BRAF-/MEK-Inhibition With Dabrafenib and Trametinib in Melanoma Patients in the Adjuvant Setting: a Non-interventional Observatory Study
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 232
- 试验地点
- 36
- 主要终点
- Median time on treatment
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Observational
- 观察模型
- Case Only
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
结局指标
主要结局
Median time on treatment
时间窗: 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.
次要结局
- Distant metastasis free survival time(From date of first treatment until the date of treatment end, assessed up to 12 months)
- Overall survival time(From date of first treatment until the date of treatment end, assessed up to 12 months)
- Permanent study drug discontinuation due to any reason(From date of first treatment until the date of treatment end, assessed up to 12 months)
- Pyrexia and related symptoms(From date of first treatment until the date of treatment end, assessed up to 12 months)
- Adverse drug reaction management: pyrexia(From date of first treatment until the date of treatment end, assessed up to 12 months)
- Overall survival rate(From date of first treatment until the date of treatment end, assessed up to 12 months)
- Adverse drug reactions in Follow-up(From date of first treatment until the date of treatment end plus 3 months of follow-up, assessed up to 15 months)
- Health-related quality of life(Over the course of treatment plus 3 months safety follow up, assessed up to 15 months)
- Distant metastasis free survival rate(From date of first treatment until the date of treatment end, assessed up to 12 months)
- Time on treatment and efficacy endpoints(From date of first treatment until the date of treatment end, assessed up to 12 months)
- Permanent study drug discontinuation due to adverse drug reactions(From date of first treatment until the date of treatment end, assessed up to 12 months)
- Relapse free survival(From date of first treatment until the date of treatment end, assessed up to 12 months)