Ignite Creation Date:
2024-10-26 @ 3:41 PM
Last Modification Date:
2024-10-26 @ 3:41 PM
Study NCT ID:
NCT06611072
Status:
NOT_YET_RECRUITING
Last Update Posted:
None
First Post:
2024-08-04
Brief Title:
ACTivating the Immune Response in Ovarian CaNcer
Sponsor:
None
Organization:
None
Study Overview
Official Title:
Activating the Immune Response in Ovarian Cancer ACTION Study
Status:
NOT_YET_RECRUITING
Status Verified Date:
2024-09
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
No
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
ACTION
Brief Summary:
The goal of this multi-center explorative cross-sectional study is to characterize and phenotype the immune state of ovarian cancer OC patients compared to controls without cancer thereby focusing on the hematopoietic organs and the immune cells originating from these organs This will be executed by assessing the transcriptional epigenetic and functional programming of circulating monocytes and myeloid progenitor cells in OC
It is hypothesized that OC and its progression are heavily influenced by myeloid cells and their progenitors mainly through defective trained immunity responses It is hypothesized that OC patients suffer from a suppressive trained immunity phenotype
Researchers will compare 1 patients with OC who undergo primary debulking surgery and 2 patients with OC who undergo interval debulking surgery to 3 controls as blood and bone marrow donors to see if there are differences between the transcriptional epigenetic and functional signature of i circulating and intra-abdominal monocytes and ii bone marrow and spleen myeloid progenitor cells
Participants will get a
Vena puncture
Bone marrow aspiration
Tumor biopsy only cases
Spleen biopsy only cases
Furthermore peritoneal fluid will be sent for analysis in all patients
It is hypothesized that OC and its progression are heavily influenced by myeloid cells and their progenitors mainly through defective trained immunity responses It is hypothesized that OC patients suffer from a suppressive trained immunity phenotype
Researchers will compare 1 patients with OC who undergo primary debulking surgery and 2 patients with OC who undergo interval debulking surgery to 3 controls as blood and bone marrow donors to see if there are differences between the transcriptional epigenetic and functional signature of i circulating and intra-abdominal monocytes and ii bone marrow and spleen myeloid progenitor cells
Participants will get a
Vena puncture
Bone marrow aspiration
Tumor biopsy only cases
Spleen biopsy only cases
Furthermore peritoneal fluid will be sent for analysis in all patients
Detailed Description:
DESCRIPTION OF THE PROBLEM
Ovarian cancer OC is one of the most lethal cancers due to late-stage of disease at diagnosis Standard therapy consists of debulking surgery and chemotherapy However despite this aggressive treatment recurrent disease almost invariably occurs resulting in a five-year survival rate of approximately 30 Immunotherapy could be a way to increase survival in OC patients However a major barrier to a successful deployment of cancer immunotherapy for ovarian cancer patients is the immunosuppressive tumor microenvironment
RESEARCH DIRECTION
Tumor-related inflammation is one of the hallmarks of cancers in general Innate immunity specifically is a common denominator that is involved in the pathogenesis of OC To improve the patients outcome and identify novel therapeutic targets one needs a deeper understanding of the tumor-induced changes in the bone marrow myeloid progenitor cells
HYPOTHESIS
It is hypothesized that OC and its progression are heavily influenced by myeloid cells and their progenitors mainly through defective trained immunity responses It is hypothesized that OC patients suffer from a suppressive trained immunity phenotype In the future therapeutic targeting of trained immunity could be explored to develop novel immunotherapies for tumors that are refractory to conventional treatment
OBJECTIVE
To characterize and phenotype the immune state of OC patients compared to controls without cancer thereby focusing on the hematopoietic organs and the immune cells originating from these organs
This will be executed by assessing the transcriptional epigenetic and functional programming of circulating monocytes and myeloid progenitor cells in OC
STUDY DESIGN
Investigator-initiated multi-center explorative cross-sectional study at the Catharina hospital Eindhoven Radboud University Medical Center and Eindhoven University of Technology
STUDY POPULATION
The following patients will be included in the study
Group 1 Patients with OC who undergo primary debulking surgery N30
Group 2 Patients with OC who undergo interval debulking surgery N30
Group 3 Controls as blood and bone marrow donors N30
MAIN STUDY PARAMETERSENDPOINTS
Primary endpoints transcriptional epigenetic and functional signature of circulating monocytes and myeloid progenitors For transcriptional markers differentially expressed genes between the different groups will be the focus with a particular emphasis on antigen presentation and processing pathways inflammatory pathways eg NF-kB metabolic pathways and enzymes and pattern-recognition receptor PRR signal transduction For epigenetic markers the focus will be on three histone marks positively associated with gene expression and trained immunity H3K4me3 which marks promoters H3K4me1 which marks distal regulatory elements enhancers and H3K27ac which marks active promoters and enhancers For functional markers the focus will be on the degree of trained immunity response in vitro
Ovarian cancer OC is one of the most lethal cancers due to late-stage of disease at diagnosis Standard therapy consists of debulking surgery and chemotherapy However despite this aggressive treatment recurrent disease almost invariably occurs resulting in a five-year survival rate of approximately 30 Immunotherapy could be a way to increase survival in OC patients However a major barrier to a successful deployment of cancer immunotherapy for ovarian cancer patients is the immunosuppressive tumor microenvironment
RESEARCH DIRECTION
Tumor-related inflammation is one of the hallmarks of cancers in general Innate immunity specifically is a common denominator that is involved in the pathogenesis of OC To improve the patients outcome and identify novel therapeutic targets one needs a deeper understanding of the tumor-induced changes in the bone marrow myeloid progenitor cells
HYPOTHESIS
It is hypothesized that OC and its progression are heavily influenced by myeloid cells and their progenitors mainly through defective trained immunity responses It is hypothesized that OC patients suffer from a suppressive trained immunity phenotype In the future therapeutic targeting of trained immunity could be explored to develop novel immunotherapies for tumors that are refractory to conventional treatment
OBJECTIVE
To characterize and phenotype the immune state of OC patients compared to controls without cancer thereby focusing on the hematopoietic organs and the immune cells originating from these organs
This will be executed by assessing the transcriptional epigenetic and functional programming of circulating monocytes and myeloid progenitor cells in OC
STUDY DESIGN
Investigator-initiated multi-center explorative cross-sectional study at the Catharina hospital Eindhoven Radboud University Medical Center and Eindhoven University of Technology
STUDY POPULATION
The following patients will be included in the study
Group 1 Patients with OC who undergo primary debulking surgery N30
Group 2 Patients with OC who undergo interval debulking surgery N30
Group 3 Controls as blood and bone marrow donors N30
MAIN STUDY PARAMETERSENDPOINTS
Primary endpoints transcriptional epigenetic and functional signature of circulating monocytes and myeloid progenitors For transcriptional markers differentially expressed genes between the different groups will be the focus with a particular emphasis on antigen presentation and processing pathways inflammatory pathways eg NF-kB metabolic pathways and enzymes and pattern-recognition receptor PRR signal transduction For epigenetic markers the focus will be on three histone marks positively associated with gene expression and trained immunity H3K4me3 which marks promoters H3K4me1 which marks distal regulatory elements enhancers and H3K27ac which marks active promoters and enhancers For functional markers the focus will be on the degree of trained immunity response in vitro
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None