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

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

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.

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.

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