Metastatic MelanomaNCT04158544
Immune Monitoring in Metastatic Melanoma
An observational study of Metastatic Melanoma, run by University of Regensburg at 1 site in Germany.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Metastatic Melanoma
- How many people
- 100 participants
- Where
- 1 siteGermany
- Study dates
- 1 Aug 2016to 31 Jul 2021
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Patients with metastatic melanoma of all ages and both sexes will be screened for inclusion if they qualify for systemic therapy.
Who may be able to join
- Presence of metastatic melanoma expecting treatment with immune or targeted therapy
Who cannot join
- <18 years
Trial locations and contacts
1 site in 1 country.
Germany1 site, 1 recruiting
- Recruiting
Dept. of Dermatology; Univeristy Hospital Regensburg
Regensburg, Bavaria, 93053
Sebastian Haferkamp, MD, +499419440, Sebastian.Haferkamp@klinik.uni-regensburg.de
About this study
Official title: Immune Monitoring During Systemic Therapy of Metastatic Malignant Melanoma
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).
Read more
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.
Read the detailed description
Despite recent breakthroughs in the treatment of melanoma, the prognosis in the advanced stage of the disease continues to be very poor. 45-50% of all melanomas carry a point mutation in codon 600 of the BRAF gene encoding a serine-threonine kinase. The two most common BRAF mutations (V600E and V600K) constitutively activate the MAP kinase signaling pathway that drives the proliferation and survival of cancer cells. Specific BRAF V600 inhibitors such as vemurafenib, dabrafenib and encorafenib and inhibitors of the downstream target MEK such as trametinib, binimetinib and cobimetinib are very effective regimens in BRAF-positive metastatic melanoma.
Recent studies have shown that these inhibitors in addition to the effects on the tumor cells also have an influence on cells of the immune system. For example, vemurafenib leads to a loss of peripheral blood lymphocytes. Thus, the number of peripheral CD4 + positive cells decreases with vemurafenib therapy, while the number of natural killer cells (NK cells) increases. On the other hand, initial studies show that B cells and CD8 + positive cells are not affected numerically by vemurafenib. It has been demonstrated that vemurafenib but not dabrafenib reduces the number of peripheral lymphocytes in melanoma patients and changes the function and phenotype of CD4 + positive cells, although both drugs show comparable clinical efficacy. Selective inhibition of BRAF by inhibitors such as vemurafenib or dabrafenib thus has a significant influence on the peripheral lymphocyte populations of melanoma patients. Studies have been demonstrated that inhibition of BRAF can induce increased invasion of tumor-infiltrating lymphocytes into melanoma metastases. Tumor infiltration of CD4 + and CD8 + positive lymphocytes is surprisingly enhanced by therapy with a BRAF inhibitor. Furthermore, it could be shown in this study that the number of immunoreactive cells correlated with a reduction in tumor size and an increased necrosis in the tumor areas. The data obtained so far suggest that treatment with BRAF inhibitors increases melanoma antigen expression and thus facilitates T cell cytotoxicity. This results in a more favorable tumor microenvironment for a synergistic BRAF-targeted therapy and immunotherapy. This therapeutic strategy is currently being evaluated in clinical trials.
The group of immunotherapeutics is a second new class of drugs, in which great hope for the treatment of metastatic melanoma is placed. Ipilimumab is an antibody that binds the cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), thereby stimulating T-cell activation and proliferation. The drug has been approved for the treatment of metastatic melanoma since July 2011 and significantly increases survival in some patients. In addition, at the end of 2015, a monoclonal antibody directed against the Programmed Death Receptor (PD1) was approved by the European Medicines Commission for the treatment of unresectable or metastatic melanoma. PD1 is a receptor that is expressed on T cells and inhibits T cell activation upon binding of a ligand. Study results have shown that blocking this T-cell inhibition with PD1 or PD-L1 antagonists is a very effective therapeutic strategy for melanoma and other tumor entities.
Current data show that targeted therapy has a major impact on the tumor microenvironment and on the regulatory and effector cells of the immune system. 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.
In the context of this study, the immune status, e.g. the number and the activation state of different immune cells at the beginning and in the course of a systemic therapy for metastatic melanoma should be determined. For this purpose, 10 ml of EDTA blood is taken as part of the guideline-compliant routine care (The blood samples taken in the study are given every 4 weeks for therapy with kinase inhibitors and every 2 weeks for therapy with checkpoint inhibitors). The blood samples taken before and during therapy will be analyzed by flow cytometry and the changes in the immunophenotype will be correlated with the response to therapy. In this way, the investigator want to identify both predictive and prognostic markers. The assessment of the immune status should help to optimize the effectiveness of melanoma therapy. Therefore, it would be important to identify suitable markers and to characterize subgroups of immune cells that have an impact on the tumor microenvironment.
The evaluation of the immune status in melanoma patients could thus be incorporated into the treatment strategies in the future in order to combine a targeted therapy with immunomodulating substances or also from enriched sub-populations of immune cells in order to increase the effectiveness of the treatment.
- Conditions
- Metastatic Melanoma
- Keywords
- Immune monitoring, Immunotherapy
- Medical subject headings
- Melanoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Checkpoint Inhibitors | Patients with metastatic melanoma receiving systemic therapy with checkpoint inhibitors | |
| Kinase Inhibitors | Patients with metastatic melanoma receiving systemic therapy with kinase inhibitors |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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)
Screening for liver inflammation (serum ALT U/l)
Measured: 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)
Screening for liver inflammation (serum AST U/l)
Measured: Before start of treatment, 3 and 6 weeks after start of treatment as well as through study completion, an average of 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Nov 2019
- Study start1 Aug 2016
- Primary completion31 Jul 2020 (estimated)
- Study completion31 Jul 2021 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (10)Papers the sponsor has linked to this study.
- Other trials for Metastatic MelanomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Regensburg
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Edward Geissler, University of Regensburg
- Investigators
- Edward K Geissler, Phd, Principal investigator, Dept. of Exp. Surgery, University Hospital Regensburg
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04158544
- Sponsor's protocol ID
- 16-101-0125
- Status last verified
- Nov 2019
- First submitted
- 23 Oct 2019
- Last updated
- 8 Nov 2019
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
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.
PubMed 21639808Board 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.
PubMed 19861964Schilling 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.
PubMed 24167759Schilling 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.
PubMed 23526263Schilling 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.
PubMed 24504444Wilmott 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.
PubMed 22156613Frederick 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.
PubMed 23307859Robert 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.
PubMed 25034862Merelli 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.
PubMed 24029602Streitz 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.
PubMed 24160259
Study at a glance
From the registry record, last updated by the sponsor on 8 Nov 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Immune Monitoring During Systemic Therapy of Metastatic Malignant Melanoma
- ClinicalTrials.gov ID
- NCT04158544
- Acronym / sponsor ID
- 16-101-0125
- Conditions
- Metastatic Melanoma
- Keywords
- Immune monitoring, Immunotherapy
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- University of RegensburgUniversity, hospital or other
- Study start
- 1 Aug 2016 (actual)
- Primary completion
- 31 Jul 2020 (estimated)
- Study completion
- 31 Jul 2021 (estimated)
- First posted
- 8 Nov 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Despite recent breakthroughs in the treatment of melanoma, the prognosis in the advanced stage of the disease continues to be very poor. 45-50% of all melanomas carry a point mutation in codon 600 of the BRAF gene encoding a serine-threonine kinase. The two most common BRAF mutations (V600E and V600K) constitutively activate the MAP kinase signaling pathway that drives the proliferation and survival of cancer cells. Specific BRAF V600 inhibitors such as vemurafenib, dabrafenib and encorafenib and inhibitors of the downstream target MEK such as trametinib, binimetinib and cobimetinib are very effective regimens in BRAF-positive metastatic melanoma.
Recent studies have shown that these inhibitors in addition to the effects on the tumor cells also have an influence on cells of the immune system. For example, vemurafenib leads to a loss of peripheral blood lymphocytes. Thus, the number of peripheral CD4 + positive cells decreases with vemurafenib therapy, while the number of natural killer cells (NK cells) increases. On the other hand, initial studies show that B cells and CD8 + positive cells are not affected numerically by vemurafenib. It has been demonstrated that vemurafenib but not dabrafenib reduces the number of peripheral lymphocytes in melanoma patients and changes the function and phenotype of CD4 + positive cells, although both drugs show comparable clinical efficacy. Selective inhibition of BRAF by inhibitors such as vemurafenib or dabrafenib thus has a significant influence on the peripheral lymphocyte populations of melanoma patients. Studies have been demonstrated that inhibition of BRAF can induce increased invasion of tumor-infiltrating lymphocytes into melanoma metastases. Tumor infiltration of CD4 + and CD8 + positive lymphocytes is surprisingly enhanced by therapy with a BRAF inhibitor. Furthermore, it could be shown in this study that the number of immunoreactive cells correlated with a reduction in tumor size and an increased necrosis in the tumor areas. The data obtained so far suggest that treatment with BRAF inhibitors increases melanoma antigen expression and thus facilitates T cell cytotoxicity. This results in a more favorable tumor microenvironment for a synergistic BRAF-targeted therapy and immunotherapy. This therapeutic strategy is currently being evaluated in clinical trials.
The group of immunotherapeutics is a second new class of drugs, in which great hope for the treatment of metastatic melanoma is placed. Ipilimumab is an antibody that binds the cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), thereby stimulating T-cell activation and proliferation. The drug has been approved for the treatment of metastatic melanoma since July 2011 and significantly increases survival in some patients. In addition, at the end of 2015, a monoclonal antibody directed against the Programmed Death Receptor (PD1) was approved by the European Medicines Commission for the treatment of unresectable or metastatic melanoma. PD1 is a receptor that is expressed on T cells and inhibits T cell activation upon binding of a ligand. Study results have shown that blocking this T-cell inhibition with PD1 or PD-L1 antagonists is a very effective therapeutic strategy for melanoma and other tumor entities.
Current data show that targeted therapy has a major impact on the tumor microenvironment and on the regulatory and effector cells of the immune system. 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.
In the context of this study, the immune status, e.g. the number and the activation state of different immune cells at the beginning and in the course of a systemic therapy for metastatic melanoma should be determined. For this purpose, 10 ml of EDTA blood is taken as part of the guideline-compliant routine care (The blood samples taken in the study are given every 4 weeks for therapy with kinase inhibitors and every 2 weeks for therapy with checkpoint inhibitors). The blood samples taken before and during therapy will be analyzed by flow cytometry and the changes in the immunophenotype will be correlated with the response to therapy. In this way, the investigator want to identify both predictive and prognostic markers. The assessment of the immune status should help to optimize the effectiveness of melanoma therapy. Therefore, it would be important to identify suitable markers and to characterize subgroups of immune cells that have an impact on the tumor microenvironment.
The evaluation of the immune status in melanoma patients could thus be incorporated into the treatment strategies in the future in order to combine a targeted therapy with immunomodulating substances or also from enriched sub-populations of immune cells in order to increase the effectiveness of the treatment.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Checkpoint Inhibitors | – | –Patients with metastatic melanoma receiving systemic therapy with checkpoint inhibitors |
| Kinase Inhibitors | – | –Patients with metastatic melanoma receiving systemic therapy with kinase inhibitors |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Patients with metastatic melanoma of all ages and both sexes will be screened for inclusion if they qualify for systemic therapy.
Key inclusion criteria (1 listed)
- Presence of metastatic melanoma expecting treatment with immune or targeted therapy
Key exclusion criteria (1 listed)
- <18 years
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Change in frequency of peripheral immune cell populations assessed by immune monitoring through flow cytometry (ONE study FACS panel)
Time frame: Before start of treatment, 3 and 6 weeks after start of treatment as well as through study completion, an average of 1 year
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.
Change in activation status of peripheral immune cell populations assessed by immune monitoring through flow cytometry (ONE study FACS panel)
Time frame: Before start of treatment, 3 and 6 weeks after start of treatment as well as through study completion, an average of 1 year
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.
2 secondary outcomes
Liver inflammation (ALT)
Time frame: 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)
Time frame: Before start of treatment, 3 and 6 weeks after start of treatment as well as through study completion, an average of 1 year
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Nov 2019.
- Background: PubMed 21639808Chapman 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.
- Background: PubMed 19861964Board 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.
- Background: PubMed 24167759Schilling 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.
- Background: PubMed 23526263Schilling 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.
- Background: PubMed 24504444Schilling 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.
- Background: PubMed 22156613Wilmott 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.
- Background: PubMed 23307859Frederick 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.
- Background: PubMed 25034862Robert 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.
- Background: PubMed 24029602Merelli 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.
- Background: PubMed 24160259Streitz 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.
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Unresectable or Metastatic Melanoma
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Edward K Geissler, Phd principal investigator
Dept. of Exp. Surgery, University Hospital Regensburg
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Metastatic Melanoma, run by University of Regensburg at 1 site in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 8 Nov 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Sebastian Haferkamp (+499419440, Sebastian.Haferkamp@klinik.uni-regensburg.de), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in frequency of peripheral immune cell populations assessed by immune monitoring through flow cytometry (ONE study FACS panel) (time frame: Before start of treatment, 3 and 6 weeks after start of treatment as well as through study completion, an average of 1 year). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04158544, which also lists 10 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Nov 2019.