Clinical Study of Huaier Granules in Patients With Advanced Breast Cancer Without Visceral Metastasis

Study Overview
=================
Brief Summary
-----------------
This is a multicenter, open-label, randomized controlled, prospective clinical study to evaluate the efficacy and safety of Huaier Granules in patients with advanced breast cancer without visceral metastasis.

Detailed Description
-----------------
This study used a blank control design and included at least 384 subjects. The experimental group and control group were randomized in a 2:1 ratio (at least 256 subjects in the experimental group and at least 128 subjects in the control group). Patients in the experimental group were treated with Huaier Granules (10g/dose, 3 times/day), while undergoing routine diagnosis and treatment; The control group received routine diagnosis and treatment, but did not take Huaier granules until the subjects experienced disease progression or intolerance.

Official Title
-----------------
A Multicenter, Open-label, Randomized, Controlled, Prospective Clinical Study of Huaier Granules in Patients With Advanced Breast Cancer Without Visceral Metastasis

Conditions
-----------------
Breast Cancer Stage IV

Intervention / Treatment
-----------------
* Drug: Huaier Granule


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: 18 years old ≤ age ≤ 75, regardless of gender. For breast cancer patients who are clinically or pathologically diagnosed as non visceral metastasis, if the patient has only local recurrence or metastasis, the clinician judges that it is not suitable or refuses to use local treatment with radical intensity, such as surgical resection or radiotherapy. Prior to enrollment, no more than first-line chemotherapy/endocrine therapy/targeted therapy/immunotherapy were allowed;If the patient has previously received first-line therapy, the outcome of treatment should be clinically assessed as disease progression or intolerance. There is at least one measurable lesion that meets the RECIST 1.1 standard, or only bone metastases (including osteolytic lesions or mixed lesions). The liver and kidney functions meet the following conditions: AST and ALT<3 ULN, total bilirubin ≤ 2 ULN, and blood creatinine<1.5 ULN. Other laboratory tests meet the following requirements: Hb ≥ 9g/dl, platelet count ≥ 60 × 10^9/L, absolute neutrophil count>1.0 × 10^9/L. Expected survival time ≥ 12 weeks. The patient's ECOG physical state score is 0 or 1. The subjects participated in the study voluntarily and signed an informed consent form. Exclusion Criteria: Any other malignancies diagnosed within 5 years prior to enrollment, except those with a low risk of metastasis and death (5-year survival > 90%), such as adequately treated basal cell or squamous cell skin cancer or cervical carcinoma in situ. There is visceral metastasis of breast cancer. Patients with advanced (local recurrence or metastasis) breast cancer who plan to receive radical local treatment. Serious infections (CTCAE>Level 2) have occurred within 4 weeks prior to enrollment, such as severe pneumonia, bacteremia, infection complications that require hospitalization; Symptoms and signs of infection or the need for oral or intravenous antibiotic treatment within 2 weeks prior to enrollment, except for prophylactic use of antibiotics. Suffering from severe acute and chronic diseases. Suffering from severe diabetes whose blood sugar cannot be effectively controlled. Patients who cannot take oral medication or are allergic to the ingredients of Huaier granules. Drug abusers, or those who suffer from psychological or mental illnesses that may interfere with research compliance. Pregnant or lactating women. The researcher believes that it is not suitable to participate in this study.

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

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Huaier Granule+Standard treatment<br>The subject is administered according to the clinical dosage and method of medication until disease progression occurs or the subject is unable to tolerate treatment.Subjects receiving routine diagnosis and treatment simultaneously. | Drug: Huaier Granule<br>* 10g each time, three times a day<br>* Other names: Z20000109（NMPA Approval Number）;|
| No Intervention: Standard treatment<br>Subjects receive routine diagnosis and treatment without taking Huaier granules. | |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Investigator evaluated progression free survival | The time from randomization to the first occurrence of disease progression or death from any cause. As long as the subject experiences either disease progression or death first, it reaches the endpoint of the study | start of treatment until 3.5-year follow-up | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival(OS) | The time from randomization to death (from any cause) | start of treatment until 3.5-year follow-up | 
| Clinical benefit rate (CBR) | The percentage of patients with advanced breast cancer who achieved a complete response, partial response, or stable disease for at least six months after treatment | start of treatment until 3.5-year follow-up | 
| Objective response rate (ORR) | Proportion of patients whose breast cancer has shrunk to a predetermined volume and maintains a minimum time limit | start of treatment until 3.5-year follow-up | 
| Adverse reactions | Harmful reactions of Huaier granules that are unrelated to the purpose of the medication under normal usage and dosage | start of treatment until 3.5-year follow-up | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
non-visceral metastasis, Huaier granule, randomized controlled, prospective clinical study