Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Breast Neoplasms

Breast Diseases

Skin Diseases

All Drugs and Chemicals

Antineoplastic Agents

Hormones

Fulvestrant

Estrogens

Selective Estrogen Receptor Modulators

Estrogen Receptor Modulators

Entinostat

Histone Deacetylase Inhibitors

Antineoplastic Agents, Hormonal

Estrogen Antagonists

Estrogen Receptor Antagonists

Hormone Antagonists

Enzyme Inhibitors

Arm A: Fulvestrant (500 mg on C1D1, C1D15, C2D1, and on Day 1 of each subsequent cycle) plus entinostat (5 mg PO once weekly)

Arm B: Fulvestrant (500 mg on C1D1, C1D15, C2D1, and on Day 1 of each subsequent cycle) plus placebo (5 mg PO once weekly)

Placebo

Denise Yardley, MD

Preclinical data has demonstrated that entinostat (SNDX-275) can enhance fulvestrant sensitivity in hormone receptor-positive breast cancer in animal models. The addition of entinostat to fulvestrant will provide clinical benefit to patients with locally advanced or metastatic breast when compared to fulvestrant plus placebo. Also, based on previous data, patients exposed to entinostat who demonstrate an elevated level of protein lysine acetylation will have an improved efficacy outcome.

Entinostat (SNDX-275) inhibits mechanisms of resistance to hormone therapy in breast cancer (BC) cells, thereby prolonging sensitivity of the cells to fulvestrant. Preclinical data has demonstrated that entinostat can enhance fulvestrant sensitivity in hormone receptor-positive BC in animal models. Thus, it is hypothesized that the addition of entinostat to fulvestrant will provide clinical benefit to patients with locally advanced or metastatic BC when compared to fulvestrant plus placebo.

Preliminary data from Phase 2 Study SNDX-275-0301 suggest patients with higher levels of protein lysine acetylation who receive entinostat with exemestane potentially have improved clinical outcomes (e.g., PFS, OS) when compared to patients with lower levels of protein lysine acetylation. Thus, it is hypothesized that patients exposed to entinostat and who demonstrate an elevated level of protein lysine acetylation will have an improved efficacy outcome.

Phase 2 Study of Fulvestrant With and Without Entinostat in Postmenopausal Women With ER+ Advanced Breast Cancer

A Phase 2, Randomized, Double-Blind, Multicenter Study of Fulvestrant With and Without Entinostat in Postmenopausal Women With Hormone Receptor-Positive Advanced Breast Cancer

molecular classification of breast cancer (BC) subtypes, DNA methylation, e-cadherin levels, protein lysine acetylation levels, and changes in proteins associated with estrogen signaling and fulvestrant resistance

Syndax Pharmaceuticals

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Phase 2 Study of Fulvestrant With and Without Entinostat in Postmenopausal Women With ER+ Advanced Breast Cancer	NCT02115594	Breast Cancer	Fulvestrant Entinostat Placebo	-	Syndax Pharmaceuticals
Phase 2 Study of Fulvestrant With and Without Entinostat in Postmenopausal Women With ER+ Advanced Breast Cancer	NCT02115594	Breast Cancer	Fulvestrant Entinostat Placebo	-	Syndax Pharmaceuticals

Spots Global Cancer Trial Database for estrogen receptor modulators, selective