Therapeutic Drug Monitoring of BRAF-mutated Advanced Melanoma

Study Overview
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Brief Summary
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BRAF V600-mutant metastatic melanoma are commonly treated using a combination of anti-BRAF and anti-MEK tyrosine kinase inhibitors (TKIs). The OPTIMEL trial aims to study the interest of therapeutic drug monitoring (TDM) of TKIs and circulating tumor DNA (ctDNA) detected in plasma of patients with metastatic melanoma for disease monitoring. 35 patients with metastatic melanoma and treated with dabrafenib and trametinib will be enrolled in this trial. Blood samples will be collected for the determination of TKIs concentration and ctDNA detection.

Official Title
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Therapeutic Drug Monitoring of Kinase Inhibitors and Study of Circulating Tumor DNA in Patients With Mutated BRAF Metastatic Cutaneous Melanoma and Treated With Anti-BRAF and Anti-MEK Kinase Inhibitors

Conditions
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Melanoma (Skin)

Intervention / Treatment
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* Other: Blood sampling


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men and women 18 years of age and older Histologic proven advanced skin melanoma (Stage IV or stage IIIc inoperable) with BRAF V600 mutation Patient who will treated with combined kinase inhibitors (dabrafenib + trametinib). Patient able to stand a blood collection of 20 mL Ability to provide an informed written consent form Patient must be affiliated to a social security system Patient's legal capacity to consent to study participation and to understand and comply with the requirements of the study. Exclusion Criteria: Patient with mucosal melanoma Patient with non-metastatic skin melanoma (All stages except stage IV and stage III C inoperable) Patient with another synchronous cancer, or within 3 years Patient with a contraindication to blood collection of 20 mL Patient deprived of liberty or under supervision Patient unable to receive kinase inhibitor therapy Patient treated with another combined kinase inhibitors than dabrafenib and trametinib Pregnant or breastfeeding women Patient (man or woman) of childbearing age who does not agree to use of contraceptive methods validated during the study

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Biological<br> | Other: Blood sampling<br>* 2x10 ml of patient peripherical blood will be collected at D0, D15, D30, D90, D180, D270 and with progression or at the end of the follow-up at the 12th month.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Link between the presence of circulating tumor DNA and plasma concentrations of kinase inhibitors n patient with advanced BRAF(V600) mutated melanoma | ctDNA in patient with advanced BRAF(V600) mutated melanoma is estimated by the ratio of the Ct of the sample to the control. Plasma concentrations of anti-BRAF and anti-MEK tyrosine kinase inhibitors are expressed in μg / mL | 1 day | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ctDNA, MAPK inhibition, BRAF(V600) mutated