Clinical Study of Fulvestrant Combined With Chidamide in the Treatment of Hormone Receptor-positive Advanced Breast Cancer Resistant to CDK4/6 Inhibitors

Clinical Study of Fulvestrant Combined With Chidamide in the Treatment of Hormone Receptor-positive Advanced Breast Cancer Resistant to Cyclin-dependent Kinases（CDK）4/6 Inhibitors

The trial used a multicenter, open, single-arm design in which patients were treated with Chidamide combined with Fulvestrant.The primary objective is to evaluate the preliminary efficacy and safety of Chidamide in combination with Fulvestrant.Patients included in the trial were advanced breast cancer progressing on first-line aromatase inhibitor + Cyclin-dependent kinases（CDK）4/6i rescue therapy.

Study Overview

• Status: Not yet recruiting
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: Chidamide+ Fulvestrant

• Study Type: Interventional
• Enrollment (Anticipated): 20
• Phase: Phase 4

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• age ≥ 18 years, postmenopausal * female patients;
• histologically or cytologically confirmed hormone receptor positive (ER positive, PR positive or negative), human epidermal growth factor receptor 2 negative # breast cancer patients;
• the disease before enrollment is overall 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, previous progression by first-line aromatase inhibitors combined with Cyclin-dependent kinases（CDK）4/6 inhibitors;
• the total number of regimens regardless of rescue therapy or adjuvant therapy before enrollment is ≤ 3, of which the number of rescue chemotherapy regimens is ≤ 1;
• Eastern Collaborative Oncology Group（ECOG） score 0-1;
• absolute neutrophil count ≥ 1.5 × 109/L, platelets ≥ 100 × 109/L, hemoglobin ≥ 90 g/L;
• expected survival time ≥ 3 months;
• Voluntarily participate in this clinical trial and sign the written informed consent form

Exclusion Criteria:

• no measurable lesions (except simple bone metastasis), such as pleural or pericardial exudate, ascites, etc.;
• underwent major surgical procedures or significant trauma before enrollment, or patients are expected to undergo major surgical treatment;
• Patients who have previously been treated with fulvestrant or histone deacetylase inhibitors (including romidepsin, vorinostat), but have received only one cycle (≤ 2 times, d1, d15, respectively) of fulvestrant within 28 days (before enrollment) are allowed;
• known to have a history of allergy to the drug components of this protocol;
• the presence of brain (membrane) metastasis during the screening period;
• a history of immunodeficiency, including HIV test positive, or suffering from other acquired, congenital immunodeficiency diseases, or a history of organ transplantation;
• uncontrolled important cardiovascular disease;
• abnormal liver function [total bilirubin > 1.5 times the upper limit of normal; alanine aminotrans（ALT）/aspartate aminotransferase（AST） > 2.5 times the upper limit of normal in patients without liver metastasis, alanine aminotrans（ALT）/aspartate aminotransferase（AST） > 5 times the upper limit of normal in patients with liver metastasis], abnormal renal function (serum creatinine > 1.5 times the upper limit of normal);
• pregnant, lactating female patients or women of childbearing potential baseline pregnancy test positive; or during the study and the last dose of at least 8 to take effective contraceptive measures in subjects of childbearing age;
• According to the investigator's judgment, there are concomitant diseases that seriously endanger the patient's safety or affect the patient's completion of the study (such as: severe hypertension, diabetes, thyroid disease, active infection, etc.);
• History of definite neurological or psychiatric disorders, including epilepsy or dementia;
• Unsuitable for participation in the study as judged by the investigator.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

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

What is the study measuring?

Primary 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 16 months

Secondary 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 16 months
Overall Survival (OS)	Time from date of randomization to the date of death from any cause.	Up to approximately 38 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 16 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 16 months

Collaborators and Investigators

• Sponsor: Liaoning Tumor Hospital & Institute

Study record dates

Study Major Dates

• Study Start (Anticipated): February 7, 2022
• Primary Completion (Anticipated): July 30, 2022
• Study Completion (Anticipated): December 30, 2022

Study Registration Dates

• First Submitted: December 13, 2021
• First Submitted That Met QC Criteria: January 13, 2022
• First Posted (Actual): January 14, 2022

Study Record Updates

• Last Update Posted (Actual): January 14, 2022
• Last Update Submitted That Met QC Criteria: January 13, 2022
• Last Verified: January 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Physiological Effects of Drugs; Antineoplastic Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Hormone Antagonists; Estrogen Antagonists; Estrogen Receptor Antagonists; Fulvestrant
• Other Study ID Numbers: CSIIT-C10

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No