BRAF-/MEK-Inhibition With Dabrafenib and Trametinib in Melanoma Patients

Melanoma Clinical Trial

— Combi-EU  

Official title:

BRAF-/MEK-Inhibition With Dabrafenib and Trametinib in Melanoma Patients in the Adjuvant Setting: a Non-interventional Observatory Study

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03944356
• Other study ID #: EUMR-18001
• Status: Active, not recruiting
• Start date: July 1, 2019
• Est. completion date: June 2024

Study information

• Verified date: August 2022
• Source: EuMelaReg gGmbH
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 232
• Est. completion date: June 2024
• Est. primary completion date: December 2023
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Melanoma

Intervention

Drug:
• Dabrafenib and Trametinib
Dabrafenib and trametinib treatment under routine conditions according to the applying SmPC.

Locations

Country	Name	City	State
Germany	Katholisches Klinikum Bochum	Bochum
Germany	Klinikum Bremen Mitte gGmbH	Bremen
Germany	Klinikum Bremerhaven Reinkenheide gGmbH	Bremerhaven
Germany	Elbe Kliniken Stade - Buxtehude GmbH	Buxtehude	Niedersachsen
Germany	DRK Krankenhaus Chemnitz Rabenstein	Chemnitz
Germany	Klinikum Darmstadt GmbH	Darmstadt
Germany	Klinikum Dortmund gGmbH	Dortmund
Germany	Krankenhaus Dresden-Friedrichstadt	Dresden
Germany	Universitätsklinik Dresden	Dresden
Germany	HELIOS St. Johannes Klinik Duisburg	Duisburg
Germany	HELIOS Klinikum Erfurt	Erfurt
Germany	Universitätsklinikum Erlangen	Erlangen
Germany	Universitätsklinikum Essen, Klinik und Poliklinik für Dermatologie, Venerologie und Allergologie	Essen	Nordrhein-Westfalen
Germany	Universitätsklinikum Freiburg	Freiburg
Germany	SRH Wald-Klinikum Gera GmbH	Gera
Germany	Universitätsklinikum Greifswald	Greifswald
Germany	Universitätsklinik Halle	Halle
Germany	Universitätsklinikum Hamburg-Eppendorf	Hamburg
Germany	Medizinische Hochschule Hannover	Hannover
Germany	Universitätsklinikum Heidelberg	Heidelberg
Germany	Staedtisches Klinikum Karlsruhe	Karlsruhe
Germany	Universitätsklinik Kiel, Klinik für Dermatologie, Venerologie und Allergologie	Kiel	Schleswig-Holstein
Germany	Universitätsklinikum Leipzig	Leipzig
Germany	Universitätsklinikum Schleswig-Holstein	Lübeck
Germany	Klinikum Ludwigshafen gGmbH	Ludwigshafen
Germany	Universitätsklinik Magdeburg	Magdeburg
Germany	Universitaetsklinikum Mannheim	Mannheim
Germany	Johannes Wesling Klinikum Minden	Minden
Germany	Klinikum der Universität München	München
Germany	Fachklinik Hornheide	Münster
Germany	Klinikum Nürnberg Nord	Nürnberg
Germany	Harzklinikum Dorothea Christiane Erxleben GmbH	Quedlinburg
Germany	Universitätsklinikum Regensburg	Regensburg
Germany	HELIOS Kliniken Schwerin	Schwerin
Germany	Universitätsklinikum Tübingen	Tübingen
Germany	Universitätsklinikum Ulm	Ulm

Sponsors (1)

Lead Sponsor	Collaborator
EuMelaReg gGmbH

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Median time on treatment	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	Permanent study drug discontinuation due to any reason	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
Secondary	Permanent study drug discontinuation due to adverse drug reactions	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
Secondary	Pyrexia and related symptoms	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
Secondary	Adverse drug reaction management: pyrexia	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
Secondary	Adverse drug reactions in Follow-up	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
Secondary	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).	Over the course of treatment plus 3 months safety follow up, assessed up to 15 months
Secondary	Relapse free survival	Relapse free survival (RFS) time and rate	From date of first treatment until the date of treatment end, assessed up to 12 months
Secondary	Distant metastasis free survival time	Distant metastasis free survival (DMFS) time.	From date of first treatment until the date of treatment end, assessed up to 12 months
Secondary	Distant metastasis free survival rate	Distant metastasis free survival (DMFS) rate.	From date of first treatment until the date of treatment end, assessed up to 12 months
Secondary	Overall survival time	Overall survival (OS) time.	From date of first treatment until the date of treatment end, assessed up to 12 months
Secondary	Overall survival rate	Overall survival (OS) rate.	From date of first treatment until the date of treatment end, assessed up to 12 months
Secondary	Time on treatment and efficacy endpoints	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