Tucidinostat and Fulvestrant in Hormone-receptor Positive Advanced Breast Cancer

Study Overview
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Brief Summary
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The purpose of the study is evaluate the efficacy and safety of tucidinostat in combination with fulvestrant in patients with hormone-receptor positive advanced breast cancer.

Detailed Description
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Hormone-receptor positive breast cancer is the most common subtype in breast cancer. Tucidinostat is an oral subtype-selective histone deacetylase inhibitor, which showed preliminary signs of encouraging anti-tumour activity in patients with advanced hormone-receptor positive breast cancer in the previous studies. The aim of this study is to evaluate the efficacy and safety of Tucidinostat in combination with fulvestrant in patients with recurrent or metastatic hormone-receptor positive breast cancer.

Official Title
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Trial of Tucidinostat in Combination With Fulvestrant in Patients With Hormone-receptor Positive Advanced Breast Cancer

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: Tucidinostat
* Drug: Fulvestrant


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Female patients aged 18-75 years (including cutoff value); The disease condition is inoperable, recurrent breast cancer, or metastatic breast cancer; Histological or cytological confirmation of hormone receptor-positive [estrogen receptor (ER) positive and progesterone receptors (PgR) positive or negative] breast cancer; At least one measurable lesion according to RECIST 1.1; Prior treatment: have not received systemic chemotherapy for recurrent or metastatic breast cancer; Eastern Cooperative Oncology Group Performance Status of 0-1; Adequate function of major organs meets the following requirements): Absolute Neutrophils count≥ 1.5×10^9/L; Platelets count≥ 90×10^9/L; Hemoglobin ≥ 90g/L; Total bilirubin≤ 1.5 × the upper limit of normal (ULN); ALT and AST ≤ 2.5 × ULN; BUN and Cr ≤ 1.5 × ULN; Left ventricular ejection fraction (LVEF) ≥ 50%; QTcF(Fridericia correction) ≤ 470 ms; International normalized ratio(INR)≤1.5 × ULN; activated partial thromboplastin time(APTT) ≤ 1.5 × ULN; Life expectancy ≥ 3 months; Have signed informed consent. Exclusion Criteria: Patients have untreated central nervous system (CNS) metastases; Patients with no measurable lesion according to RECIST 1.1; Patients with bilateral breast cancer; Patients with human epidermal growth factor receptor-2 (Her-2) positive; Recurrent or metastatic disease occurs within 2 years during adjuvant endocrine therapy; Patients previously received systemic chemotherapy for recurrent or metastatic breast cancer; Patients previously received any HDAC inhibitor or fulvestrant treatment; There are ascites, pleural effusion, pericardial effusion with clinical symptoms at baseline, those who need drainage, or those who have undergone drainage of serous effusion within 4 weeks before the first dose; Inability to swallow, intestinal obstruction or other factors affecting the administration and absorption of the drug; Patients with other invasive malignancies within 5 years or at the same time, with the exception of curatively-treated basal cell or squamous cell carcinoma of the skin or cervical carcinoma in situ; Patients with a history of allergies to the drug components of this regimen; Patients with active HBV and HCV infection; stable hepatitis B after drug treatment (HBV virus copy number is higher than the upper limit of reference value) and cured hepatitis C patients (HCV virus copy number exceeds the lower limit of detection method) can be included; Patients with a history of immunodeficiency, including HIV positive, or other acquired or congenital immunodeficiency disease, history of organ transplantation; Patients have uncontrolled or significant cardiovascular disease, including: Myocardial infarction (< the last 12 months); Uncontrolled angina (< the last 6 months); Congestive heart failure (< the last 6 months), or Left Ventricular Ejection Fraction (LVEF) < 50% prior to study entry; Any mental or cognitive disorder, that would interfere the ability to understand the informed consent document or the operation and compliance of study; Any other condition which is inappropriate for the study in the opinion of the investigators.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: Tucidinostat + Fulvestrant<br>Patients receive 30 mg Chidamide twice per week. Fulvestrant 500mg (2 syringes of Fulvestrant 250mg), Fulvestrant 500 mg i.m. every 28 (+/- 3) days plus an additional 500 mg on day 14 (+/-3) of first month only. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. | Drug: Tucidinostat<br>* 30 mg, administered orally twice per week (BIW)<br>Drug: Fulvestrant<br>* Fulvestrant was supplied as a castor oil based solution in clear neutral glass pre-filled syringes. Each syringe will contain 250 mg of fulvestrant in 5 ml.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival (PFS) | PFS was defined as the time from treatment until objective disease progression according to Response Evaluation Criteria in Solid Tumours version 1.1 (RECIST 1.1), or death by any cause, whichever is first met. | From date of treatment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 3 years. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| overall survival (OS) | Defined as from the date of treatment to date of death, irrespective of cause. | Time from treatment to death from any cause, assessed up to 3 years. | 
| Objectivel response rate (ORR) | Defined as numbers of patients achieved complete response and partial response of treatment. | Response is assessed once every 8 weeks, from the day of treatment to the date of first documented progression, assessed up to 3 years. | 
| Duration of response (DOR) | Defined as from the first date when criteria for response is met until the first date when the criteria for progression or death is met. | From the day of treatment to the date of first documented progression, assessed up to 3 years. | 
| 4.Clinical Benefit Rate (CBR) | ORR is defined as percentage of participants with Complete Response, Partial Response or Stable Disease≥24 weeks, assessed by the investigators according to the RECIST v1.1. | From the day of treatment to the date of first documented progression, assessed up to 3 years. | 
| Adverse event(AE) | Adverse event related to treatment. | From the day of treatment to the date of first documented progression, assessed up to 3 years. |