NeoTEE: Neoadjuvant Tucidinostat and Exemestane in Early Breast Cancer

Sponsor

First Affiliated Hospital, Sun Yat-Sen University (Other)

Overall Status

Unknown status

CT.gov ID

NCT04465097

Collaborator

(none)

Enrollment

Location

Arm

24.7

Anticipated Duration (Months)

1.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Breast Cancer	Drug: Tucidinostat Drug: Exemestane Drug: Ovarian function suppression	Phase 2

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 Design

Study Type:

Interventional

Anticipated Enrollment :

30 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Jul 8, 2020

Anticipated Primary Completion Date :

Jul 31, 2021

Anticipated Study Completion Date :

Jul 31, 2022

Arms and Interventions

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: Chidamide Epidaza 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.

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:

Chidamide

Epidaza

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.

Outcome Measures

Primary Outcome Measures

objective response rate (ORR) evaluated by MRI [Up to 31 weeks]
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)

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

Inclusion Criteria:

Written informed consent must be signed；
Eastern Cooperative Oncology Group Performance Status: 0~1;
Histological confirmation of estrogen receptor (ER) positive and HER 2 negative invasive breast cancer;
Age ≥18 years old；
No distant metastatic disease；
The disease condition is stage II or stage III;
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:

Patients who are pregnant or lactating at the time of randomization or refuse to contraception.
Patients who received organ transplantation (include bone marrow autologous transplantation and stem cell transplantation).
Patients who have other malignant diseases within 5 years, except for cured skin basal cell carcinoma, flat cell carcinoma or cervical carcinoma in situ
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.
Patients with sever hepatic, renal,cardiovascular, respiratory, digestive diseases or uncontrolled diabetes.
Patients who had myocardial infarction in the past 12 months.
Patients who participate in other clinical trail.
Patients who allergy to goserelin, leuprorelin, tucidinostat or aromatase inhibitor.