Ignite Creation Date:
2024-05-06 @ 12:56 PM
Last Modification Date:
2024-10-26 @ 1:06 PM
Study NCT ID:
NCT03896113
Status:
UNKNOWN
Last Update Posted:
2020-01-10
First Post:
2019-03-08
Brief Title:
Neoadjuvant Celecoxib in Newly Diagnosed Patients With Endometrial Carcinoma
Sponsor:
Cliniques universitaires Saint-Luc- Université Catholique de Louvain
Organization:
Cliniques universitaires Saint-Luc- Université Catholique de Louvain
Study Overview
Official Title:
Influence of the Celecoxib Administration Before Surgery for Endometrial Cancer on Indoleamine 23-dioxygenase 1 IDO1 Tumor Expression and Immune Cells Tumors Infiltration
Status:
UNKNOWN
Status Verified Date:
2020-01
Last Known Status:
RECRUITING
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
CELEBRIDO
Brief Summary:
Indoleamine 23 dioxygenase 1 IDO 1 is the major enzyme catabolising the Tryptophan outside the liver It has been shown that its plays a important role in generating a immunosuppressive micro-environment in tumors IDO expression has been shown by Hennequart et al to be driven by Cyclooxygenase-2 COX-2 expression The investigators team also shown that anti-COX2 celecoxib can in a xenograft models of ovarian cancer decrease IDO1 expression and result in an infiltration of the tumor by T cells The investigator proposed then to conduct a proof of concept study to evaluate the effect of pre-operative short administration of Celecoxib on IDO expression and Immune cells tumors infiltration in patients with endometrial cancer Indeed this tumor type is well known to express frequently a high level of IDO
Detailed Description:
Indoleamine 23-dioxygenase 1 IDO1 is an enzyme that regulates immune responses by degrading tryptophan which is required for efficient T-cell activation IDO1 expression is limited in normal tissues but is induced by IFN-gamma in inflammatory tissues to prevent excessive T-cell activity The investigators collaborators previously reported that IDO1 is expressed in many human tumours and that pharmacological inhibition of IDO1 leads to immune rejection of IDO1 mouse tumours Based on these results IDO1 inhibitors are now in clinical development A first inhibitor Epacadostat showed encouraging results combined with anti- Programmed Cell Death -1 PD-1 antibodies Tumoural expression of IDO1 can be induced by IFN-gamma which is produced by tumour-infiltrating lymphocytes TIL and represents a mechanism of adaptive immune resistance However other tumours express IDO1 in the absence of TIL and Interferon-gamma INF gamma This seems to be particularly frequent in endometrial carcinoma This constitutive IDO1 expression prevents T-cell infiltration and represents a mechanism of intrinsic immune resistance The investigators collaborators recently showed that constitutive tumoural expression of IDO1 was triggered by cyclooxygenase-2 COX-2 and mediated by autocrine prostaglandin-E2 PGE2 signaling via the Protein Kinase C PKC and phosphoinositide 3-kinase PI3K pathways Constitutive IDO1 expression was reduced by COX-2 inhibitors in vitro Celecoxib is a well-known and widely used anti-inflammatory drug It is a specific inhibitor of COX-2 In vivo celecoxib induced immune rejection of IDO1-expressing human tumour xenografts while reducing IDO1 expression and promoting T-cell infiltration These preclinical results suggest that COX-2 inhibition in patients carrying tumours expressing IDO1 constitutively will decrease IDO1 expression increase T-cell infiltration and might increase responsiveness to anti-PD-1 Programmed Cell Death Ligand-1PD-L1 therapy and thereby exert enhanced anti-tumour activity The investigators wish to obtain clinical evidence that celecoxib can induce these first two effects
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
False
Is an FDA AA801 Violation?:
None