Immune Modulation Study in Patients With Metastatic Melanoma Treated With Anti-PD1 Monoclonal Antibodies (PAIR)

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.

Study Overview

• Status: Unknown
• Conditions: Metastatic Melanoma
• Intervention / Treatment: Biological: blood sampling; Drug: Nivolumab

• Study Type: Interventional
• Enrollment (Actual): 32
• Phase: Phase 4

Contacts and Locations

Study Locations

• France
  • Pierre Benite, France, 69310
    • Centre Hospitalier Lyon Sud

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Nivolumab, patients with BRAF mutation; Nivolumab (dose equal to 3mg/kg), 10 mg/ml solution for infusion. 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. Blood sampling at different time	Biological: blood 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); Drug: Nivolumab; 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.
Experimental: Nivolumab, patients with BRAF wild type; Nivolumab (dose equal to 3mg/kg), 10 mg/ml solution for infusion. 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. Blood sampling at different time	Biological: blood 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); Drug: Nivolumab; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
change the absolute number of dendritic cells before treatment and on treatment	absolute number / mm 3 of dendritic cells	before treatment (week 0), at week 2, at week 12, at week 54 or at relapse (before 54 weeks)
change the percentage of cells producing cytokines in dendritic cells before treatment and on treatment	% of cells producing cytokines in dendritic cells	before treatment (week 0), at week 2, at week 12, at week 54 or at relapse (before 54 weeks)
change the absolute number of subpopulations of T lymphocytes before treatment and on treatment	absolute number / mm 3 of different subpopulations of T lymphocyte	before treatment (week 0), at week 2, at week 12, at week 54 or at relapse (before 54 weeks)
change the absolute number of monocytes before treatment and on treatment	absolute number / mm 3 of monocytes	before treatment (week 0), at week 2, at week 12, at week 54 or at relapse (before 54 weeks)
change the percentage of cells producing cytokines in subpopulations of T lymphocytes before treatment and on treatment	% of cells producing cytokines in subpopulations of T lymphocytes	before treatment (week 0), at week 2, at week 12, at week 54 or at relapse (before 54 weeks)
change the percentage of cells producing cytokines in monocytes before treatment and on treatment	% of cells producing cytokines in monocytes	before treatment (week 0), at week 2, at week 12, at week 54 or at relapse (before 54 weeks)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
correlation between biological parameters and progression-free survival	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	progression between the date of first injection of immunotherapy and week 54 based on RECIST and ir-RECIST criterion
correlation between biological parameters on overall survival	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	death between the date of first injection of immunotherapy and week 54
Identify predictive factors of overall response rate at week 12 based on RECIST and ir-RECIST criteria	predictive factors like histological and cytological initial tumor type, initial immunological status will be evaluated at inclusion and correlated with the response	response evaluation at week 12
impact of treatments received prior to inclusion in the study on the biological parameters before and on treatment	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	antitumor treatment received from diagnosis of melanoma to inclusion
correlation between the occurrence of autoimmune side effects and the biological parameters before and on treatment	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	occurence of autoimmune side effects from day 0 to week 54

Collaborators and Investigators

• Sponsor: Hospices Civils de Lyon

Study record dates

Study Major Dates

• Study Start (Actual): April 23, 2015
• Primary Completion (Anticipated): April 1, 2018
• Study Completion (Anticipated): April 1, 2018

Study Registration Dates

• First Submitted: December 3, 2015
• First Submitted That Met QC Criteria: December 7, 2015
• First Posted (Estimate): December 10, 2015

Study Record Updates

• Last Update Posted (Actual): August 22, 2017
• Last Update Submitted That Met QC Criteria: August 18, 2017
• Last Verified: August 1, 2017

More Information

Terms related to this study

• Keywords: Melanoma; BRAF; Immune modulation; Anti-PD1 monoclonal antibodies
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Nevi and Melanomas; Melanoma; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Nivolumab
• Other Study ID Numbers: 2014.884