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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)

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ClinicalTrials.gov Identifier: NCT04253080
Recruitment Status : Not yet recruiting
First Posted : February 5, 2020
Last Update Posted : February 5, 2020
Sponsor:
Collaborators:
Institut National de la Santé Et de la Recherche Médicale, France
Association Robert Debré (ARD)
Société de Dermatologie Française
Institut Cochin
Information provided by (Responsible Party):
Assistance Publique - Hôpitaux de Paris

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)).

Condition or disease Intervention/treatment Phase
Cutaneous Melanoma Biological: Blood sample Biological: Cutaneous melanoma biopsy Not Applicable

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 170 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Diagnostic
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
Estimated Study Start Date : March 2020
Estimated Primary Completion Date : September 2022
Estimated Study Completion Date : March 2023

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Melanoma

Arm Intervention/treatment
No Intervention: patients with primary thin melanoma < 1mm
patients with primary thin melanoma (Breslow thickness less than 1 mm)
No Intervention: patients with primary thick melanoma > 3 mm
patients with primary thick melanoma (Breslow greater than 3 mm)
patient with melanoma who received first line treatment
patient with melanoma (stages III or IV inoperable) and who received first line treatment with immunotherapy and / or targeted therapies
Biological: Blood sample
Blood sample before treatment, 3 months after treatment and after 1 year or relapse or resumption of disease progression.

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




Primary Outcome Measures :
  1. Role of IL4I1+ cells in prognosis and in response to treatments (targeted and/or antiPD1/CTLA4 based therapies) in cutaneous melanoma [ Time Frame: 12 months or between 6 and 12 months (if disease progression) ]
    Detection of IL4I1+ cells in tissue and/or blood



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • group 1: patients with primary thin melanoma (Breslow thickness less than 1 mm) monitored for 10 years, having relapsed or not within 10 years after the diagnosis.

patients with no other concomitant cancers.

- group 2: patients with primary thick melanoma (Breslow greater than 3 mm) monitored for 5 years, having relapsed or not within 5 years after diagnosis.

patient with no other concomitant cancers

The selection of the patients will be done according to a pairing: a patient having presented a first relapse will be matched to a patient without relapse the latter having the following criteria:

  • diagnosis at the same time (in the year)
  • Age equivalent (+/- 3 years)
  • if possible same sex
  • similar Breslow thickness (for fine melanoma in quartile 0.25 mm, for thick melanoma thickness in mm)

    • Group 3:

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

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 who has already received a first-line treatment
  • patient already participating in another protocol

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04253080


Contacts
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Contact: Nora Kramkimel, MD, PhD +33 1 58 41 19 80 nora.kramkimel@aphp.fr
Contact: Christelle Auger +33 1 58 41 11 86 christelle.auger@aphp.fr

Locations
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France
Dermatology department
Paris, Ile De France, France, 75014
Contact: Nora Kramkimel, MD, PhD    +33 1 58 41 19 80    nora.kramkimel@aphp.fr   
Principal Investigator: Nora Kramkimel, MD, PhD         
Sub-Investigator: Eve Maubec, Professor, MD, PhD         
Sponsors and Collaborators
Assistance Publique - Hôpitaux de Paris
Institut National de la Santé Et de la Recherche Médicale, France
Association Robert Debré (ARD)
Société de Dermatologie Française
Institut Cochin
Investigators
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Principal Investigator: Armelle Blondel, MD, PhD Institut National de la Santé Et de la Recherche Médicale, France
Publications:
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Responsible Party: Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier: NCT04253080    
Other Study ID Numbers: APHP190243
2019-A01985-52 ( Registry Identifier: ID-RCB )
First Posted: February 5, 2020    Key Record Dates
Last Update Posted: February 5, 2020
Last Verified: January 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
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.


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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Assistance Publique - Hôpitaux de Paris:
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)
Additional relevant MeSH terms:
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Melanoma
Skin Neoplasms
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas
Neoplasms by Site
Skin Diseases