Clinical Trials Logo

Clinical Trial Summary

Prospective evaluation of clinical outcomes in patients with resectable or metastatic BRAF+ melanoma treated with dabrafenib and trametinib in real practice


Clinical Trial Description

Rationale and background It is now accepted by the majority of experts in oncology that most effective and safe therapy options should be considered for first-line treatment, including adjuvant setting. As the routine administration of drugs including dosing, treatment interruptions, and early termination in clinical practice may vary from procedures used in clinical trials, post-authorization "real-world" data are important to quantify feasibility, acceptance, and practical considerations on prescription of targeted therapy with Dabrafenib+Trametinib. Therefore, it is of great interest for clinical and scientific communities to evaluate patient and treatment choice used in routine practice of Russian oncology centers. The aim of this study is to asses clinical outcomes of patient receiving Dab+Tram in different substages of resectable melanoma and different lines in metastatic melanoma., Additionally, it is of interest to gain insights into real world data regarding quality of life of melanoma patients treated with Dabrafenib and Trametinib in adjuvant or metastatic setting. Research question and objectives Primary objective The primary objective in the study is to estimate relapse-free survival (RFS) in melanoma patients in adjuvant settings and progression free survival (PFS) in melanoma patients in metastatic settings. Primary endpoints • The primary efficacy endpoint of the study is 12-month RFS rate, definded as the time form index date to the date of first documented relapse or death due to any cause. The primary efficacy endpoint of the study is 12-month PFS rate, defined as the time from the index date to the date of the first documented progression by investigator judgement or death due to any cause. If a patient has not had an event, PFS will be censored at the date of the last tumor assessment Secondary objectives - To describe patient populations receiving dabrafenib and trametinib for stage III resectable melanoma with respect to demographics and clinical characteristics at index date (baseline). - To describe patient populations receiving dabrafenib and trametinib for stage IV metastatic melanoma with respect to demographics and clinical characteristics at index date (baseline). - Evaluate retrospectively the sequence of therapy prior to initiating treatment with Dabrafenib and Trametinib. - Analyze prospectively treatment options following disease recurrence or progression on treatment with Dabrafenib and Trametinib. - Analyze proportion (%) of patients receiving adjuvant therapy with Dabrafenib and Trametinib for melanoma stage IIIA/IIIB/IIIC/IIID - Analyze proportion (%) of patients receiving Dabrafenib and Trametinib in 1L/2L/3L/later lines in metastatic settings. - Assess clinical outcomes (including treatment duration, treatment discontinuation rate) in melanoma patients treated with Dabrafenib and Trametinib in adjuvant settings in real-world practice. - Assess clinical outcomes in melanoma patients treated with Dabrafenib and Trametinib in metastatic settings (including median PFS, treatment duration, RR and) in real-world practice. - Assess safety of therapy of interest: rate of adverse events associated with the therapy, proportions of patients and reasons of dose adjustment on dabrafenib and trametinib, discontinuation rate and reasons of discontinuation in melanoma patients treated with Dabrafenib and Trametinib in adjuvant and metastatic in real-world practice. - Describe changes in patient-reported symptoms and quality of life (QoL) in melanoma patients treated with Dabrafenib and Trametinib in real-world setting. Study design Patients will attend study sites in accordance with routine clinical practice. It is assumed that visits will performed every 3-4 months, as it is stated by the current guidelines (1). Patients will undergo standard procedures and tests according to clinical guidelines and physician's judgement (1). Available data from routine clinical management of the patients will be collected in the course of visits to investigation site. The supposed duration of observation within the study is 1 year which corresponds to the requested duration of adjuvant therapy and is in line with the median PFS - 11.1 months according to the COMBI D/V trials' analysis for dabrafenib+trametinib therapy in the first line treatment of metastatic cutaneous melanoma with BRAF mutation (2). The enrollment period will continue for two years. Baseline assessments will include collection of patient demographic data, disease history, treatment history, laboratory data and physical examination results as assessed by clinicians and patient reported outcomes (PROs) for symptoms and QoL. Treatment history will include all pharmacological therapy, its duration, response duration, reason for discontinuation. QoL assessment is not a part of routine practice for some investigation sites, hence, QoL will be evaluated if it does not interfere routine practice. At each following visit (as indicated above, approximately each 3-4 months up to 1 year) available information on treatment status, response and progression, PROs, patient performance status and any relevant adverse occurrences will be collected. Setting and study population This study is planned as a prospective non-interventional multicenter study. This study is observational in nature and does not impose a therapy protocol, diagnostic/therapeutic interventions or a visit schedule. Patients with resectable or metastatic BRAF+ melanoma, in that treatment with dabrafenib and trametinib was initiated, either newly diagnosed or progressive during prior lines of therapy, will be included into the study. Initiation of dabrafenib+trametinib therapy will be considered an index event. Adult patients receiving dabrafenib and trametitnib for adjuvant or metastatic melanoma treatment will be enrolled into study. Variables All data will be collected in the course of prospective visits of patient to the clinical site according to routine practice. Demographic, disease and treatment-related variables will be collected in order to ensure completeness of data for endpoint analysis. Definitions of variables for analysis will be given in the relevant section of protocol. Data sources Medical records and other disease-related documents will be used in the study. Study size This study does not test any pre-defined statistical hypotheses therefore sample size and power calculation projections are not applicable. Since there is no formal hypothesis-testing, sample size for this study is based on the feasibility of enrolling the desired population during the enrolment period for this study. Data analysis This is an exploratory study and no comparative analysis is planned. Descriptive statistics will be tabulated for the demographic and clinical characteristics and outcome variables. In all cases, point estimates as well as the corresponding two-sided 95% CI will be presented. No missing value imputation will be performed. Kaplan-Meier method will be used for the analysis of time-to-event. Milestones Planned dates of study milestones: Concept approved: 29 April 2021 Final protocol approval: 30 June 2021 Start of data collection (FPFV): 30 September 2021 End of enrollment (LPFV): 30 September 2023 End of primary data collection (LPLV): 30 September 2024 Final report on study results: 30 April 2025 Publication of study results: 30 September 2025 ;


Study Design


Related Conditions & MeSH terms


NCT number NCT05171374
Study type Observational
Source MelanomaPRO, Russia
Contact Igor Samoylenko, MD
Phone +74993249024
Email i.samoylenko@ronc.ru
Status Recruiting
Phase
Start date September 30, 2021
Completion date September 30, 2024

See also
  Status Clinical Trial Phase
Recruiting NCT05094804 - A Study of OR2805, a Monoclonal Antibody Targeting CD163, Alone and in Combination With Anticancer Agents Phase 1/Phase 2
Completed NCT03979872 - Risk Information and Skin-cancer Education for Undergraduate Prevention N/A
Recruiting NCT04986748 - Using QPOP to Predict Treatment for Sarcomas and Melanomas
Enrolling by invitation NCT00068003 - Harvesting Cells for Experimental Cancer Treatments
Recruiting NCT05707286 - Pilot Study to Determine Pro-Inflammatory Cytokine Kinetics During Immune Checkpoint Inhibitor Therapy
Recruiting NCT05470283 - Phase I, Open-Label, Study of Tumor Infiltrating Lymphocytes Engineered With Membrane Bound IL15 Plus Acetazolamide in Adult Patients With Metastatic Melanoma Phase 1
Recruiting NCT05077137 - A Feasibility Study Utilizing Immune Recall to Increase Response to Checkpoint Therapy Phase 1
Active, not recruiting NCT02721459 - XL888 + Vemurafenib + Cobimetinib for Unresectable BRAF Mutated Stage III/IV Melanoma Phase 1
Active, not recruiting NCT00341939 - Retrospective Analysis of a Drug-Metabolizing Genotype in Cancer Patients and Correlation With Pharmacokinetic and Pharmacodynamics Data
Recruiting NCT05839912 - Excision of Lymph Node Trial (EXCILYNT) (Mel69) N/A
Recruiting NCT04971499 - A Study of Dapansutrile Plus Pembrolizumab in Patients With PD-1 Refractory Advanced Melanoma Phase 1/Phase 2
Recruiting NCT05060432 - Study of EOS-448 With Standard of Care and/or Investigational Therapies in Participants With Advanced Solid Tumors Phase 1/Phase 2
Recruiting NCT05263453 - HL-085+Vemurafenib to Treat Advanced Melanoma Patients With BRAF V600E/K Mutation Phase 2
Completed NCT03348891 - TNF in Melanoma Patients Treated With Immunotherapy N/A
Terminated NCT03399448 - NY-ESO-1-redirected CRISPR (TCRendo and PD1) Edited T Cells (NYCE T Cells) Phase 1
Completed NCT03171064 - Exercise as a Supportive Measure for Patients Undergoing Checkpoint-inhibitor Treatment Phase 2
Not yet recruiting NCT05539118 - Interferon-α1b Combined With Toripalimab and Anlotinib Hydrochloride in Advanced Unresectable Melanoma Phase 1/Phase 2
Withdrawn NCT02854488 - Yervoy Pregnancy Surveillance Study
Completed NCT00297895 - Multicenter Selective Lymphadenectomy Trial II (MSLT-II) N/A
Active, not recruiting NCT05103891 - Relative Bioavailability of Binimetinib 3 x 15 mg and 45 mg Formulations Phase 1