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

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ClinicalTrials.gov Identifier: NCT03944356
Recruitment Status : Not yet recruiting
First Posted : May 9, 2019
Last Update Posted : July 5, 2019
Sponsor:
Information provided by (Responsible Party):
EuMelaReg gGmbH

Study Description
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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.


Condition or disease Intervention/treatment
Melanoma Drug: Dabrafenib and Trametinib

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
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Study Type : Observational
Estimated Enrollment : 250 participants
Observational Model: Case-Only
Time Perspective: Prospective
Official Title: BRAF-/MEK-Inhibition With Dabrafenib and Trametinib in Melanoma Patients in the Adjuvant Setting: a Non-interventional Observatory Study
Estimated Study Start Date : July 2019
Estimated Primary Completion Date : June 2021
Estimated Study Completion Date : December 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Melanoma

Groups and Cohorts
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Intervention Details:
  • Drug: Dabrafenib and Trametinib
    Dabrafenib and trametinib treatment under routine conditions according to the applying SmPC.
    Other Name: Tafinlar and Mekinist

Outcome Measures
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Primary Outcome Measures :
  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 Outcome Measures :
  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).


Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
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.
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
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03944356


Locations
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Germany
Elbe Kliniken Stade - Buxtehude GmbH
Buxtehude, Niedersachsen, Germany, 21614
Contact: Peter Mohr, Dr.    +49 41617036217    Peter.Mohr@elbekliniken.de   
Universitätsklinikum Essen, Klinik und Poliklinik für Dermatologie, Venerologie und Allergologie
Essen, Nordrhein-Westfalen, Germany, 45147
Contact: Dirk Schadendorf, Prof. Dr.         
Universitätsklinik Kiel, Klinik für Dermatologie, Venerologie und Allergologie
Kiel, Schleswig-Holstein, Germany, 24105
Contact: Micheal Weichenthal, Prof. Dr.         
Sponsors and Collaborators
EuMelaReg gGmbH
More Information
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Responsible Party: EuMelaReg gGmbH
ClinicalTrials.gov Identifier: NCT03944356    
Other Study ID Numbers: EUMR-18001
First Posted: May 9, 2019    Key Record Dates
Last Update Posted: July 5, 2019
Last Verified: April 2019
Additional relevant MeSH terms:
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Melanoma
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
 Nevi and Melanomas
Trametinib
Dabrafenib
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action