Neoadjuvant Celecoxib in Newly Diagnosed Patients With Endometrial Carcinoma

NCT03896113 | Unknown Phase 2

• 1 other identifier: LUC19-001
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 2

Brief 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.

Conditions

Endometrium Cancer

Outcome Measures

Primary Outcomes (2)

• 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.

  after 15 days of celecoxib administration

• 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

  after 15 days of celecoxib administration

Secondary Outcomes (1)

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

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

Study Arms (1)

Celecoxib

EXPERIMENTAL

Patients 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.

Drug: Celecoxib 200mg capsule

Interventions

Celecoxib 200mg capsule DRUG

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

Also known as: Cyclooxygenase-2 (COX-2) inhibitor

Celecoxib

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Cliniques universitaires Saint-Luc- Université Catholique de Louvain: lead

Study Sites (2)

Cliniques Universitaires Saint Luc

Brussels, 1200, Belgium

RECRUITING

Gasthuisberg - KULeuven

Leuven, 3000, Belgium

NOT YET RECRUITING

Related Publications (1)

• 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.

  PMID: 28765120 BACKGROUND

MeSH Terms

Conditions

Endometrial Neoplasms

Interventions

Celecoxib; Cyclooxygenase 2

Condition Hierarchy (Ancestors)

Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases

Intervention Hierarchy (Ancestors)

Benzenesulfonamides; Sulfonamides; Amides; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Sulfones; Sulfur Compounds; Pyrazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Prostaglandin-Endoperoxide Synthases; Multienzyme Complexes; Enzymes; Enzymes and Coenzymes

Study Officials

• Benoit van den Eynde, PhD

  Institut de Duve - UCL

  STUDY DIRECTOR

• Nicolas Van Baeren, PhD

  Institut de Duve- UCL

  STUDY DIRECTOR

• Jean-François Baurain, PhD

  Cliniques universitaire St-Luc

  STUDY CHAIR

• Pierre van der Bruggen, PhD

  Institut de Duve

  STUDY CHAIR

Central Study Contacts

Mathieu Luyckx, MD

CONTACT

27649509; mathieu.luyckx@uclouvain.be

Jean-Luc Squifflet, PhD

CONTACT

27641071; jean-luc.squifflet@uclouvain.be

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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

Study Record Dates

• First Submitted: March 8, 2019
• First Posted: March 29, 2019
• Study Start: November 13, 2019
• Primary Completion: June 30, 2022
• Study Completion: June 30, 2022
• Last Updated: January 10, 2020

Record last verified: 2020-01

Data Sharing

• IPD Sharing: Will not share

Locations

BE (2)