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

• ClinicalTrials.gov Identifier: NCT02626065
• Recruitment Status: Unknown
• First Posted: December 10, 2015
• Last Update Posted: August 22, 2017
• Sponsor: Hospices Civils de Lyon
• Information provided by (Responsible Party): Hospices Civils de Lyon

Tracking Information

• First Submitted Date: December 3, 2015
• First Posted Date: December 10, 2015
• Last Update Posted Date: August 22, 2017
• Actual Study Start Date: April 23, 2015
• Estimated Primary Completion Date: April 2018 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: December 7, 2015)

• change the absolute number of dendritic cells before treatment and on treatment [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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
• change the percentage of cells producing cytokines in monocytes before treatment and on treatment [ Time Frame: 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

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: December 7, 2015)

• correlation between biological parameters and progression-free survival [ Time Frame: 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
• correlation between biological parameters on overall survival [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Immune Modulation Study in Patients With Metastatic Melanoma Treated With Anti-PD1 Monoclonal Antibodies
• Official Title: Immune Modulation Study in Patients With Metastatic Melanoma Treated With Anti-PD1 Monoclonal Antibodies
• 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 4
• Study Design: Allocation: Non-Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Other
• Condition: Metastatic Melanoma

Intervention

• 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.

Study Arms

• 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

  Interventions:

  • Biological: blood sampling
  • Drug: Nivolumab
• 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

  Interventions:

  • Biological: blood sampling
  • Drug: Nivolumab

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Unknown status
• Actual Enrollment (submitted: August 18, 2017): 32
• Original Estimated Enrollment (submitted: December 7, 2015): 40
• Estimated Study Completion Date: April 2018
• Estimated Primary Completion Date: April 2018 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: France

Administrative Information

• NCT Number: NCT02626065
• Other Study ID Numbers: 2014.884
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Hospices Civils de Lyon
• Study Sponsor: Hospices Civils de Lyon
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Hospices Civils de Lyon
• Verification Date: August 2017