Real-life Pharmacological Monitoring of Encorafenib-Binimetinib in the Treatment of Metastatic Melanoma

NCT06774989 | Recruiting

• 2 other identifiers: APHP2408952024-A00842-45
• Study Type: observational
• Target: 66
• Locations: 1 country
• Sites: 1

Brief Summary

In recent years, the prognosis for BRAFV600E-mutant metastatic melanoma has been transformed with targeted therapies combining BRAF and MEK inhibitors (dabrafenib-trametinib and encorafenib-cobimetinib), which have improved progression-free survival and overall survival. However, adverse events are very frequent, and a significant proportion of patients progress secondarily. Several clinical studies have shown that inter-individual variability in plasma exposure to BRAF inhibitors (dabrafenib, vemurafenib) or MEK inhibitors (trametinib) may contribute in part to the occurrence of severe toxicities, and on the efficiency of the treatment. To our knowledge, no data are currently available on the exposure/toxicity relationship for encorafenib and binimetinib. The aim of this study is to assess the association between plasma exposure of encorafenib and binimetinib and the occurrence of dose-limiting toxicity during the first 3 months of treatment. Our secondary objectives are the identification of factors of variability in plasma exposure to encorafenib and binimetinib, the assessment of the exposure-response relationship to treatment (PFS, OS), the evaluation of the influence of the residual plasma concentration of checkpoint inhibiting antibodies (nivolumab, pembrolizumab, ipilimumab) in the first month on the occurrence of dose-limiting toxicity during treatment with encorafenib/binimetinib. Also, the investigators will study the relationship between the kinetics of circulating tumour DNA levels and plasma exposure to encorafenib and binimetinib. Finally, the investigators will assess compliance with treatment. All patients over the age of 18 receiving encorafenib-binimetib for BRAF-mutated metastatic or locally advanced non-operable melanoma, regardless of line, in our 5 centres, will be included. After the patient has been informed and informed that he or she does not wish to be included in the study, an additional blood test will be taken during follow-up visits to the HDJ or specific follow-up consultation for his or her metastatic melanoma, where blood sampling is already planned as part of the treatment, during 1 year. The tubes will be sent to the laboratories for analysis in the usual way as part of routine care. A self-questionnaire will be given to the patient at different follow-up visits. Research data, including clinical, biological and self-questionnaire data, will be collected in the study via a web interface (e-CRF). Follow-up of the population will follow the rhythm of visits scheduled as part of the usual care of patients with melanoma undergoing targeted therapy. the investigators plan a 1-year sampling period, and a 2-year clinical follow-up period for each patient from the time of inclusion. Finally, the investigators plan a period of 1 year to analyze the data and write the article. Statistical analysis will be carried out by the investigating team (R software).

Conditions

Melanoma (Skin)

Keywords

melanoma; targeted therapy; BRAF and MEK inhibitors; pharmacokinetics

Outcome Measures

Primary Outcomes (1)

• association between the plasma exposure of encorafenib and binimetinib and the occurrence of dose-limiting toxicity

  association between the plasma exposure of encorafenib and binimetinib and the occurrence of dose-limiting toxicity during the first 3 months of treatment

  3 months

Secondary Outcomes (1)

• plasma exposure to encorafenib

  Month 1, Month 2, Month 6, Month 9 and 1 year

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Adult patients with BRAFV600-mutated metastatic melanoma treated with encorafenib and binimetinib (any line of therapy).

You may qualify if:

• Adults ≥ 18 years of age
• Histologically confirmed advanced melanoma, stage III/stage IV inoperable (primary cutaneous, mucosal or unknown)
• Treatment with encorafenib and/or binimetinib, whatever the line of treatment, for curative purposes.
• Affiliated to a social security scheme or beneficiary of such a scheme
• informed and non-opposition collected.

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead

Study Sites (1)

Department of Oncology-Dermatology, Ambroise Paré Hospital - APHP

Boulogne-Billancourt, 92100, France

RECRUITING

MeSH Terms

Conditions

Melanoma; Hereditary Sensory and Autonomic Neuropathies

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases; Nervous System Malformations; Nervous System Diseases; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Polyneuropathies; Peripheral Nervous System Diseases; Neuromuscular Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Genetic Diseases, Inborn

Study Officials

• Elisa FUNCK-BRETANO, MD, PhD

  Department of Oncology-Dermatology, Ambroise Paré Hospital - APHP

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Elisa FUNCK-BRENTANO, MD, PhD

CONTACT

+ 33171167721; elisa.funck-brentano@aphp.fr

Sarah Bouchereau, MD

CONTACT

+ 33149094442; sarah.bouchereau@aphp.fr

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 3, 2024
• First Posted: January 14, 2025
• Study Start: January 2, 2025
• Primary Completion (Estimated): January 1, 2028
• Study Completion (Estimated): January 1, 2028
• Last Updated: March 18, 2025

Record last verified: 2025-03

Locations

FR (1)