Neoadjuvant Tucidinostat and Exemestane in Early Breast Cancer (NeoTEE)

Neoadjuvant Tucidinostat and Exemestane in Estrogen Receptor-Positive Early Breast Cancer （NeoTEE）

This study is to evaluate the efficacy of tucidinostat combined with exemestane as neoadjuvant strategy in estrogen receptor-positive early breast cancer patients and explore the genetic model which can predict neoadjuvant endocrine therapeutic results.

Study Overview

• Status: Completed
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: Tucidinostat; Drug: Exemestane; Drug: Ovarian function suppression

Detailed Description

This study is to evaluate the efficacy of tucidinostat combined with exemestane as neoadjuvant strategy in estrogen receptor-positive early breast cancer patients.This study will recruit 30 patients. The 30 patients will receive 25 mg exemestane QD for 26 weeks. Tucidinostat will be prescribed 30 mg BIW from week 3 to week 26. During neoadjuvant treatment biopsy, CEUS and MRI will be perfomed according to protocol to evaluate the therapeutic results. Genetic testing will also be performed before and after neoadjuvant treatment to explore the predictive value. MRI evaluated ORR is primary end point. CEUS evaluated ORR, pCR, AE and RCB are secondary end point.

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510000
      • The First Affiliated Hospital of Sun Yat-sen University

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Written informed consent must be signed；
2. Eastern Cooperative Oncology Group Performance Status: 0~1;
3. Histological confirmation of estrogen receptor (ER) positive and HER 2 negative invasive breast cancer;
4. Age ≥18 years old；
5. No distant metastatic disease；
6. The disease condition is stage II or stage III;
7. Laboratory exam criteria for enrollment: HGB≥10g/dl, WBC≥4,000/mm3, PLT≥100,000/mm3, GOT, GPT, ALP≤2 times ULN, TBIL, CCr≤1.5 times ULN.

Exclusion Criteria:

1. Patients who are pregnant or lactating at the time of randomization or refuse to contraception.
2. Patients who received organ transplantation (include bone marrow autologous transplantation and stem cell transplantation).
3. Patients who have other malignant diseases within 5 years, except for cured skin basal cell carcinoma, flat cell carcinoma or cervical carcinoma in situ
4. Patients with psychiatric disorder, peripheral or central nerve system disease or any disorder, which compromises ability to give informed consent or participate in this study.
5. Patients with sever hepatic, renal,cardiovascular, respiratory, digestive diseases or uncontrolled diabetes.
6. Patients who had myocardial infarction in the past 12 months.
7. Patients who participate in other clinical trail.
8. Patients who allergy to goserelin, leuprorelin, tucidinostat or aromatase inhibitor.

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: Tucidinostat and Exemestane; Patients receive exemestane from week 1 to week 26 and Tucidinostat BIW from week 3 to week 26. Courses continue in the absence of disease progression or unacceptable toxicity. If the patient is premenopausal, leuprorelin or goserelin will be prescribed.	Drug: Tucidinostat; Tucidinostat: 30 mg BIW (Monday and Thursday) from week 3 to week 26; Other Names: Epidaza; Chidamide; Drug: Exemestane; Exemestane: 25 mg QD from week 1 to week 26.; Drug: Ovarian function suppression; If the patient is premenopausal, leuprorelin 3.75mg or goserelin 3.6 mg will be injected every 28 days.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
objective response rate (ORR) evaluated by MRI	ORR is defined as percentage of participants with Complete Response and Partial Response, assessed by the investigators using MRI according to the Response Evaluation Criteria in Solid Tumors (RECIST)	Up to 31 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
objective response rate (ORR) evaluated by CEUS	Contrast-enhanced ultrasound will also be performed to assess ORR	Up to 31 weeks
pathologic complete response rate (pCR)	The percentage of participants with pathologically assessed ypT0 and ypTis of breast disease.	Up to 31 weeks
Adverse effect (AE)	All advese effect events related with Tucidinostat and Exemestane.	Up to 31 weeks
Residual Cancer Burden (RCB)	Pathologilly assessed residual cancer burden according to MD Anderson protocol.	Up to 31 weeks

Collaborators and Investigators

• Sponsor: First Affiliated Hospital, Sun Yat-Sen University
• Investigators: Principal Investigator: Ying Lin, MD, First Affiliated Hospital, Sun Yat-Sen University

Publications and helpful links

General Publications

• Jiang Z, Li W, Hu X, Zhang Q, Sun T, Cui S, Wang S, Ouyang Q, Yin Y, Geng C, Tong Z, Cheng Y, Pan Y, Sun Y, Wang H, Ouyang T, Gu K, Feng J, Wang X, Wang S, Liu T, Gao J, Cristofanilli M, Ning Z, Lu X. Tucidinostat plus exemestane for postmenopausal patients with advanced, hormone receptor-positive breast cancer (ACE): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2019 Jun;20(6):806-815. doi: 10.1016/S1470-2045(19)30164-0. Epub 2019 Apr 27.

Study record dates

Study Major Dates

• Study Start (Actual): July 8, 2020
• Primary Completion (Actual): October 1, 2023
• Study Completion (Actual): October 1, 2023

Study Registration Dates

• First Submitted: June 30, 2020
• First Submitted That Met QC Criteria: July 7, 2020
• First Posted (Actual): July 9, 2020

Study Record Updates

• Last Update Posted (Actual): October 17, 2023
• Last Update Submitted That Met QC Criteria: October 15, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: Estrogen Receptor-Positive; Neoadjuvant endocrine therapy; Tucidinostat
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Hormone Antagonists; Aromatase Inhibitors; Steroid Synthesis Inhibitors; Estrogen Antagonists; Exemestane
• Other Study ID Numbers: 20200628GD

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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