Immune Monitoring in Metastatic Melanoma

NCT04158544 | Unknown

• 1 other identifier: 16-101-0125
• Study Type: observational
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

The mean survival time in the advanced tumor stage in the presence of distant metastases in malignant melanoma was less than 9 months until a few years ago. Intensive research efforts have led to the development of promising new therapeutic strategies and their clinical application. These include on the one hand mutation-specific inhibitors of important for cell division serine-threonine kinase BRAF such as vemurafenib, dabrafenib and encorafenib and inhibitors of the downstream target protein, the mitogen-activated protein kinase kinase (MEK), such as trametinib, binimetinib and cobimetinib. The group of immunotherapeutics is a second new class of drugs, in which great hope for the treatment of metastatic melanoma is placed. Antibody-mediated blockage of surface molecules expressed on immune cells, referred to as immune checkpoints, results in activation of the immune system. As a result, an anti-tumor immune response is triggered, which has led to considerable therapeutic success in metastatic melanoma. To date, three checkpoint inhibitors have been approved for the treatment of metastatic melanoma. Ipilimumab is an antibody that binds cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4); Pembrolizumab and nivolumab cause immune stimulation by binding the Programmed Death Receptor (PD1). However, the impact of the therapy on the immune system as a whole is largely unknown. A comprehensive understanding of these effects is crucial to be able to further develop the therapy and to evaluate useful combination therapies with other immunomodulatory agents. Within the framework of this project changes of the immune response under a systemic therapy of the malignant melanoma are to be characterized. The material for the analysis comes from blood samples collected during routine patient check-ups. The aim of the analyzes is to precisely characterize the effects of the different therapeutics on the function of the immune system. In particular, the study will investigate whether certain therapeutic agents can weaken or activate the immune system and thus, in addition to the direct effect on the tumor cells, mediate indirect therapeutic effects via immune modulation. In the long term, the investigators want to use the knowledge gained to further improve the already existing therapeutic strategies of malignant melanoma by additional modulation of the immune system.

Conditions

Metastatic Melanoma

Keywords

Immune monitoring; Immunotherapy

Outcome Measures

Primary Outcomes (2)

• Change in frequency of peripheral immune cell populations assessed by immune monitoring through flow cytometry (ONE study FACS panel)

  As part of the course of therapy during routine check-up, blood samples are collected and then analyzed by flow cytometry (ONE study panel). Frequency of surface antigens of PBMC are analyzed and the characterized sub-populations are monitored during the follow-up. Thereby, changes in frequency of surface antigens will be assessed compared to baseline (before start of treatment). This allows to determine the individual immunophenotype of a patient.

  Before start of treatment, 3 and 6 weeks after start of treatment as well as through study completion, an average of 1 year

• Change in activation status of peripheral immune cell populations assessed by immune monitoring through flow cytometry (ONE study FACS panel)

  As part of the course of therapy during routine check-up, blood samples are collected and then analyzed by flow cytometry (ONE study panel). Expression level of surface antigens of PBMC are analyzed and the characterized sub-populations are monitored during the follow-up. Thereby, changes in expression level of surface antigens will be assessed compared to baseline (before start of treatment). This allows to determine the individual immunophenotype of a patient.

  Before start of treatment, 3 and 6 weeks after start of treatment as well as through study completion, an average of 1 year

Secondary Outcomes (2)

• Liver inflammation (ALT)

  Before start of treatment, 3 and 6 weeks after start of treatment as well as through study completion, an average of 1 year

• Liver inflammation (AST)

  Before start of treatment, 3 and 6 weeks after start of treatment as well as through study completion, an average of 1 year

Study Arms (2)

Checkpoint Inhibitors

Patients with metastatic melanoma receiving systemic therapy with checkpoint inhibitors

Kinase Inhibitors

Patients with metastatic melanoma receiving systemic therapy with kinase inhibitors

Eligibility Criteria

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

Study Population

Patients with metastatic melanoma of all ages and both sexes will be screened for inclusion if they qualify for systemic therapy.

You may qualify if:

• Presence of metastatic melanoma expecting treatment with immune or targeted therapy

You may not qualify if:

• \<18 years

Sponsors & Collaborators

• University of Regensburg: lead

Study Sites (1)

Dept. of Dermatology; Univeristy Hospital Regensburg

Regensburg, Bavaria, 93053, Germany

RECRUITING

Related Publications (10)

• Chapman PB, Hauschild A, Robert C, Haanen JB, Ascierto P, Larkin J, Dummer R, Garbe C, Testori A, Maio M, Hogg D, Lorigan P, Lebbe C, Jouary T, Schadendorf D, Ribas A, O'Day SJ, Sosman JA, Kirkwood JM, Eggermont AM, Dreno B, Nolop K, Li J, Nelson B, Hou J, Lee RJ, Flaherty KT, McArthur GA; BRIM-3 Study Group. Improved survival with vemurafenib in melanoma with BRAF V600E mutation. N Engl J Med. 2011 Jun 30;364(26):2507-16. doi: 10.1056/NEJMoa1103782. Epub 2011 Jun 5.

  PMID: 21639808 BACKGROUND

• Board RE, Ellison G, Orr MC, Kemsley KR, McWalter G, Blockley LY, Dearden SP, Morris C, Ranson M, Cantarini MV, Dive C, Hughes A. Detection of BRAF mutations in the tumour and serum of patients enrolled in the AZD6244 (ARRY-142886) advanced melanoma phase II study. Br J Cancer. 2009 Nov 17;101(10):1724-30. doi: 10.1038/sj.bjc.6605371. Epub 2009 Oct 27.

  PMID: 19861964 BACKGROUND

• Schilling B, Paschen A. Immunological consequences of selective BRAF inhibitors in malignant melanoma: Neutralization of myeloid-derived suppressor cells. Oncoimmunology. 2013 Aug 1;2(8):e25218. doi: 10.4161/onci.25218. Epub 2013 Jun 10.

  PMID: 24167759 BACKGROUND

• Schilling B, Sucker A, Griewank K, Zhao F, Weide B, Gorgens A, Giebel B, Schadendorf D, Paschen A. Vemurafenib reverses immunosuppression by myeloid derived suppressor cells. Int J Cancer. 2013 Oct 1;133(7):1653-63. doi: 10.1002/ijc.28168. Epub 2013 Apr 13.

  PMID: 23526263 BACKGROUND

• Schilling B, Sondermann W, Zhao F, Griewank KG, Livingstone E, Sucker A, Zelba H, Weide B, Trefzer U, Wilhelm T, Loquai C, Berking C, Hassel J, Kahler KC, Utikal J, Al Ghazal P, Gutzmer R, Goldinger SM, Zimmer L, Paschen A, Hillen U, Schadendorf D; DeCOG. Differential influence of vemurafenib and dabrafenib on patients' lymphocytes despite similar clinical efficacy in melanoma. Ann Oncol. 2014 Mar;25(3):747-753. doi: 10.1093/annonc/mdt587. Epub 2014 Feb 6.

  PMID: 24504444 BACKGROUND

• Wilmott JS, Long GV, Howle JR, Haydu LE, Sharma RN, Thompson JF, Kefford RF, Hersey P, Scolyer RA. Selective BRAF inhibitors induce marked T-cell infiltration into human metastatic melanoma. Clin Cancer Res. 2012 Mar 1;18(5):1386-94. doi: 10.1158/1078-0432.CCR-11-2479. Epub 2011 Dec 12.

  PMID: 22156613 BACKGROUND

• Frederick DT, Piris A, Cogdill AP, Cooper ZA, Lezcano C, Ferrone CR, Mitra D, Boni A, Newton LP, Liu C, Peng W, Sullivan RJ, Lawrence DP, Hodi FS, Overwijk WW, Lizee G, Murphy GF, Hwu P, Flaherty KT, Fisher DE, Wargo JA. BRAF inhibition is associated with enhanced melanoma antigen expression and a more favorable tumor microenvironment in patients with metastatic melanoma. Clin Cancer Res. 2013 Mar 1;19(5):1225-31. doi: 10.1158/1078-0432.CCR-12-1630. Epub 2013 Jan 10.

  PMID: 23307859 BACKGROUND

• Robert C, Ribas A, Wolchok JD, Hodi FS, Hamid O, Kefford R, Weber JS, Joshua AM, Hwu WJ, Gangadhar TC, Patnaik A, Dronca R, Zarour H, Joseph RW, Boasberg P, Chmielowski B, Mateus C, Postow MA, Gergich K, Elassaiss-Schaap J, Li XN, Iannone R, Ebbinghaus SW, Kang SP, Daud A. Anti-programmed-death-receptor-1 treatment with pembrolizumab in ipilimumab-refractory advanced melanoma: a randomised dose-comparison cohort of a phase 1 trial. Lancet. 2014 Sep 20;384(9948):1109-17. doi: 10.1016/S0140-6736(14)60958-2. Epub 2014 Jul 15.

  PMID: 25034862 BACKGROUND

• Merelli B, Massi D, Cattaneo L, Mandala M. Targeting the PD1/PD-L1 axis in melanoma: biological rationale, clinical challenges and opportunities. Crit Rev Oncol Hematol. 2014 Jan;89(1):140-65. doi: 10.1016/j.critrevonc.2013.08.002. Epub 2013 Aug 28.

  PMID: 24029602 BACKGROUND

• Streitz M, Miloud T, Kapinsky M, Reed MR, Magari R, Geissler EK, Hutchinson JA, Vogt K, Schlickeiser S, Kverneland AH, Meisel C, Volk HD, Sawitzki B. Standardization of whole blood immune phenotype monitoring for clinical trials: panels and methods from the ONE study. Transplant Res. 2013 Oct 25;2(1):17. doi: 10.1186/2047-1440-2-17.

  PMID: 24160259 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

blood samples (10ml EDTA)

MeSH Terms

Conditions

Melanoma

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

Study Officials

• Edward K Geissler, Phd

  Dept. of Exp. Surgery, University Hospital Regensburg

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Sebastian Haferkamp

CONTACT

+499419440; Sebastian.Haferkamp@klinik.uni-regensburg.de

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Head of Experimental Surgery

Study Record Dates

• First Submitted: October 23, 2019
• First Posted: November 8, 2019
• Study Start: August 1, 2016
• Primary Completion: July 31, 2020
• Study Completion: July 31, 2021
• Last Updated: November 8, 2019

Record last verified: 2019-11

Locations

DE (1)