Clinical trial NCT03944356: BRAF-/MEK-Inhibition With Dabrafenib and Trametinib in Melanoma Patients
Official title: BRAF-/MEK-Inhibition With Dabrafenib and Trametinib in Melanoma Patients in the Adjuvant Setting: a Non-interventional Observatory Study
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Melanoma
Lead sponsor: EuMelaReg gGmbH
Sponsor class: INDUSTRY
First posted: 2019-05-09
Enrollment: 232
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
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.

Brief 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Median time on treatment
timeFrame: Date of first dose up to 12 months
Secondary outcomes:
measure: Permanent study drug discontinuation due to any reason
timeFrame: From date of first treatment until the date of treatment end, assessed up to 12 months
measure: Permanent study drug discontinuation due to adverse drug reactions
timeFrame: From date of first treatment until the date of treatment end, assessed up to 12 months
measure: Pyrexia and related symptoms
timeFrame: From date of first treatment until the date of treatment end, assessed up to 12 months
measure: Adverse drug reaction management: pyrexia
timeFrame: From date of first treatment until the date of treatment end, assessed up to 12 months
measure: Adverse drug reactions in Follow-up
timeFrame: From date of first treatment until the date of treatment end plus 3 months of follow-up, assessed up to 15 months
measure: Health-related quality of life
timeFrame: Over the course of treatment plus 3 months safety follow up, assessed up to 15 months
measure: Relapse free survival
timeFrame: From date of first treatment until the date of treatment end, assessed up to 12 months
measure: Distant metastasis free survival time
timeFrame: From date of first treatment until the date of treatment end, assessed up to 12 months
measure: Distant metastasis free survival rate
timeFrame: From date of first treatment until the date of treatment end, assessed up to 12 months
measure: Overall survival time
timeFrame: From date of first treatment until the date of treatment end, assessed up to 12 months
measure: Overall survival rate
timeFrame: From date of first treatment until the date of treatment end, assessed up to 12 months
measure: Time on treatment and efficacy endpoints
timeFrame: From date of first treatment until the date of treatment end, assessed up to 12 months
Other outcomes:
Locations:
city: Buxtehude
country: Germany
facility: Elbe Kliniken Stade - Buxtehude GmbH
state: Niedersachsen
city: Essen
country: Germany
facility: Universitätsklinikum Essen, Klinik und Poliklinik für Dermatologie, Venerologie und Allergologie
state: Nordrhein-Westfalen
city: Kiel
country: Germany
facility: Universitätsklinik Kiel, Klinik für Dermatologie, Venerologie und Allergologie
state: Schleswig-Holstein
city: Bochum
country: Germany
facility: Katholisches Klinikum Bochum
city: Bremen
country: Germany
facility: Klinikum Bremen Mitte gGmbH
city: Bremerhaven
country: Germany
facility: Klinikum Bremerhaven Reinkenheide gGmbH
city: Chemnitz
country: Germany
facility: DRK Krankenhaus Chemnitz Rabenstein
city: Darmstadt
country: Germany
facility: Klinikum Darmstadt GmbH
city: Dortmund
country: Germany
facility: Klinikum Dortmund gGmbH
city: Dresden
country: Germany
facility: Krankenhaus Dresden-Friedrichstadt
city: Dresden
country: Germany
facility: Universitätsklinik Dresden
city: Duisburg
country: Germany
facility: HELIOS St. Johannes Klinik Duisburg
city: Erfurt
country: Germany
facility: HELIOS Klinikum Erfurt
city: Erlangen
country: Germany
facility: Universitätsklinikum Erlangen
city: Freiburg
country: Germany
facility: Universitätsklinikum Freiburg
city: Gera
country: Germany
facility: SRH Wald-Klinikum Gera GmbH
city: Greifswald
country: Germany
facility: Universitätsklinikum Greifswald
city: Halle
country: Germany
facility: Universitätsklinik Halle
city: Hamburg
country: Germany
facility: Universitätsklinikum Hamburg-Eppendorf
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover
city: Heidelberg
country: Germany
facility: Universitätsklinikum Heidelberg
city: Karlsruhe
country: Germany
facility: Staedtisches Klinikum Karlsruhe
city: Leipzig
country: Germany
facility: Universitätsklinikum Leipzig
city: Ludwigshafen
country: Germany
facility: Klinikum Ludwigshafen gGmbH
city: Lübeck
country: Germany
facility: Universitätsklinikum Schleswig-Holstein
city: Magdeburg
country: Germany
facility: Universitätsklinik Magdeburg
city: Mannheim
country: Germany
facility: Universitaetsklinikum Mannheim
city: Minden
country: Germany
facility: Johannes Wesling Klinikum Minden
city: München
country: Germany
facility: Klinikum der Universität München
city: Münster
country: Germany
facility: Fachklinik Hornheide
city: Nürnberg
country: Germany
facility: Klinikum Nürnberg Nord
city: Quedlinburg
country: Germany
facility: Harzklinikum Dorothea Christiane Erxleben GmbH
city: Regensburg
country: Germany
facility: Universitätsklinikum Regensburg
city: Schwerin
country: Germany
facility: HELIOS Kliniken Schwerin
city: Tübingen
country: Germany
facility: Universitätsklinikum Tübingen
city: Ulm
country: Germany
facility: Universitätsklinikum Ulm
Study officials:
References: