Clinical Trials Logo

Clinical Trial Summary

Indoleamine 2,3 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 investigator's 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.


Clinical Trial Description

Indoleamine 2,3-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 investigator's 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 investigator's 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-1(PD-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 Design


Related Conditions & MeSH terms


NCT number NCT03896113
Study type Interventional
Source Cliniques universitaires Saint-Luc- Université Catholique de Louvain
Contact Mathieu Luyckx, MD
Phone 27649509
Email mathieu.luyckx@uclouvain.be
Status Recruiting
Phase Phase 2
Start date November 13, 2019
Completion date June 30, 2022

See also
  Status Clinical Trial Phase
Recruiting NCT05036681 - A Phase II Study of Futibatinib and Pembrolizumab in Metastatic Microsatellite Stable Endometrial Carcinoma Phase 2
Completed NCT00377520 - A Trial for Patients With Advanced/Recurrent Endometrial Cancer Phase 2
Recruiting NCT05902988 - A Phase I/II Study of VLS-1488 in Subjects With Advanced Cancer Phase 1/Phase 2
Recruiting NCT06192017 - Development of a Molecular Diagnostic Tool for Endometrial Cancer.
Completed NCT03899441 - Multimedia Aid Gynecologic Counseling and Consent N/A
Completed NCT02552121 - Tisotumab Vedotin (HuMax®-TF-ADC) Safety Study in Patients With Solid Tumors Phase 1/Phase 2
Completed NCT02001623 - Tisotumab Vedotin (HuMax®-TF-ADC) Safety Study in Patients With Solid Tumors Phase 1/Phase 2
Completed NCT02997553 - Fluorescence for Sentinel Lymph Node Identification in Cancer Surgery Phase 3
Suspended NCT03095664 - Effect of a Lifestyle Intervention on Nutritional Status and Prognosis of Endometrial Cancer Survivors N/A
Active, not recruiting NCT01466777 - Endometrial Cancer and Robotic-assisted Versus Traditional Laparoscopy N/A
Completed NCT01068483 - Safety of BKM120 Monotherapy in Advanced Solid Tumor Patients Phase 1
Not yet recruiting NCT03570866 - PET/CT in the Management of Patients With Early Stage Endometrial Cancer
Completed NCT05246462 - The Effect of Logotherapy on Mental Health in Gynecological Cancer Patients N/A
Withdrawn NCT04464967 - Safety and Preliminary Efficacy of SNK01 in Combination With Trastuzumab or Cetuximab in Subjects With Advanced HER2 or EGFR Cancers Phase 1/Phase 2
Recruiting NCT05651282 - Risk Evaluation and Screening to Tailor Prevention and Reduce the Incidence of Endometrial Cancer Phase 4
Completed NCT06187558 - Suspension of the Pelvic and Abdominal Organs During Minimally Invasive Surgery
Completed NCT06312917 - Effect of Physical Activity Intervention on Overweight and Obese Patients With Endometrial Cancer N/A
Active, not recruiting NCT03951415 - Durvalumab and Olaparib in Metastatic or Recurrent Endometrial Cancer Phase 2
Recruiting NCT04212910 - Stratifying Endometrial Cancer Patients Using a PET/MRI Prognostic Model
Completed NCT02221076 - Probe-based and Needle-based Confocal Laser Endomicroscopy During Gynaecological Procedures. N/A