Overview

Entinostat in Chinese Postmenopausal Women Patients With Locally Recurrent or Metastatic Breast Cancer

Status:
Completed
Trial end date:
2018-07-18
Target enrollment:
0
Participant gender:
Female
Summary
The purpose of this study is to evaluate the safety and tolerance of entinostat administered orally as a single agent in a weekly dosing schedule. Additionally, this study will characterize the pharmacokinetics parameters in Chinese postmenopausal women with advanced breast cancer. And to define the profile of adverse events, including laboratory parameters in these subjects
Phase:
Phase 1
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
EddingPharm Oncology Co., LTD.
Taizhou EOC Pharma Co., Ltd.
Treatments:
Entinostat
Exemestane
Histone Deacetylase Inhibitors
Criteria
Inclusion Criteria:

For inclusion in the study patients should fulfil the following criteria:

- Provision of informed consent prior to any study specific procedures.

- Postmenopausal women aged ≤ 65years.

- Estrogen receptor (ER) and / or progesterone receptor (PR) positive breast cancer
confirmed by pathology.

- Once received a non-steroidal aromatase inhibitor (letrozole / anastrozole) treatment,
the disease recurrence or progression of breast cancer currently.

- Patients must have Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1.
And recently (past 2 months), weight loss is no more than 10% of average weight.

- Patients must have a life expectancy >3 months.

- Patients must have adequate organ and bone marrow function as defined by the following
laboratory results.

1. .absolute neutrophil count ( ANC )≥ 1,500 /mm3

2. . Platelets≥100,000 /mm3

3. . White blood cell count(WBC) ≥ 3,000 /mm3

4. . Hemoglobin ≥ 9 g/dL.

5. . Creatinine ≤ 1.5 times the upper limit of normal (ULN) for the institution or
Creatinine clearance ≥ 60 ml/min/1.73m2

6. . Total bilirubin ≤ 1.5 times the upper limit of normal for the institution(ULN)

7. .Aspartate transaminases (AST/SGOT) or alanine transaminase (ALT/SGPT) ≤ 2.5
times the upper limit.

- Patients must be able to take drugs and don't spit out, no malabsorption problem.

- Able to comply with study procedures and follow-up examinations.

Exclusion Criteria:

- Patients have known central nervous system metastasis except patients who have
terminated steroid treatment for brain metastasis or spinal cord compression with
remain disease stable for at least 1 month.

- Previous treatment with entinostat or any other histone deacetylase inhibitor
(Valproic acid, Chidamide etc).

- Known allergy to any ingredients of entinostat and other drugs in the same class.

- Women who are pregnant or breast-feeding (premenopausal). For women of childbearing
potential, agreement to use a medically approved contraception measures (such as the
intrauterine device (IUD), birth control pills or condoms) and to continue its use for
the duration of study treatment and for 3 months after the last dose of study
treatment.

- Had received chemotherapy/radiotherapy or other anticancer therapy during the study or
within 4 weeks of start of study treatment. Patients must completely recovered from
all adverse events due to previous agents administered before 4 weeks (except
alopecia).

- Major surgery within 28 days of start of study treatment.

- Patients have serious or uncontrolled systemic disease (such as severe liver
dysfunction, severe renal dysfunction, poorly controlled diabetes, poorly controlled
acute infections). Unstable or decompensated respiratory or cardiovascular disease, or
peripheral vascular disease (including diabetic vascular disease), or organ
transplantation.

- Received potent CYP1A2 or CYP3A4 inducer and/or inhibitor (including but not limited
following drug: ketoconazole, rifampicin, atazanavir, Clarithromycin, indinavir,
itraconazole, nelfinavir, saquinavir, telithromycin, voriconazole, grapefruit or
grapefruit juice, rifabutin, phenytoin, Carbamazepine and phenobarbital).

- Patients with another active cancer (excluding basal cell carcinoma or cervical
intraepithelial neoplasia [cervical intraepithelial neoplasia (CIN)/cervical carcinoma
in situ] or melanoma in-situ). Prior history of other cancer is allowed, as long as
there is no active disease within the prior 5 years.

- Active bleeding or new thrombotic diseases using of anticoagulant drugs, patients with
bleeding tendency.

- Meet with any of the following criteria about cardiac parameters:

- the corrected QT interval (QTc) >470 msec under resting conditions.

- myocardial infarction or arterial thrombosis events within 6 months, or experiencing
severe or unstable angina, or New York Heart Association (NYHA) Class III or IV
disease.

- Resting ECG imply any clinically significant abnormal on rhythm, conduction and
morphology, for example, left bundle branch block, third degree heart block, second
degree heart block, PR interval > 250 msec.

- Any factors (such as, heart failure, hypokalemia, inherited long QT syndrome, acquired
long QT syndrome or family history of unexplained sudden death in immediate family
members under 40 years old) or known combined drug (such as, sotalol, cisapride,
clozapine, amiodarone and erythromycin, etc.) to increase risk of prolongation of QTc
interval or arrhythmic event.

- History of or known human immunodeficiency virus (HIV) infection

- Known drug or long-term alcoholics.

- Patient is currently enrolled in (or completed within 30 days before study drug
administration) another investigational drug study.

- Involvement in the planning and conduct of the study.

- Possible of lower inclusion criteria according to the researchers (such as weak, etc),
or the other is not suitable for this study.