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Expression of IL4 Induced Gene 1 in Patients With Cutaneous Melanoma: Value in Prognosis and/or in Predictive Response to Immune Checkpoint Inhibitors (ENZYMELA)

Primary Purpose

Cutaneous Melanoma

Status

Recruiting

Phase

Not Applicable

Locations

France

Study Type

Interventional

Intervention

Blood sample

Cutaneous melanoma biopsy

About this trial

This is an interventional diagnostic trial for Cutaneous Melanoma focused on measuring cutaneous melanoma, marker for prognosis and response to targeted treatment and/or immune checkpoint inhibitor, Programmed Death ligand 1 (PD1), Cytotoxic T Lymphocyte Associated 4 (CTLA-A4)

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

group 1: patients with primary thin melanoma (Breslow thickness less than or equal to1 mm) monitored for 10 years, having relapsed or not within 10 years after the diagnosis.
- patients with no other concomitant cancers requiring systemic treatment at the time of diagnosis of primary melanoma
- patient or patient's family (in case of death) informed of the objectives and modalities of the study and not opposed to participation in the study
- patient or patient's family (in case of death) not opposed to the use of part of the skin sample previously taken for the present research
group 2: patients with primary thick melanoma (Breslow greater than or equal to 3 mm) monitored for 5 years, having relapsed or not within 5 years after diagnosis.
- patient with no other concomitant cancers requiring systemic treatment at the time of diagnosis of primary melanoma
- patient or patient's family (in case of death) informed of the objectives and modalities of the study and not opposed to participation in the study
- patient or patient's family (in case of death) not opposed to the use of part of the skin sample previously taken for the present research
group 3: patient with melanoma (stages III or IV inoperable) and who are treated with immunotherapy and / or biotherapy
- patient with no other concomitant cancers requiring systemic treatment at the time of diagnosis of primary melanoma and initiation of systemic treatment for melanoma
- patient informed of the objectives and modalities of the study and having given informed and written consent to participate in the study

Exclusion Criteria:

groups 1 and 2: patient or family of the patient opposed (e) that part of the primary melanoma taken previously is used in the context of the present project
group 3 :
- refusal of the patient to participate in the study
- patient unable to understand the study and sign consent
- patient with a known contraindication to xylocaine
- patient not affiliated to a social security system (beneficiary or beneficiary's right)
- adult subject to a legal protection measure

Sites / Locations

Dermatology departmentRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

No Intervention

Other

Arm Label

patients with primary thin melanoma < or = 1mm

patients with primary thick melanoma > or = 3 mm

patient with melanoma who received treatment

Arm Description

patients with primary thin melanoma (Breslow thickness less than or equal 1 mm)

patients with primary thick melanoma (Breslow greater than or equal 3 mm)

patient with melanoma (stages III or IV inoperable) and who received first line treatment with immunotherapy and / or targeted therapies

Outcomes

Primary Outcome Measures

Role of IL4I1+ cells in prognosis and in response to treatments (targeted and/or antiPD1/CTLA4 based therapies) in cutaneous melanoma

Detection of IL4I1+ cells in tissue and/or blood

Secondary Outcome Measures

Full Information

NCT ID

NCT04253080

First Posted

January 31, 2020

Last Updated

October 24, 2022

Sponsor

Assistance Publique - Hôpitaux de Paris

Collaborators

Institut National de la Santé Et de la Recherche Médicale, France, Association Robert Debré (ARD), Société de Dermatologie Française, Institut Cochin

1. Study Identification

Unique Protocol Identification Number

NCT04253080

Brief Title

Expression of IL4 Induced Gene 1 in Patients With Cutaneous Melanoma: Value in Prognosis and/or in Predictive Response to Immune Checkpoint Inhibitors

Acronym

ENZYMELA

Official Title

Impact of the IL4I1 Enzyme Expression in Patients With Cutaneous Melanoma: Prognostic Value and/or Role in Resistance to Current Immunotherapy and Targeted Therapy

Study Type

Interventional

2. Study Status

Record Verification Date

October 2022

Overall Recruitment Status

Recruiting

Study Start Date

April 12, 2022 (Actual)

Primary Completion Date

October 2024 (Anticipated)

Study Completion Date

February 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Assistance Publique - Hôpitaux de Paris

Collaborators

Institut National de la Santé Et de la Recherche Médicale, France, Association Robert Debré (ARD), Société de Dermatologie Française, Institut Cochin

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

Brief Summary

To characterize and quantify immune cells expressing the Interleukine 4 induced gene 1 (IL4I1) immunosuppressive enzyme in the blood and in tissue of melanoma patients (primary tumor, sentinel lymph nodes and cutaneous metastases). Then, to compare the results obtained in different clinical settings: in cases of progression of the disease slower or faster compared to the prognosis established by clinical and pathological data before and after treatments with immunotherapy (anti Programmed Death ligand 1 (anti-PD1) or anti-PD1 and anti Cytotoxic T Lymphocyte associated protein 4 (anti-CTLA-4)) and / or targeted therapies (BRAF inhibitors and /or methyl ethyl ketone (MEK)).

Detailed Description

The incidence of cutaneous melanoma is increasing, but the current prognostic parameters mainly based on histological data are insufficient to identify patients with high risk of recidive. In addition, current immunotherapies using PD-1 and/or CTLA-4 antibodies have long-lasting tumor control in a substantial fraction of patients but identify new markers of treatment resistance need further investigations. Clinical data highlight enzymes involved in amino acid catabolism as new potential prognostic markers in human melanoma. Among those, the IL4I1 phenylalanine oxidase may be a new relevant marker and may represent an easily targetable molecule for cancer immunotherapy. The current retrospective study is designed to evaluate whether a high proportion of IL4I1 positive cells within the primary tumor and/or sentinel lymph nodes allows to predict the risk of cancer recurrence from the clinical diagnosis. Immunofluorescence and immunohistochemistry will be performed. The longitudinal study of IL4I1 positive cells in the blood and cutaneous metastasis od patients will start before and after (three months and 1 year (or before in case of treatment resistance) the treatment with targeted therapy and/or immunotherapy as a first line. Treatment will be administered on an outpatient basis. No investigational or commercial cancer directed agents or therapies other than those described below may be administered. It is designed to evaluate whether patients that resist to treatments exhibit a high proportion of IL4I1 positive cells and how is regulated the enzyme in the course of the treatment.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Cutaneous Melanoma

Keywords

cutaneous melanoma, marker for prognosis and response to targeted treatment and/or immune checkpoint inhibitor, Programmed Death ligand 1 (PD1), Cytotoxic T Lymphocyte Associated 4 (CTLA-A4)

7. Study Design

Primary Purpose

Diagnostic

Study Phase

Not Applicable

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

170 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

patients with primary thin melanoma < or = 1mm

Arm Type

No Intervention

Arm Description

patients with primary thin melanoma (Breslow thickness less than or equal 1 mm)

Arm Title

patients with primary thick melanoma > or = 3 mm

Arm Type

No Intervention

Arm Description

patients with primary thick melanoma (Breslow greater than or equal 3 mm)

Arm Title

patient with melanoma who received treatment

Arm Type

Other

Arm Description

patient with melanoma (stages III or IV inoperable) and who received first line treatment with immunotherapy and / or targeted therapies

Intervention Type

Biological

Intervention Name(s)

Blood sample

Intervention Description

Blood sample before treatment, 3 months after treatment and after 1 year or relapse or resumption of disease progression.

Intervention Type

Biological

Intervention Name(s)

Cutaneous melanoma biopsy

Intervention Description

Cutaneous melanoma biopsy before treatment, 3 months after treatment and relapse or resumption of disease progression.

Primary Outcome Measure Information:

Title

Role of IL4I1+ cells in prognosis and in response to treatments (targeted and/or antiPD1/CTLA4 based therapies) in cutaneous melanoma

Description

Detection of IL4I1+ cells in tissue and/or blood

Time Frame

12 months or between 6 and 12 months (if disease progression)

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: group 1: patients with primary thin melanoma (Breslow thickness less than or equal to1 mm) monitored for 10 years, having relapsed or not within 10 years after the diagnosis. patients with no other concomitant cancers requiring systemic treatment at the time of diagnosis of primary melanoma patient or patient's family (in case of death) informed of the objectives and modalities of the study and not opposed to participation in the study patient or patient's family (in case of death) not opposed to the use of part of the skin sample previously taken for the present research group 2: patients with primary thick melanoma (Breslow greater than or equal to 3 mm) monitored for 5 years, having relapsed or not within 5 years after diagnosis. patient with no other concomitant cancers requiring systemic treatment at the time of diagnosis of primary melanoma patient or patient's family (in case of death) informed of the objectives and modalities of the study and not opposed to participation in the study patient or patient's family (in case of death) not opposed to the use of part of the skin sample previously taken for the present research group 3: patient with melanoma (stages III or IV inoperable) and who are treated with immunotherapy and / or biotherapy patient with no other concomitant cancers requiring systemic treatment at the time of diagnosis of primary melanoma and initiation of systemic treatment for melanoma patient informed of the objectives and modalities of the study and having given informed and written consent to participate in the study Exclusion Criteria: groups 1 and 2: patient or family of the patient opposed (e) that part of the primary melanoma taken previously is used in the context of the present project group 3 : refusal of the patient to participate in the study patient unable to understand the study and sign consent patient with a known contraindication to xylocaine patient not affiliated to a social security system (beneficiary or beneficiary's right) adult subject to a legal protection measure

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Nora Kramkimel, MD, PhD

Phone

+33 1 58 41 19 80

nora.kramkimel@aphp.fr

First Name & Middle Initial & Last Name or Official Title & Degree

Christelle Auger

Phone

+33 1 58 41 11 86

christelle.auger@aphp.fr

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Armelle Blondel, MD, PhD

Organizational Affiliation

Institut National de la Santé Et de la Recherche Médicale, France

Official's Role

Principal Investigator

Facility Information:

Facility Name

Dermatology department

City

Paris

State/Province

Ile De France

ZIP/Postal Code

75014

Country

France

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Nora Kramkimel, MD, PhD

Phone

+33 1 58 41 19 80

nora.kramkimel@aphp.fr

First Name & Middle Initial & Last Name & Degree

Nora Kramkimel, MD, PhD

First Name & Middle Initial & Last Name & Degree

Eve Maubec, Professor, MD, PhD

12. IPD Sharing Statement

Plan to Share IPD

IPD Sharing Plan Description

The clinical data at the diagnosis and the relapse/no relapse information have to be shared from the groups 1 and 2. The clinical response to treatments will be shared.

Citations:

PubMed Identifier

30048651

Citation

Ramspott JP, Bekkat F, Bod L, Favier M, Terris B, Salomon A, Djerroudi L, Zaenker KS, Richard Y, Molinier-Frenkel V, Castellano F, Avril MF, Prevost-Blondel A. Emerging Role of IL-4-Induced Gene 1 as a Prognostic Biomarker Affecting the Local T-Cell Response in Human Cutaneous Melanoma. J Invest Dermatol. 2018 Dec;138(12):2625-2634. doi: 10.1016/j.jid.2018.06.178. Epub 2018 Jul 23.

Results Reference

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PubMed Identifier

28405502

Citation

Bod L, Lengagne R, Wrobel L, Ramspott JP, Kato M, Avril MF, Castellano F, Molinier-Frenkel V, Prevost-Blondel A. IL4-induced gene 1 promotes tumor growth by shaping the immune microenvironment in melanoma. Oncoimmunology. 2017 Jan 13;6(3):e1278331. doi: 10.1080/2162402X.2016.1278331. eCollection 2017.

Results Reference

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Expression of IL4 Induced Gene 1 in Patients With Cutaneous Melanoma: Value in Prognosis and/or in Predictive Response to Immune Checkpoint Inhibitors

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