Ignite Creation Date:
2024-05-06 @ 10:49 AM
Last Modification Date:
2024-10-26 @ 12:36 PM
Study NCT ID:
NCT03361800
Status:
TERMINATED
Last Update Posted:
2024-03-25
First Post:
2017-11-28
Brief Title:
Window of Opportunity Trial of Entinostat in Patients With Newly Diagnosed Stage I-IIICTNBC
Sponsor:
UNC Lineberger Comprehensive Cancer Center
Organization:
UNC Lineberger Comprehensive Cancer Center
Study Overview
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
Status Verified Date:
2024-03
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Funding withdrawn
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief 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 246660 cases of breast cancer were diagnosed in the United States in 2016 Its detection and treatment remains a major concern in womens 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 ie eye color height and sex This study will focus on discovering how entinostat affects a wide variety of genes in tumor cells
Approximately 246660 cases of breast cancer were diagnosed in the United States in 2016 Its detection and treatment remains a major concern in womens 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 ie eye color height and sex This study will focus on discovering how entinostat affects a wide variety of genes in tumor cells
Detailed 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 andor 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 v40
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 andor 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 v40
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| P50CA058223 | NIH | None | httpsreporternihgovquickSearchP50CA058223 |