Window of Opportunity Trial of Entinostat in Patients With Newly Diagnosed Stage I-IIIC,TNBC

Breast Cancer Clinical Trial

Official title: A Non-randomized, Non-comparative, Open-label, Window Trial of Entinostat Given With or Without Exemestane in Patients With Newly Diagnosed, Stage I-IIIC, Hormone Receptor - Positive (HR+) or Triple Negative Breast Cancer (TNBC)

Status Terminated

Clinical Trial Summary

This study is investigational and is not designed to treat cancer. In other words, the study drug, entinostat, is not being given to treat cancer. Instead, the study team is looking at the effects of entinostat on tumor tissue for research purposes only.

Approximately 246,660 cases of breast cancer were diagnosed in the United States in 2016. Its detection and treatment remains a major concern in women's healthcare. In particular, TNBC accounts for approximately 15-20% of all breast cancers. Research into treatment for breast cancer relies more and more on understanding how the cancer cells act when they are exposed to an anti-cancer drug. How most cancer cells act when exposed to anti-cancer drugs and which patients as a result may benefit the most from these drugs is not well known. Additional studies are required to determine the cells' reactions. The purpose of part 1 of this study is to better understand how TNBC tumors react to one particular cancer drug, entinostat. Entinostat is currently being studied across multiple clinical trials for the treatment of breast cancer, other solid tumors and blood cancers. Entinostat is investigational and has not yet been FDA approved for the treatment of cancer.

Studies have shown that a good way to determine how cancer acts when exposed to anti-cancer drugs is a short-term preoperative window study. In this type of study, subjects receive a study drug a couple of days before surgery. Leftover tissue from surgery is then used to determine some of the effects that a study drug may have on the tumor. In this study, subjects will receive two doses of entinostat prior to undergoing planned surgery. Leftover tissue from this surgery will then be used to determine the effects entinostat has on tumor cells. For example, the study team will examine if the types of genes and proteins that the tumor expresses as a result of entinostat exposure increases or decreases the likelihood that the tumor will not continue to grow. A gene is a unit of DNA. Genes make up the chemical structure carrying your genetic information that may determine human characteristics (i.e., eye color, height and sex). This study will focus on discovering how entinostat affects a wide variety of genes in tumor cells.

Clinical Trial Description

Primary Objective and Endpoint To identify decrease in Ki-67 mRNA following treatment with entinostat across TNBC breast cancers.

Secondary Objectives and Endpoints To identify messenger ribonucleic acid (mRNA) gene expression changes following treatment with entinostat, across TNBC.

To evaluate changes in the proliferation signature by mRNA expression following treatment with entinostat across TNBC.

To identify differential kinome activation before and after treatment with entinostat across TNBC

To correlate mutation and/or copy number variations by whole exome sequencing (WES) with mRNA gene expression changes and reduction of proliferation signature following treatment with entinostat across TNBC.

To correlate protein lysine hyperacetylation in peripheral blood and tumor from pre- and post-entinostat treated TNBCs.

To explore molecular subtype, Programmed death-ligand 1 (PD-L1) and other immune checkpoint molecule expression, immune gene and innate anti-programed cell death-1 resistance (IPRES) expression signatures and phenotypes of tumor-infiltrating lymphocytes, including delineation of effector and regulatory T cells, and define T cell receptor (TCR) repertoire prior to and following entinostat treatment in TNBCs. We will also explore mutation and copy number variation status, and predicted major histocompatibility complex (MHC) class I neoantigen burden.

To document safety of entinostat in patients with TNBC prior to their scheduled surgical resection per National Cancer Institute - Common Terminology for Adverse Events (NCI-CTCAE v4.0). ;

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms
• ER-Negative PR-Negative HER2-Negative Breast Cancer
• Invasive Breast Cancer
• Triple Negative Breast Neoplasms

• NCT number: NCT03361800
• Study type: Interventional
• Source: UNC Lineberger Comprehensive Cancer Center
• Status: Terminated
• Phase: Early Phase 1
• Start date: November 28, 2018
• Completion date: October 11, 2019