Neoadjuvant Chemotherapy With or Without Huaier Granule in Treating Women With Locally Advanced Breast Cancer That Can Be Removed By Surgery

Study Overview
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Brief Summary
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RATIONALE: Huaier (Trametes robiniophila Murr) is a traditional Chinese medicine, which has been widely used in China for many years. The investigators have found that Huaier could exert synergistic effects with Epirubicin, Cyclophosphamide, and Paclitaxel on breast cancer cells. It is not yet known whether combination chemotherapy is more effective when given together with Huaier in the neoadjuvant setting . PURPOSE: To evaluate the effects of treatment with Huaier Granule in managing locally advanced breast cancers with synergistic action of the neoadjuvant chemotherapy.

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: Huaier Granule
* Drug: Epirubicin
* Drug: Docetaxel
* Drug: Cyclophosphamide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age: ≥ 18, female; Breast cancer (TNM II, III, IV) larger than 2cm in maximal diameter able to benefit from neoadjuvant chemotherapy; Ductal or lobular histological type of the breast tumor; The diagnosis and breast cancer has been confirmed by pathological examination; The liver and kidney function satisfies the following conditions within 3 days after surgery (excluding day 3): aspartate aminotransferase (AST), glutamic-oxalacetic transaminase (ALT) < 2 upper limit of normal (ULN), total bilirubin ≤ 1.5 ULN, serum creatinine < 1.5 ULN; Other laboratory tests meet the following requirements within 3 days after surgery (excluding day 3): Hb ≥ 90g/l, platelet count ≥ 100×109/L, absolute neutrophil count > 1.5×109/L; The expected survival time ≥ 8 months; The subjects volunteer to sign the informed consent. Exclusion Criteria: Breast cancers of rare histological type (other than ductal and lobular); Noninvasive cancer; Presence of organ, bone, or skin metastases; Pregnant or lactating women; Those with active bleeding due to various reasons; Those with HIV infection or AIDS-associated diseases; Those with severe acute and chronic diseases; Those with severe diabetes; Those with serious infectious diseases; Those who can not take drugs by oral route; Drug abusers or those with psychological or mental diseases that may interfere with study compliance; Conditions that are considered not suitable for this study investigators

Ages Eligible for Study
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Minimum Age: 18 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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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Docetaxel, Epirubicin and Cyclophosphamide (TEC)<br>Six cycles of docetaxel (75 mg/m²), epirubicin (70 mg/m²) and cyclophosphamide (600 mg/m²). Patients will be treated with chemotherapy every 3 weeks (+/- 2 days ) in total. Huaier Granule will be not be administrated. | Drug: Epirubicin<br>* 70 mg/m² ivdrip, d1 for both TEC and ET regimes<br>Drug: Docetaxel<br>* 75 mg/m² ivdrip, d2 for both TEC and ET regimes<br>Drug: Cyclophosphamide<br>* 600 mg/m² ivdrip, d2 for TEC regimes<br>|
| Experimental: Docetaxel, Epirubicin and Cyclophosphamide + Huaier (TEC+HE)<br>Six cycles of docetaxel (75 mg/m²), epirubicin (70 mg/m²) and cyclophosphamide (600 mg/m²). Patients will be treated with chemotherapy every 3 weeks (+/- 2 days ) in total. Huaier Granule will be administrated from the first cycle of chemotherapy until time of definitive surgery. | Drug: Huaier Granule<br>* 20g tid, orally<br>Drug: Epirubicin<br>* 70 mg/m² ivdrip, d1 for both TEC and ET regimes<br>Drug: Docetaxel<br>* 75 mg/m² ivdrip, d2 for both TEC and ET regimes<br>Drug: Cyclophosphamide<br>* 600 mg/m² ivdrip, d2 for TEC regimes<br>|
| Experimental: Epirubicin and Docetaxel (ET)<br>Six cycles of epirubicin (70 mg/m²) and docetaxel (75 mg/m²). Patients will be treated with chemotherapy every 3 weeks (+/- 2 days ) in total. Huaier Granule will be not be administrated. | Drug: Epirubicin<br>* 70 mg/m² ivdrip, d1 for both TEC and ET regimes<br>Drug: Docetaxel<br>* 75 mg/m² ivdrip, d2 for both TEC and ET regimes<br>|
| Experimental: Epirubicin and Docetaxel+Huaier (ET+HE)<br>Six cycles of epirubicin (70 mg/m²) and docetaxel (75 mg/m²). Patients will be treated with chemotherapy every 3 weeks (+/- 2 days ) in total. Huaier Granule will be administrated from the first cycle of chemotherapy until time of definitive surgery. | Drug: Huaier Granule<br>* 20g tid, orally<br>Drug: Epirubicin<br>* 70 mg/m² ivdrip, d1 for both TEC and ET regimes<br>Drug: Docetaxel<br>* 75 mg/m² ivdrip, d2 for both TEC and ET regimes<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pathologic complete response (pCR) | A pCR in the breast was defined as no pathologic evidence of invasive disease (residual ductal carcinoma in situ (DCIS) or lobular carcinoma in situ (LCIS) was allowed). | one month after operation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical Complete Response (cCR) | A cCR was defined as achieving either a Complete Response (CR) or a Partial Response (PR) using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. CR was defined as the disappearance of all target lesions, and PR was defined as at least a 30% decrease in the sum of the longest diameter (LD) of target lesions taking as reference the baseline sum LD. | one month after the neoadjuvant chemotherapy | 
| Disease-free survival (DFS) | DFS was defined as the date of definitive surgery until the date of recurrence, metastasis, appearance of a second primary tumor, or death from any cause, whichever occurs first, assessed up to 10 years. | up to 10 years | 
| Overall survival (OS) | OS was defined as the date of definitive surgery until the date of death from any cause, assessed up to 10 years. | up to 10 years |