Clinical Study of Chidamide Combined With Fulvestrant in the Treatment of Hormone Receptor-positive Advanced Breast Cancer

Study Overview
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Brief Summary
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This is a Open-label study of chidamide in combination with fulvestrant for the treatment of postmenopausal women with hormone receptor positive, Her2 negative, advanced breast cancer who have received no or only one line of endocrine therapy for advanced breast cancer.

Official Title
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Clinical Study of Chidamide Combined With Fulvestrant in the Treatment of Hormone Receptor-positive Advanced Breast Cancer

Conditions
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Advanced Breast Cancer

Intervention / Treatment
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* Drug: Chidamide
* Drug: Fulvestrant


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: women aged ≥ 18 years, histologically or cytologically confirmed HR positive (ER expression ≥ 10%, PR positive or negative), HER2 negative breast cancer patients; before enrollment for unresectable locally advanced or metastatic breast cancer, and at least one measurable lesion or no measurable lesion and bone metastasis alone patients; For locally advanced or metastatic breast cancer, no previous endocrine therapy or first-line endocrine therapy, and no previous use of CDK4/6 inhibitors. Specifically, it includes the following conditions: Cohort 1: (neo) recurrence > 12 months after the end of adjuvant endocrine therapy, and without any rescue therapy · newly diagnosed advanced breast cancer without any rescue therapy Cohort 2: (neo) recurrence during or ≤ 12 months after the completion of adjuvant endocrine therapy, and without any rescue therapy · recurrence > 12 months after the completion of adjuvant endocrine therapy, and progression by first-line endocrine therapy · newly diagnosed advanced breast cancer and progression by first-line endocrine rescue therapy Cohort 1 without previous chemotherapy for advanced breast cancer; Cohort 2 with ≤ 1 previous chemotherapy for advanced breast cancer; no brain metastasis or asymptomatic brain metastasis; ECOG score 0-1; Absolute neutrophil count ≥ 1.5 × 109/L, platelet ≥ 100 × 109/L, hemoglobin ≥ 90 g/L; Expected survival time ≥ 3 months; Voluntarily participate in this clinical trial, sign the written informed consent; Exclusion Criteria: no measurable lesions (except bone metastases alone), such as pleural or pericardial exudates, ascites, etc. Patients who have undergone major surgical procedures or significant trauma before enrollment, or are expected to undergo major surgical treatment Patients who have previously been treated with CDK4/6 inhibitors, fulvestrant or HDAC inhibitors (including romidepsin, vorinostat, berlistat, parabrestat), but have received 1 cycle (≤ 2 times, on d1, d15, respectively) of fulvestrant within 28 days (before enrollment) are allowed Known history of allergy to the drug components of this protocol Meningeal metastasis before enrollment Uncontrollable serosal effusion Active infection [an active bacterial, viral, fungal, mycobacterial, parasitic or other infection (excluding fungal infections of the nail bed) within 4 months prior to Screening or any major infectious event requiring intravenous antibiotics, or targeted antiviral therapy, or hospitalization], or persistent fever within 14 days prior to Screening a history of immunodeficiency, including HIV test positive, or suffering from other acquired, congenital immunodeficiency diseases, or a history of organ transplantation; according to the investigator's judgment, there are serious hazards to the patient's safety, or affect the patient to complete the study of concomitant diseases (such as: severe hypertension, diabetes, thyroid disease, active infection, etc.); History of definite neurological or psychiatric disorders, including epilepsy or dementia Subjects who, in the opinion of the investigator, are not suitable for the study

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: chidamide + fulvestrant<br> | Drug: Chidamide<br>* chidamide 30mg orally，Biw<br>Drug: Fulvestrant<br>* Fulvestrant 500mg i.m. injections every 28 days (Cycle n Day 1) with 1 additional dose on Day 15 of Cycle 1<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Response Rate (ORR) | Overall response rate (ORR) is defined as the proportion of patients with the best overall response of complete response (CR) or partial response (PR) according to RECIST 1.1. | Up to approximately 26 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival (PFS) | PFS is defined as the time from the date of randomization to the date of the first documented progression or death due to any cause. | Up to approximately 26 months | 
| Overall Survival (OS) | Time from date of randomization to the date of death from any cause. | Up to approximately 58 months | 
| Clinical Benefit Rate (CBR) | Clinical benefit rate (CBR), defined as the proportion of patients with a best overall response of complete response (CR) or partial response (PR) or stable disease (SD) lasting 24 weeks or longer as defined in RECIST 1.1. | Up to approximately 26 months | 
| Duration of Response (DOR) | Time from the first documented response (CR or PR) to the first documented progression or death due to underlying cancer as defined in RECIST 1.1. | Up to approximately 26 months |