MelanomaCombi-EUNCT03944356
BRAF-/MEK-Inhibition With Dabrafenib and Trametinib in Melanoma Patients
An observational study of Melanoma, run by EuMelaReg gGmbH at 36 sites in Germany.
Trial summary
Adjuvant therapy with dabrafenib plus trametinib in melanoma was approved in 2018 by the EMA (EUropean Medicines Agency). The purpose of this non-interventional study is to assess the usage of adjuvant dabrafenib and trametinib in clinical practice, where the patient population may differ from study population. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Melanoma
- What is being tested?
- Dabrafenib and Trametinib
- How many people
- 232 participants
- Where
- 36 sitesGermany
- Study dates
- 1 Jul 2019to 8 Oct 2024
- 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
- Adult, Older adult
Study population: Adult patients with complete surgical resection of histologically confirmed AJCC (8th edition) clinical stage III (IIIA, IIIB, IIIC, IIID) BRAF V600-mutated cutaneous melanoma who are planned to be treated or who already started treatment no longer than 4 weeks prior to study inclusion with dabrafenib and trametinib under routine conditions according to the applying SmPC.
Who may be able to join
- Patients with complete surgical resection of histologically confirmed AJCC (American Joint Committee on Cancer) (8th edition) clinical stage III (IIIA, IIIB, IIIC, IIID) melanoma, for whom a decision for adjuvant treatment with dabrafenib and trametinib has been made before entering the study.
- V600E/K mutation-positive cutaneous melanoma
- Adjuvant treatment with combination therapy of Dabrafenib (Tafinlar®) and Trametinib (Mekinist®) as indicated in the SmPC (Summary of Product Characteristics) and by prescription, that has been started no longer that 4 weeks before inclusion of the patient into the study or which will be initiated directly after inclusion
- Age ≥ 18 years
- Signed written informed consent
Who cannot join
- Lack of basic demographics and staging information
- Current or planned participation within a clinical trial. The participation in a follow-up phase of a clinical trial without active intervention is allowed.
- Current or planned treatment of another tumor disease except keratoacanthoma, squamous cell or basal cell carcinoma of the skin
Trial locations and contacts
36 sites in 1 country.
36 sites in 1 country
Germany36 sites
Katholisches Klinikum Bochum
Bochum, 44791
Klinikum Bremen Mitte gGmbH
Bremen, 28177
Klinikum Bremerhaven Reinkenheide gGmbH
Bremerhaven
Elbe Kliniken Stade - Buxtehude GmbH
Buxtehude, Lower Saxony, 21614
DRK Krankenhaus Chemnitz Rabenstein
Chemnitz, 09117
Klinikum Darmstadt GmbH
Darmstadt, 64297
Klinikum Dortmund gGmbH
Dortmund, 44137
Krankenhaus Dresden-Friedrichstadt
Dresden, 01067
Universitätsklinik Dresden
Dresden
HELIOS St. Johannes Klinik Duisburg
Duisburg, 47166
HELIOS Klinikum Erfurt
Erfurt, 99089
Universitätsklinikum Erlangen
Erlangen
Universitätsklinikum Essen, Klinik und Poliklinik für Dermatologie, Venerologie und Allergologie
Essen, North Rhine-Westphalia, 45147
Universitätsklinikum Freiburg
Freiburg im Breisgau
SRH Wald-Klinikum Gera GmbH
Gera, 07548
Universitätsklinikum Greifswald
Greifswald, 17475
Universitätsklinik Halle
Halle, 06120
Universitätsklinikum Hamburg-Eppendorf
Hamburg
Medizinische Hochschule Hannover
Hanover, 30625
Universitätsklinikum Heidelberg
Heidelberg, 69120
Staedtisches Klinikum Karlsruhe
Karlsruhe, 76133
Universitätsklinik Kiel, Klinik für Dermatologie, Venerologie und Allergologie
Kiel, Schleswig-Holstein, 24105
Universitätsklinikum Leipzig
Leipzig, 04103
Universitätsklinikum Schleswig-Holstein
Lübeck, 23568
Klinikum Ludwigshafen gGmbH
Ludwigshafen, 67063
Universitätsklinik Magdeburg
Magdeburg, 39120
Universitaetsklinikum Mannheim
Mannheim, 68167
Johannes Wesling Klinikum Minden
Minden, 32429
Klinikum der Universität München
München, 80337
Fachklinik Hornheide
Münster, 48157
Klinikum Nürnberg Nord
Nuremberg, 90419
Harzklinikum Dorothea Christiane Erxleben GmbH
Quedlinburg, 06484
Universitätsklinikum Regensburg
Regensburg, 93053
HELIOS Kliniken Schwerin
Schwerin, 19049
Universitätsklinikum Tübingen
Tübingen, 72076
Universitätsklinikum Ulm
Ulm
About this study
Official title: BRAF-/MEK-Inhibition With Dabrafenib and Trametinib in Melanoma Patients in the Adjuvant Setting: a Non-interventional Observatory Study
Adjuvant therapy with dabrafenib plus trametinib in melanoma was approved in 2018 by the EMA (EUropean Medicines Agency).
The purpose of this non-interventional study is to assess the usage of adjuvant dabrafenib and trametinib in clinical practice, where the patient population may differ from study population.
Read the detailed description
Melanoma is a disease of significant metastatic potential if not detected very early. Oncogenic mutations in BRAF (B-Raf proto-oncogene, serine/threonine kinase) are found in approximately 40% of melanomas and result in constitutive activation of the MAPK (Mitogen-Activated Protein Kinase) pathway.
Treatment with the BRAF inhibitor dabrafenib plus the MEK (Mitogen-activated protein kinase kinase) inhibitor trametinib showed improved overall survival in patients with unresectable or metastatic BRAF V600E/K-mutant melanoma (COMBI-d and COMBI-v studies). In an adjuvant setting treatment with dabrafenib and trametinib significantly reduced the risk of melanoma recurrence in patients with high-risk, stage III BRAF V600-mutant melanoma, with improvements in OS (Overall Survival), DMFS (Distant Metastasis Free Survival), and FFR (Freedom From Relaps) (COMBI-AD study). Based on these results, adjuvant dabrafenib plus trametinib therapy was approved in 2018 by the EMA.
Compared to the metastatic situation, issues of compliance and treatment adherence may be more relevant in adjuvant treatments, as patients are free of disease and potentially cured even without adjuvant treatment. As the routine administration of drugs including dosing, treatment interruptions, and early termination in clinical practice may vary from procedures defined in clinical trials, this study aims to assess the usage of adjuvant dabrafenib and trametinib in the routine clinical setting.
- Conditions
- Melanoma
- Being tested
- Dabrafenib and Trametinib
- Medical subject headings
- Melanoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Dabrafenib and TrametinibDrug
Also called Tafinlar and Mekinist
Dabrafenib and trametinib treatment under routine conditions according to the applying SmPC.
What is being measured
The primary outcome is the main question the study is designed to answer.
Median time on treatment
Median time on adjuvant dabrafenib + trametinib treatment defined as the interval between start of treatment and permanent discontinuation of treatment.
Measured: Date of first dose up to 12 months
Secondary outcomes (12)
Permanent study drug discontinuation due to any reason
Rate of permanent study drug discontinuation due to any reason.
Measured: From date of first treatment until the date of treatment end, assessed up to 12 months
Permanent study drug discontinuation due to adverse drug reactions
Rate of permanent study drug discontinuation due to adverse drug reactions (ADRs).
Measured: From date of first treatment until the date of treatment end, assessed up to 12 months
Pyrexia and related symptoms
Occurrence of pyrexia and related symptoms, listing the grade, number of episodes, and time to resolution.
Measured: From date of first treatment until the date of treatment end, assessed up to 12 months
Adverse drug reaction management: pyrexia
Type of adverse drug reaction (ADR) management applied for pyrexia and correlation with occurrence/persistence of pyrexia.
Measured: From date of first treatment until the date of treatment end, assessed up to 12 months
Adverse drug reactions in Follow-up
ADRs persisting/emerging up to 3 months post-treatment.
Measured: From date of first treatment until the date of treatment end plus 3 months of follow-up, assessed up to 15 months
Health-related quality of life
Assessment of health-related quality of life (HRQoL), measured by the European Organization for Research and Treatment of Cancer quality of life questionnaire (EORTC-QLQ-C30).
The EORTC QLQ-C30 consists of the folowing scales, with each dimension specifying five levels of severity [not at all (level 1), a little (level 2), quite a bit (level 3), very much (level 4)]:
- functional scales (Physical, Role, Cognitive, Emotional, Social Functioning)
- symptom scales (Fatigue, Pain and Nausea/Vomiting)
- single item scales (Dyspnoea, Insomnia, Appetite Loss, Constipation, Diarrhoea and Financial Difficulties).
Additionally the Global Health Status and QoL scales are incorporated, specifying on a scale from 1 (very poor) to 7 (excellent).
Measured: Over the course of treatment plus 3 months safety follow up, assessed up to 15 months
Relapse free survival
Relapse free survival (RFS) time and rate
Measured: From date of first treatment until the date of treatment end, assessed up to 12 months
Distant metastasis free survival time
Distant metastasis free survival (DMFS) time.
Measured: From date of first treatment until the date of treatment end, assessed up to 12 months
Distant metastasis free survival rate
Distant metastasis free survival (DMFS) rate.
Measured: From date of first treatment until the date of treatment end, assessed up to 12 months
Overall survival time
Overall survival (OS) time.
Measured: From date of first treatment until the date of treatment end, assessed up to 12 months
Overall survival rate
Overall survival (OS) rate.
Measured: From date of first treatment until the date of treatment end, assessed up to 12 months
Time on treatment and efficacy endpoints
Correlation between time on treatment and efficacy endpoints (RFS, DMFS, OS).
Measured: From date of first treatment until the date of treatment end, assessed up to 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 May 2019
- Study start1 Jul 2019
- Primary completion31 Dec 2023
- Study completion8 Oct 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for 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
- Case only
- Time perspective
- Prospective
- Enrolment
- 232 participants (actual)
Sponsor and investigators
- Lead sponsor
- EuMelaReg gGmbH
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03944356
- Sponsor's protocol ID
- EUMR-18001
- Acronym
- Combi-EU
- Status last verified
- Mar 2025
- First submitted
- 26 Apr 2019
- Last updated
- 12 Mar 2025
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 12 Mar 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- BRAF-/MEK-Inhibition With Dabrafenib and Trametinib in Melanoma Patients in the Adjuvant Setting: a Non-interventional Observatory Study
- ClinicalTrials.gov ID
- NCT03944356
- Acronym / sponsor ID
- Combi-EU / EUMR-18001
- Conditions
- Melanoma
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 232 participants (actual)
- Lead sponsor
- EuMelaReg gGmbHIndustry (pharma, biotech, devices)
- Study start
- 1 Jul 2019 (actual)
- Primary completion
- 31 Dec 2023 (actual)
- Study completion
- 8 Oct 2024 (actual)
- First posted
- 9 May 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.
Adjuvant therapy with dabrafenib plus trametinib in melanoma was approved in 2018 by the EMA (EUropean Medicines Agency).
The purpose of this non-interventional study is to assess the usage of adjuvant dabrafenib and trametinib in clinical practice, where the patient population may differ from study population.
Detailed description
Melanoma is a disease of significant metastatic potential if not detected very early. Oncogenic mutations in BRAF (B-Raf proto-oncogene, serine/threonine kinase) are found in approximately 40% of melanomas and result in constitutive activation of the MAPK (Mitogen-Activated Protein Kinase) pathway.
Treatment with the BRAF inhibitor dabrafenib plus the MEK (Mitogen-activated protein kinase kinase) inhibitor trametinib showed improved overall survival in patients with unresectable or metastatic BRAF V600E/K-mutant melanoma (COMBI-d and COMBI-v studies). In an adjuvant setting treatment with dabrafenib and trametinib significantly reduced the risk of melanoma recurrence in patients with high-risk, stage III BRAF V600-mutant melanoma, with improvements in OS (Overall Survival), DMFS (Distant Metastasis Free Survival), and FFR (Freedom From Relaps) (COMBI-AD study). Based on these results, adjuvant dabrafenib plus trametinib therapy was approved in 2018 by the EMA.
Compared to the metastatic situation, issues of compliance and treatment adherence may be more relevant in adjuvant treatments, as patients are free of disease and potentially cured even without adjuvant treatment. As the routine administration of drugs including dosing, treatment interruptions, and early termination in clinical practice may vary from procedures defined in clinical trials, this study aims to assess the usage of adjuvant dabrafenib and trametinib in the routine clinical setting.
Study design
- Observational model
- Case only
- Time perspective
- Prospective
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Age groups
- Adult, Older adult
- Study population
- Adult patients with complete surgical resection of histologically confirmed AJCC (8th edition) clinical stage III (IIIA, IIIB, IIIC, IIID) BRAF V600-mutated cutaneous melanoma who are planned to be treated or who already started treatment no longer than 4 weeks prior to study inclusion with dabrafenib and trametinib under routine conditions according to the applying SmPC.
Key inclusion criteria (5 listed)
- Patients with complete surgical resection of histologically confirmed AJCC (American Joint Committee on Cancer) (8th edition) clinical stage III (IIIA, IIIB, IIIC, IIID) melanoma, for whom a decision for adjuvant treatment with dabrafenib and trametinib has been made before entering the study.
- V600E/K mutation-positive cutaneous melanoma
- Adjuvant treatment with combination therapy of Dabrafenib (Tafinlar®) and Trametinib (Mekinist®) as indicated in the SmPC (Summary of Product Characteristics) and by prescription, that has been started no longer that 4 weeks before inclusion of the patient into the study or which will be initiated directly after inclusion
- Age ≥ 18 years
- Signed written informed consent
Key exclusion criteria (3 listed)
- Lack of basic demographics and staging information
- Current or planned participation within a clinical trial. The participation in a follow-up phase of a clinical trial without active intervention is allowed.
- Current or planned treatment of another tumor disease except keratoacanthoma, squamous cell or basal cell carcinoma of the skin
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Dabrafenib and TrametinibAlso: Tafinlar and MekinistDabrafenib and trametinib treatment under routine conditions according to the applying SmPC. | Drug | – |
Primary outcome
Median time on treatment
Time frame: Date of first dose up to 12 months
Median time on adjuvant dabrafenib + trametinib treatment defined as the interval between start of treatment and permanent discontinuation of treatment.
12 secondary outcomes
Permanent study drug discontinuation due to any reason
Time frame: From date of first treatment until the date of treatment end, assessed up to 12 months
Permanent study drug discontinuation due to adverse drug reactions
Time frame: From date of first treatment until the date of treatment end, assessed up to 12 months
Pyrexia and related symptoms
Time frame: From date of first treatment until the date of treatment end, assessed up to 12 months
Adverse drug reaction management: pyrexia
Time frame: From date of first treatment until the date of treatment end, assessed up to 12 months
Adverse drug reactions in Follow-up
Time frame: From date of first treatment until the date of treatment end plus 3 months of follow-up, assessed up to 15 months
Health-related quality of life
Time frame: Over the course of treatment plus 3 months safety follow up, assessed up to 15 months
Relapse free survival
Time frame: From date of first treatment until the date of treatment end, assessed up to 12 months
Distant metastasis free survival time
Time frame: From date of first treatment until the date of treatment end, assessed up to 12 months
Distant metastasis free survival rate
Time frame: From date of first treatment until the date of treatment end, assessed up to 12 months
Overall survival time
Time frame: From date of first treatment until the date of treatment end, assessed up to 12 months
Overall survival rate
Time frame: From date of first treatment until the date of treatment end, assessed up to 12 months
Time on treatment and efficacy endpoints
Time frame: From date of first treatment until the date of treatment end, assessed up to 12 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Mar 2025.
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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.
The record lists no contact. Use the official record to reach the sponsor.
36 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Melanoma, run by EuMelaReg gGmbH at 36 sites 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 5 inclusion and 3 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: finished, as of the sponsor's last update on 12 Mar 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 36 sites 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Median time on treatment (time frame: Date of first dose up to 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 12 Mar 2025.