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NCT Number: NCT03944356

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

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.

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Key information

Conditions

Melanoma Neoplasms Neoplasms by Histologic Type Neoplasms by Site Neoplasms, Germ Cell and Embryonal Neoplasms, Nerve Tissue Neuroectodermal Tumors Neuroendocrine Tumors Nevi and Melanomas Skin Diseases Skin Neoplasms Skin and Connective Tissue Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Observational

Primary location

Elbe Kliniken Stade - Buxtehude GmbH, Buxtehude, Lower Saxony, Germany

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About this study

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.

Who can participate

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Dabrafenib and Trametinib

Drug

Dabrafenib and trametinib treatment under routine conditions according to the applying SmPC.

Other names: Tafinlar and Mekinist

Primary outcomes

  1. 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.

Secondary outcomes

  1. 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.

  2. 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).

  3. 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.

  4. 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.

  5. 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.

  6. 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).

  7. 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

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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).

Sponsors and collaborators

Lead sponsor

EuMelaReg gGmbH

Industry

Registry information

Official study title

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

Acronym: Combi-EU

Important dates

Study start
2019
Primary completion
2023
Study completion
2024
First posted
May 9, 2019
Registry last updated
Mar 12, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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