distant metastases

• ECOG score 0-2

• Neoadjuvant chemotherapy or combination immunotherapy

• Agree to participate in this clinical study and sign the informed consent form

Exclusion Criteria:

• Pregnant and breastfeeding, with fertility requirements during the study period

• Combined other malignant tumors

• Combination of serious diseases of the heart, brain, liver, kidney, and hematopoietic system, liver function impairment, and diabetes mellitus

• Active hepatitis B virus or hepatitis C virus infection, or human immunodeficiency virus (HIV) infection

• Presence of factors affecting the administration and absorption of the drug

• Allergy to the drug components of this regimen

• A history of psychotropic substance abuse or drug use

• The patient has other life-threatening diseases

• Participating in other drug trials

Related Conditions & MeSH terms

• Breast Neoplasms
• Triple Negative Breast Neoplasms

Intervention

Drug:
• Xiaopi granules
Xiaopi granules (18 g/ bag), 18 g/ time, 2 times/day, 8 days/course.
• Xiaopi decoction
Xiaopi decoction (18 g/ bag), 18 g/ time, 2 times/day, 8 days/course.
• Placebo
The placebo does not contain any active pharmaceutical ingredients .

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Zhiyu Wang

References & Publications (9)

Foulkes WD, Smith IE, Reis-Filho JS. Triple-negative breast cancer. N Engl J Med. 2010 Nov 11;363(20):1938-48. doi: 10.1056/NEJMra1001389. — View Citation

Mehraj U, Dar AH, Wani NA, Mir MA. Tumor microenvironment promotes breast cancer chemoresistance. Cancer Chemother Pharmacol. 2021 Feb;87(2):147-158. doi: 10.1007/s00280-020-04222-w. Epub 2021 Jan 9. — View Citation

Nedeljkovic M, Damjanovic A. Mechanisms of Chemotherapy Resistance in Triple-Negative Breast Cancer-How We Can Rise to the Challenge. Cells. 2019 Aug 22;8(9):957. doi: 10.3390/cells8090957. — View Citation

Park YH, Lal S, Lee JE, Choi YL, Wen J, Ram S, Ding Y, Lee SH, Powell E, Lee SK, Yu JH, Ching KA, Nam JY, Kim SW, Nam SJ, Kim JY, Cho SY, Park S, Kim J, Hwang S, Kim YJ, Bonato V, Fernandez D, Deng S, Wang S, Shin H, Kang ES, Park WY, Rejto PA, Bienkowska J, Kan Z. Chemotherapy induces dynamic immune responses in breast cancers that impact treatment outcome. Nat Commun. 2020 Dec 2;11(1):6175. doi: 10.1038/s41467-020-19933-0. — View Citation

Shi G, Yu D, Wu J, Liu Y, Huang R, Zhang CS. A systematic review and meta-analysis of traditional Chinese medicine with chemotherapy in breast cancer. Gland Surg. 2021 May;10(5):1744-1755. doi: 10.21037/gs-21-284. — View Citation

Shree T, Olson OC, Elie BT, Kester JC, Garfall AL, Simpson K, Bell-McGuinn KM, Zabor EC, Brogi E, Joyce JA. Macrophages and cathepsin proteases blunt chemotherapeutic response in breast cancer. Genes Dev. 2011 Dec 1;25(23):2465-79. doi: 10.1101/gad.180331.111. — View Citation

Wang N, Yang B, Muhetaer G, Wang S, Zheng Y, Lu J, Li M, Zhang F, Situ H, Lin Y, Wang Z. XIAOPI formula promotes breast cancer chemosensitivity via inhibiting CXCL1/HMGB1-mediated autophagy. Biomed Pharmacother. 2019 Dec;120:109519. doi: 10.1016/j.biopha.2019.109519. Epub 2019 Oct 17. Erratum In: Biomed Pharmacother. 2022 May;149:112867. — View Citation

Wang S, Liu X, Huang R, Zheng Y, Wang N, Yang B, Situ H, Lin Y, Wang Z. XIAOPI Formula Inhibits Breast Cancer Stem Cells via Suppressing Tumor-Associated Macrophages/C-X-C Motif Chemokine Ligand 1 Pathway. Front Pharmacol. 2019 Nov 15;10:1371. doi: 10.3389/fphar.2019.01371. eCollection 2019. — View Citation

Zheng Y, Wang N, Wang S, Yang B, Situ H, Zhong L, Lin Y, Wang Z. XIAOPI formula inhibits the pre-metastatic niche formation in breast cancer via suppressing TAMs/CXCL1 signaling. Cell Commun Signal. 2020 Mar 26;18(1):48. doi: 10.1186/s12964-020-0520-6. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Pathological complete response	Defined as the absence of invasive cells in breast and lymph nodes.	Through study completion,an average of 6 moths
Secondary	Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1	The RECIST 1.1 version is used as the standard for evaluating the clinical efficacy of solid tumors.	Through study completion, an average of 6 moths
Secondary	Genomics of plasma extracellular vesicles	Extracellular vesicles were isolated from the plasma of breast cancer patients using a differential ultracentrifugation method. High-throughput whole transcriptome sequencing was conducted to identify differentially expressed genes in the isolated extracellular vesicles. The primary experimental procedures for transcriptome sequencing analysis include RNA quantification and qualification, library preparation for transcriptome sequencing, clustering and sequencing, and data analysis. . Analysis of whole transcriptome microarray data was performed using BioConductor software based on the statistical R programming language.	Through study completion, an average of 6 moths
Secondary	Plasma Genomic Tests	Utilize the Ultimate U3000 HPLC (Thermo Fisher Scientific) coupled to Q Exactive Plus mass spec- trometer (Thermo Fisher Scientific) to detect differences in metabolites within the blood of different medication intervention treatment groups before and after medication.All data were acquired and analyzed with the Xcalibur 4.0 software (Thermo Fisher Scientific).	Through study completion, an average of 6 moths
Secondary	Urine Metabolomics Tests	Utilize the Vanquish ultra-high-performance liquid chromatography-mass spectrometry system (Thermo Fisher Scientific) to detect variations in metabolites within the urine of different medication intervention treatment groups before and after medication.All data were acquired and analyzed with the Xcalibur 4.0 software (Thermo Fisher Scientific).	Through study completion, an average of 6 moths
Secondary	Fecal Intestinal Flora Tests	Laboratory testing for differences in faecal intestinal flora testing before and after the patient's medication.	Through study completion, an average of 6 moths
Secondary	Pathological Tissue Genomics Tests	Using whole exome sequencing (WES) to perform high-throughput sequencing of the exonic regions in pathological tissues, thereby detecting mutations, insertions, or deletions within genes. Furthermore, utilize the Genome Analysis Toolkit (GATK) software package to analyze the genomic sequencing data.	Through study completion, an average of 6 moths
Secondary	Functional Assessment of Cancer Therapy-Breast	Utilize the FACT-B questionnaire to evaluate the quality of life of breast cancer patients in different medication intervention treatment groups before and after treatment. This questionnaire comprehensively assesses patients' performance in social interactions, emotional experiences, daily functioning, and physical condition, which indirectly reflects their overall quality of life.	Through study completion, an average of 6 moths
Secondary	Safety assessments	Evaluate to adverse events and serious adverse events.	Through study completion, an average of 6 moths