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
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|
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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||170 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|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|
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.
- 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
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04253080
|Contact: Nora Kramkimel, MD, PhD||+33 1 58 41 19 email@example.com|
|Contact: Christelle Auger||+33 1 58 41 11 firstname.lastname@example.org|
|Paris, Ile De France, France, 75014|
|Contact: Nora Kramkimel, MD, PhD +33 1 58 41 19 80 email@example.com|
|Principal Investigator: Nora Kramkimel, MD, PhD|
|Sub-Investigator: Eve Maubec, Professor, MD, PhD|
|Principal Investigator:||Armelle Blondel, MD, PhD||Institut National de la Santé Et de la Recherche Médicale, France|