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

NCT00828854 | Completed Phase 2 Results DMC

• 1 other identifier: SNDX-275-0303
• Study Type: interventional
• Target: 27
• Locations: 2 countries
• Sites: 6

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

Keywords

breast cancer; estrogen receptor positive

Outcome Measures

Primary Outcomes (1)

• Clinical Benefit Rate (CBR)

  CBR is defined as the percentage of participants who achieved complete response (CR) or partial response (PR) or stable disease (SD) for 6 months as assessed by the investigator based on Response Evaluation Criteria in Solid Tumors (RECIST), version 1.0. CR is defined as the disappearance of all target lesions. PR is defined as at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD. SD is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking as reference the smallest sum LD since the treatment started.

  6 months

Secondary Outcomes (3)

• Progression-Free Survival (PFS)

  Up to 6, 28-day cycles

• Objective Response Rate (ORR) During the First 6 Cycles of Study Treatment

  Up to 6, 28-day cycles

• Number of Participants With Adverse Events (AEs)

  Up to 6, 28-day cycles + 30 days

Study Arms (1)

Entinostat 5 mg + AI

EXPERIMENTAL

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.

Drug: Entinostat; Drug: Aromatase Inhibitor (AI) Therapy

Interventions

Entinostat DRUG

Entinostat 5 mg PO every week

Also known as: SNDX-275

Entinostat 5 mg + AI

Aromatase Inhibitor (AI) Therapy 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.

Entinostat 5 mg + AI

Eligibility Criteria

• Sex: female
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Postmenopausal female patients.
• Histologically or cytologically confirmed estrogen receptor-positive (ER+) breast cancer.
• 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.
• 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.
• Eastern Cooperative Oncology Group (ECOG) 0-1.
• Laboratory parameters:
• 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.
• Creatinine less than 2.5 times the upper limit of normal for the institution.
• aspartate aminotransferase (AST) and alanine aminotransferase (ALT) less than 2.5 times the upper limit of normal for the institution.
• Able to understand and give written informed consent and comply with study procedures.

You may not qualify if:

• Discontinuation of AI therapy prior to study entry.
• Less than 3 months treatment with most recent AI.
• Rapidly progressive, life-threatening metastases, including any of the following:
• Symptomatic lymphangitic metastases.
• Patients with known active brain or leptomeningeal involvement.
• More than one prior chemotherapy for metastatic disease.
• Any chemotherapy within 3 months prior to study.
• Radiotherapy to measurable lesion within 2 months prior to study.
• Bisphosphonates initiated within 4 weeks prior to study start.
• Allergy to benzamides or inactive components of study drug.
• Previous treatment with entinostat or any other histone deacetylase (HDAC) inhibitor including valproic acid.
• Patient is currently receiving treatment with any agent listed on the prohibited medication list such as valproic acid or other systemic cancer agents
• Any concomitant medical condition that precludes adequate study treatment compliance or assessment, or increases patient risk in the opinion of the investigator:
• 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.
• Uncontrolled heart failure or hypertension, uncontrolled diabetes mellitus, uncontrolled systemic infection,

Sponsors & Collaborators

• Syndax Pharmaceuticals: lead

Study Sites (6)

St. Vincent's University Hospital

Dublin, Ireland

Location

The University of Birmingham

Birmingham, United Kingdom

Location

Velindre Hospital - Whitchurch

Cardiff, United Kingdom

Location

Whiston Hospital; Clatterbridge Centre for Oncology

Liverpool, United Kingdom

Location

University College London Hospitals

London, United Kingdom

Location

Christie Hospital, Manchester Breast Centre

Manchester, United Kingdom

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

entinostat; Aromatase Inhibitors; Therapeutics

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Steroid Synthesis Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Estrogen Antagonists; Hormone Antagonists; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs

Results Point of Contact

• Title: Michael Meyers, MD, PhD, Chief Medical Officer
• Organization: Syndax Pharmaceuticals, Inc.

mmeyers@syndax.com

+1-646-690-7620

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 23, 2009
• First Posted: January 26, 2009
• Study Start: October 1, 2008
• Primary Completion: November 24, 2009
• Study Completion: November 24, 2009
• Last Updated: June 30, 2022
• Results First Posted: June 30, 2022

Record last verified: 2022-06

Locations

IE (1); GB (5)