Metastatic Melanoma
Conditions
Keywords
Melanoma, Anti-PD1 monoclonal antibodies, Immune modulation, BRAF
Brief summary
This is an open mono-centric prospective non-randomized study in patients with metastatic melanoma treated with Anti-PD1 monoclonal antibodies (Nivolumab). The aim of the study is to identify the immune cells modulations differences between patients who present a complete, partial or stable response and patients who have non-response to the therapy in order to establish an improving response rate strategy.
Interventions
BIOLOGICALblood sampling
Blood samples (44mL) will be taken before starting treatment with Nivolumab and at week 2, week 12, week 54 or at relapse (before week 54)
DRUGNivolumab
injection of Nivolumab every two weeks from day 0 and until relapse, toxicity motivating withdrawal or temporary suspension of treatment or up to 54 weeks.
Sponsors
Hospices Civils de Lyon
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Men and women aged ≥ 18 years * Patient with metastatic or unresectable melanoma * Anti-PD1 monoclonal antibodies treatment indication * Patient affiliated to a social security regime * Signed Written Informed Consent. * agree with the storage of his biological samples * Women of childbearing potential must as mentioned in the summary of product characteristics (SPC) using two effective methods of contraception during treatment, and men whose partner is of childbearing potential must use effective contraception during treatment. For all patients treated men and women, contraception should be continued during the four months following the discontinuation of nivolumab.
Exclusion criteria
* development of haematological tumor during treatment * Patients requiring concomitant chronic treatment with systemic corticosteroids or other immunosuppressive agents * Patients with autoimmune disease. * Patient with Occular melanoma
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| change the percentage of cells producing cytokines in monocytes before treatment and on treatment | before treatment (week 0), at week 2, at week 12, at week 54 or at relapse (before 54 weeks) | % of cells producing cytokines in monocytes |
| change the absolute number of dendritic cells before treatment and on treatment | before treatment (week 0), at week 2, at week 12, at week 54 or at relapse (before 54 weeks) | absolute number / mm 3 of dendritic cells |
| change the percentage of cells producing cytokines in dendritic cells before treatment and on treatment | before treatment (week 0), at week 2, at week 12, at week 54 or at relapse (before 54 weeks) | % of cells producing cytokines in dendritic cells |
| change the absolute number of subpopulations of T lymphocytes before treatment and on treatment | before treatment (week 0), at week 2, at week 12, at week 54 or at relapse (before 54 weeks) | absolute number / mm 3 of different subpopulations of T lymphocyte |
| change the absolute number of monocytes before treatment and on treatment | before treatment (week 0), at week 2, at week 12, at week 54 or at relapse (before 54 weeks) | absolute number / mm 3 of monocytes |
| change the percentage of cells producing cytokines in subpopulations of T lymphocytes before treatment and on treatment | before treatment (week 0), at week 2, at week 12, at week 54 or at relapse (before 54 weeks) | % of cells producing cytokines in subpopulations of T lymphocytes |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| correlation between biological parameters on overall survival | death between the date of first injection of immunotherapy and week 54 | absolute number / mm 3 of different population of cells and % of cells producing cytokines in the different population of cells will be correlated with the overall survival |
| Identify predictive factors of overall response rate at week 12 based on RECIST and ir-RECIST criteria | response evaluation at week 12 | predictive factors like histological and cytological initial tumor type, initial immunological status will be evaluated at inclusion and correlated with the response |
| impact of treatments received prior to inclusion in the study on the biological parameters before and on treatment | antitumor treatment received from diagnosis of melanoma to inclusion | absolute number / mm 3 of different population of cells and % of cells producing cytokines in the different population of cells will be correlated with treatments received prior to inclusion |
| correlation between the occurrence of autoimmune side effects and the biological parameters before and on treatment | occurence of autoimmune side effects from day 0 to week 54 | absolute number / mm 3 of different population of cells and % of cells producing cytokines in the different population of cells will be correlated with autoimmune side effects, based on CTCAE classification |
| correlation between biological parameters and progression-free survival | progression between the date of first injection of immunotherapy and week 54 based on RECIST and ir-RECIST criterion | absolute number / mm 3 of different population of cells and % of cells producing cytokines in the different population of cells will be correlated with the progression free survival |
Countries
France
Outcome results
None listed