Study of the Effect of the Addition of SNDX-275 (Entinostat) to Continued Aromatase Inhibitor (AI) Therapy in Postmenopausal Women With ER+ Breast Cancer Whose Disease is Progressing

NCT ID: NCT00828854

Last Updated: 2022-06-30

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 27 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-10-01
• Study Completion Date: 2009-11-24

Brief Summary

The addition of entinostat to an AI will result in a maximal abrogation of estrogen receptor-α mediated activity and inhibit mechanisms of resistance to the aromatase inhibitor.

It is hypothesized that entinostat with continued AI will increase the estimated AI clinical benefit rate (CBR) from 5% to 25% with an acceptable safety profile.

Conditions

ER+ Breast Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Entinostat 5 mg + AI

Entinostat 5 mg tablet orally every week on Days 1, 8. 15 and 22 of each 28-day treatment cycle in combination with continued treatment with AI therapy at labeled dose and schedule until disease progression or unacceptable toxicity.

Group Type: EXPERIMENTAL

Entinostat

Intervention Type: DRUG

Entinostat 5 mg PO every week

Aromatase Inhibitor (AI) Therapy

Intervention Type: DRUG

AI therapy at labeled dose and schedule as prescribed in clinical practice. AI therapies include: Arimidex® (anastrozole) 1 mg/day by mouth (PO), Fermara® (letrozole) 2.5 mg/day PO , Aromasin® (exemestane) 25 mg/day PO.

Interventions

Entinostat

Entinostat 5 mg PO every week

Intervention Type: DRUG

Aromatase Inhibitor (AI) Therapy

AI therapy at labeled dose and schedule as prescribed in clinical practice. AI therapies include: Arimidex® (anastrozole) 1 mg/day by mouth (PO), Fermara® (letrozole) 2.5 mg/day PO , Aromasin® (exemestane) 25 mg/day PO.

Intervention Type: DRUG

Other Intervention Names

SNDX-275

Eligibility Criteria

Inclusion Criteria

1. Postmenopausal female patients.

2. Histologically or cytologically confirmed estrogen receptor-positive (ER+) breast cancer.

3. Progressive disease (PD) after at least 3 months on treatment with a 3rd generation AI in the advanced disease setting as measured by Response Evaluation Criteria in Solid Tumors (RECIST) criteria.

4. At least 1 measurable lesion ≥ 20 mm by conventional techniques or ≥ 10 mm by spiral computed tomography (CT) scan with the last imaging performed within 4 weeks prior to study entry. If there is only one measurable lesion and it is located in previously irradiated field, it must have demonstrated progression according to RECIST criteria.

5. Eastern Cooperative Oncology Group (ECOG) 0-1.

6. Laboratory parameters:

1. Hemoglobin ≥ 9.0 g/dL; platelets ≥ 100 x10^9/L; absolute neutrophil count (ANC) ≥ 1.5 x 10^9/L without the use of hematopoietic growth factors.

2. Creatinine less than 2.5 times the upper limit of normal for the institution.

3. aspartate aminotransferase (AST) and alanine aminotransferase (ALT) less than 2.5 times the upper limit of normal for the institution.

7. Able to understand and give written informed consent and comply with study procedures.

Exclusion Criteria

1. Discontinuation of AI therapy prior to study entry.

2. Less than 3 months treatment with most recent AI.

3. Rapidly progressive, life-threatening metastases, including any of the following:

1. Symptomatic lymphangitic metastases.

2. Patients with known active brain or leptomeningeal involvement.

4. More than one prior chemotherapy for metastatic disease.

5. Any chemotherapy within 3 months prior to study.

6. Radiotherapy to measurable lesion within 2 months prior to study.

7. Bisphosphonates initiated within 4 weeks prior to study start.

8. Allergy to benzamides or inactive components of study drug.

9. Previous treatment with entinostat or any other histone deacetylase (HDAC) inhibitor including valproic acid.

10. Patient is currently receiving treatment with any agent listed on the prohibited medication list such as valproic acid or other systemic cancer agents

11. Any concomitant medical condition that precludes adequate study treatment compliance or assessment, or increases patient risk in the opinion of the investigator:

1. Myocardial infarction or arterial thromboembolic events within 6 months, or experiencing severe or unstable angina, New York Heart Association (NYHA) Class III or IV disease and a QTc interval >0.47 second.

2. Uncontrolled heart failure or hypertension, uncontrolled diabetes mellitus, uncontrolled systemic infection,

3. Other active malignancy within 5 years excluding basal cell carcinoma or cervical intraepithelial neoplasia [CIN / cervical carcinoma in situ] or melanoma in situ).

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

• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Syndax Pharmaceuticals

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

St. Vincent's University Hospital

Dublin, , Ireland

The University of Birmingham

Birmingham, , United Kingdom

Velindre Hospital - Whitchurch

Cardiff, , United Kingdom

Whiston Hospital; Clatterbridge Centre for Oncology

Liverpool, , United Kingdom

University College London Hospitals

London, , United Kingdom

Christie Hospital, Manchester Breast Centre

Manchester, , United Kingdom

Countries

Ireland; United Kingdom

Other Identifiers

SNDX-275-0303

Identifier Type: -

Identifier Source: org_study_id