Neoadjuvant Tucidinostat and Exemestane in Early Breast Cancer

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: Tucidinostat
* Drug: Exemestane
* Drug: Ovarian function suppression


Participation Criteria
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Eligibility Criteria
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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.

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: Tucidinostat and Exemestane<br>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<br>* Tucidinostat: 30 mg BIW (Monday and Thursday) from week 3 to week 26<br>* Other names: Epidaza;Drug: Exemestane<br>* Exemestane: 25 mg QD from week 1 to week 26.<br>Drug: Ovarian function suppression<br>* If the patient is premenopausal, leuprorelin 3.75mg or goserelin 3.6 mg will be injected every 28 days.<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Tucidinostat, Estrogen Receptor-Positive, Neoadjuvant endocrine therapy