AzTrials
AzTrials

Endometrium CancerPhase 2CELEBRIDONCT03896113

Neoadjuvant Celecoxib in Newly Diagnosed Patients With Endometrial Carcinoma

A Phase 2 study testing Celecoxib 200mg capsule in people with Endometrium Cancer, run by Cliniques universitaires Saint-Luc- Université Catholique de Louvain at 2 sites in Belgium.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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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. Read more about this study

Who is it for?
Ages 18 to 99 years, women only
Conditions the study is for
Endometrium Cancer
What is being tested?
Celecoxib 200mg capsule
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
48 participants
Where
2 sitesBelgium
Study dates
13 Nov 2019to 30 Jun 2022
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 99 years
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Women > 18 years of age.
  • Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2
  • Adequate renal, hepatic and haematologic functions as defined by laboratory parameters.
  • Agrees to undergo additional endometrial biopsies for scientific purposes.

Who cannot join

  • Known hypersensitivity or intolerance to celecoxib
  • Active, known or suspected autoimmune disease. Vitiligo, type I diabetes mellitus, residual hypothyroidism controlled by hormone substitution therapy, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are allowed.
  • Positive hepatitis B or C, HIV, and pregnancy tests.
  • Immunosuppressive treatment

Trial locations and contacts

2 sites in 1 country.

Mathieu Luyckx, MD contact

27649509 ext. +32

mathieu.luyckx@uclouvain.be

Jean-Luc Squifflet, PhD contact

27641071 ext. +32

jean-luc.squifflet@uclouvain.be

Belgium2 sites, 2 recruiting

  • Cliniques Universitaires Saint Luc

    Brussels, 1200

    Mathieu Luyckx, MD, +3227649509, mathieu.luyckx@uclouvain.be

    Mathieu Luyckx, MD

    Recruiting

  • Gasthuisberg - KULeuven

    Leuven, 3000

    Ignace Vergote, PhD, 16 3 44635 ext. + 32, ignace.vergote@kuleuven.be

    An Coosemans, PhD, 16 3 44635 ext. +32, an.coosemans@kuleuven.be

    Not yet recruiting

Other trials in Belgium

About this study

Official title: Influence of the Celecoxib Administration Before Surgery for Endometrial Cancer on Indoleamine 2,3-dioxygenase 1 (IDO1) Tumor Expression and Immune Cells Tumor's Infiltration

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.

Read the detailed 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

Being tested
Celecoxib 200mg capsule
Medical subject headings
Endometrial Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Celecoxib 200mg capsuleDrug

    Also called Cyclooxygenase-2 (COX-2) inhibitor

    Patient confirmed with endometrial cancer will received twice daily 200 mg Celecoxib, 15 days before the surgery.

Study groups in NCT03896113
Study groupRoleWhat they receive
CelecoxibExperimentalPatients with confirmed primary endometrioid adenocarcinoma eligible for first line curative surgery will receive celecoxib 400 mg twice a day, for 15 days before the curative surgery for their endometrial cancer. The patients will undergo an endometrial biopsy at the inclusion and during the surgery.
Receives: Drug: Celecoxib 200mg capsule

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Reduction of tumoural cells expression IDO after celecoxib treatment. If more than 10% of all the tumoural cells have a staining for IDO, the tumour is considered as IDO (+), if less than 10%.

    Reduction of Tumoral IDO expression after Celecoxib treatment by immunohistochemistry, digital identification of the cells and phenotype and computer count of IDO positive cells inside de tumour (then total number compared before and after the treatment). If more than 10% of all the tumoural cells have a staining for IDO, the tumour is considered as IDO (+), if less than 10%, it is considered as (-).

    Based on animal models, the treatment with celecoxib should decreases IDO expression in tumoural cells, allowing an immune cells tumoural's infiltration.

    Measured: after 15 days of celecoxib administration

  2. Modification of tumoural T Cells infiltration after the treatment with celecoxib. The number of Cluster of Differenciation (CD) 4 and CD8 T cells will be counted before and after the treatment.

    Observed the modification of the T cell tumoral's infiltration after the celecoxib treatment by immunohistochemistry, digital identification of the cells and phenotype and computer count of the different T cells population inside de tumour (then total number compared before and after the treatment). The number of CD4 and CD8 T cells will be counted before and after the treatment and the median of all the sample before and after the treatment will be compared to assess if there is a significant difference of total number of T cells before and after the treatment. Unit= nombre of CD4 and CD8 T Cells. Based on animal model, the investigators expect to have a significant increase of T cells infiltration after the celecoxib treatment

    Measured: after 15 days of celecoxib administration

Secondary outcomes (1)

  1. Number of participants with treatment-related adverse events as assessed by Common Terminology Criteria for Adverse Event Version 4.0 (CTCAE v4.0).

    Assessment and scaling of adverse events according to CTCAE v4.0, Grade 1 Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2 Moderate; minimal, local or noninvasive intervention indicated;

    Grade 3 Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care Grade 4 Life-threatening consequences; urgent intervention indicated. Grade 5 Death related to Adverse Event.

    Measured: from the first intake of the celecoxib to one day after the surgery

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted29 Mar 2019
  2. Study start13 Nov 2019
  3. Primary completion30 Jun 2022 (estimated)
  4. Study completion30 Jun 2022 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Model description
Open label, proof of concept phase II study. One arm, no placebo: All the patient will received the treatment and biopsies before and after the treatment will be compared regarding Indoleamine 2,3-dioxygenase 1 (IDO-1) expression and Immune T cells infiltration of the tumour
Masking
None (open label)
Enrolment
48 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03896113
Sponsor's protocol ID
LUC19-001
Acronym
CELEBRIDO
Status last verified
Jan 2020
First submitted
8 Mar 2019
Last updated
10 Jan 2020
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Hennequart M, Pilotte L, Cane S, Hoffmann D, Stroobant V, Plaen E, Van den Eynde BJ. Constitutive IDO1 Expression in Human Tumors Is Driven by Cyclooxygenase-2 and Mediates Intrinsic Immune Resistance. Cancer Immunol Res. 2017 Aug;5(8):695-709. doi: 10.1158/2326-6066.CIR-16-0400. Epub 2017 Jul 21.

    PubMed 28765120

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Celecoxib 200mg capsule in people with Endometrium Cancer, run by Cliniques universitaires Saint-Luc- Université Catholique de Louvain at 2 sites in Belgium.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 10 Jan 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in Belgium. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

Contact Mathieu Luyckx, MD (27649509 ext. +32, mathieu.luyckx@uclouvain.be), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Reduction of tumoural cells expression IDO after celecoxib treatment. If more than 10% of all the tumoural cells have a staining for IDO, the tumour is considered as IDO (+), if less than 10%. (time frame: after 15 days of celecoxib administration). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03896113, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Jan 2020.

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