BRAF-/MEK-Inhibition With Dabrafenib and Trametinib in Melanoma Patients (Combi-EU)
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| ClinicalTrials.gov Identifier: NCT03944356 |
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Recruitment Status :
Recruiting
First Posted : May 9, 2019
Last Update Posted : February 4, 2021
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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 |
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 |
| 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 |
| Actual Study Start Date : | July 1, 2019 |
| Estimated Primary Completion Date : | May 2023 |
| Estimated Study Completion Date : | July 2023 |
- Drug: Dabrafenib and Trametinib
Dabrafenib and trametinib treatment under routine conditions according to the applying SmPC.Other Name: Tafinlar and Mekinist
- 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.
- 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.
- 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).
- 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.
- 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.
- 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.
- 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).
- 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
- 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.
- 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.
- 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.
- 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.
- 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).
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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 |
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
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
| Contact: Alexandra Hansen | +49 3037026901 | alexandra.hansen@eumelareg.org |
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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: | February 4, 2021 |
| Last Verified: | February 2021 |
| Studies a U.S. FDA-regulated Drug Product: | No |
| Studies a U.S. FDA-regulated Device Product: | No |
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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 |