BRAF-/MEK-Inhibition With Dabrafenib and Trametinib in Melanoma Patients (Combi-EU)

March 10, 2025 updated by: EuMelaReg gGmbH

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 Type

Observational

Enrollment (Actual)

232

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Germany
      • Bochum, Germany, 44791
        • Katholisches Klinikum Bochum
      • Bremen, Germany, 28177
        • Klinikum Bremen Mitte gGmbH
      • Bremerhaven, Germany
        • Klinikum Bremerhaven Reinkenheide gGmbH
      • Chemnitz, Germany, 09117
        • DRK Krankenhaus Chemnitz Rabenstein
      • Darmstadt, Germany, 64297
        • Klinikum Darmstadt GmbH
      • Dortmund, Germany, 44137
        • Klinikum Dortmund gGmbH
      • Dresden, Germany, 01067
        • Krankenhaus Dresden-Friedrichstadt
      • Dresden, Germany
        • Universitatsklinik Dresden
      • Duisburg, Germany, 47166
        • HELIOS St. Johannes Klinik Duisburg
      • Erfurt, Germany, 99089
        • HELIOS Klinikum Erfurt
      • Erlangen, Germany
        • Universitatsklinikum Erlangen
      • Freiburg, Germany
        • Universitatsklinikum Freiburg
      • Gera, Germany, 07548
        • SRH Wald-Klinikum Gera GmbH
      • Greifswald, Germany, 17475
        • Universitätsklinikum Greifswald
      • Halle, Germany, 06120
        • Universitätsklinik Halle
      • Hamburg, Germany
        • Universitatsklinikum Hamburg-Eppendorf
      • Hannover, Germany, 30625
        • Medizinische Hochschule Hannover
      • Heidelberg, Germany, 69120
        • UniversitatsKlinikum Heidelberg
      • Karlsruhe, Germany, 76133
        • Staedtisches Klinikum Karlsruhe
      • Leipzig, Germany, 04103
        • Universitätsklinikum Leipzig
      • Ludwigshafen, Germany, 67063
        • Klinikum Ludwigshafen gGmbH
      • Lübeck, Germany, 23568
        • Universitätsklinikum Schleswig-Holstein
      • Magdeburg, Germany, 39120
        • Universitätsklinik Magdeburg
      • Mannheim, Germany, 68167
        • Universitaetsklinikum Mannheim
      • Minden, Germany, 32429
        • Johannes Wesling Klinikum Minden
      • München, Germany, 80337
        • Klinikum der Universität München
      • Münster, Germany, 48157
        • Fachklinik Hornheide
      • Nürnberg, Germany, 90419
        • Klinikum Nurnberg Nord
      • Quedlinburg, Germany, 06484
        • Harzklinikum Dorothea Christiane Erxleben GmbH
      • Regensburg, Germany, 93053
        • Universitätsklinikum Regensburg
      • Schwerin, Germany, 19049
        • Helios Kliniken Schwerin
      • Tübingen, Germany, 72076
        • Universitatsklinikum Tubingen
      • Ulm, Germany
        • Universitatsklinikum Ulm
    • Niedersachsen
      • Buxtehude, Niedersachsen, Germany, 21614
        • Elbe Kliniken Stade - Buxtehude GmbH
    • Nordrhein-Westfalen
      • Essen, Nordrhein-Westfalen, Germany, 45147
        • Universitätsklinikum Essen, Klinik und Poliklinik für Dermatologie, Venerologie und Allergologie
    • Schleswig-Holstein
      • Kiel, Schleswig-Holstein, Germany, 24105
        • Universitätsklinik Kiel, Klinik für Dermatologie, Venerologie und Allergologie

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

14 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

N/A

Sampling Method

Non-Probability Sample

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.

Description

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Case-Only
  • Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Date of first dose up to 12 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
Rate of permanent study drug discontinuation due to any reason.
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
Rate of permanent study drug discontinuation due to adverse drug reactions (ADRs).
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
Occurrence of pyrexia and related symptoms, listing the grade, number of episodes, and time to resolution.
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
Type of adverse drug reaction (ADR) management applied for pyrexia and correlation with occurrence/persistence of pyrexia.
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
ADRs persisting/emerging up to 3 months post-treatment.
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

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).
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
Relapse free survival (RFS) time and rate
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 (DMFS) time.
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
Distant metastasis free survival (DMFS) rate.
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 (OS) time.
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
Overall survival (OS) rate.
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
Correlation between time on treatment and efficacy endpoints (RFS, DMFS, OS).
From date of first treatment until the date of treatment end, assessed up to 12 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

EuMelaReg gGmbH

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 1, 2019

Primary Completion (Actual)

December 31, 2023

Study Completion (Actual)

October 8, 2024

Study Registration Dates

First Submitted

April 26, 2019

First Submitted That Met QC Criteria

May 8, 2019

First Posted (Actual)

May 9, 2019

Study Record Updates

Last Update Posted (Actual)

March 25, 2025

Last Update Submitted That Met QC Criteria

March 10, 2025

Last Verified

March 1, 2025

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • EUMR-18001

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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