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

NCT02626065 | Completed Phase 4

• 1 other identifier: 2014.884
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

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.

Conditions

Metastatic Melanoma

Keywords

Melanoma; Anti-PD1 monoclonal antibodies; Immune modulation; BRAF

Outcome Measures

Primary Outcomes (6)

• 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 Outcomes (5)

• 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

• correlation between biological parameters on 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

  response evaluation at week 12

• 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

• 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

Study Arms (2)

Nivolumab, patients with BRAF mutation

EXPERIMENTAL

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; Drug: Nivolumab

Nivolumab, patients with BRAF wild type

EXPERIMENTAL

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; Drug: Nivolumab

Interventions

blood sampling BIOLOGICAL

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)

Nivolumab, patients with BRAF mutation; Nivolumab, patients with BRAF wild type

Nivolumab DRUG

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.

Nivolumab, patients with BRAF mutation; Nivolumab, patients with BRAF wild type

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Hospices Civils de Lyon: lead

Study Sites (1)

Centre Hospitalier Lyon Sud

Pierre-Bénite, 69310, France

Location

Related Publications (1)

• Dalle S, Verronese E, N'Kodia A, Bardin C, Rodriguez C, Andrieu T, Eberhardt A, Chemin G, Hasan U, Le-Bouar M, Caramel J, Amini-Adle M, Bendriss-Vermare N, Dubois B, Caux C, Menetrier-Caux C. Modulation of blood T cell polyfunctionality and HVEM/BTLA expression are critical determinants of clinical outcome in anti-PD1-treated metastatic melanoma patients. Oncoimmunology. 2024 Jun 26;13(1):2372118. doi: 10.1080/2162402X.2024.2372118. eCollection 2024.

  PMID: 38939518 BACKGROUND

MeSH Terms

Conditions

Melanoma

Interventions

Blood Specimen Collection; Nivolumab

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 3, 2015
• First Posted: December 10, 2015
• Study Start: April 23, 2015
• Primary Completion: December 28, 2017
• Study Completion: December 28, 2017
• Last Updated: September 15, 2025

Record last verified: 2025-09

Locations

FR (1)