Therapeutic Drug Monitoring of BRAF-mutated Advanced Melanoma (OPTIMEL)

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

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.

Study Overview

• Status: Completed
• Conditions: Melanoma (Skin)
• Intervention / Treatment: Other: Blood sampling

• Study Type: Interventional
• Enrollment (Actual): 35
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Dijon, France, 21079
    • Centre Georges François Leclerc (CGFL)
  • Thionville, France, 57 100
    • Hopital de Mercy
  • Vandœuvre-lès-Nancy, France
    • Institut de Cancérologie de Lorraine (ICL)
  • Vandœuvre-lès-Nancy, France, 54 511
    • CHRU Nancy

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Biological	Other: Blood sampling; 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Institut de Cancérologie de Lorraine
• Investigators: Principal Investigator: Geoffrois Lionnel, MD, Institut de Cancerologie de Lorraine

Study record dates

Study Major Dates

• Study Start (Actual): April 27, 2018
• Primary Completion (Actual): June 17, 2022
• Study Completion (Actual): June 17, 2022

Study Registration Dates

• First Submitted: January 18, 2018
• First Submitted That Met QC Criteria: January 24, 2018
• First Posted (Actual): January 31, 2018

Study Record Updates

• Last Update Posted (Actual): August 4, 2023
• Last Update Submitted That Met QC Criteria: August 3, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: ctDNA; MAPK inhibition; BRAF(V600) mutated
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Nevi and Melanomas; Melanoma
• Other Study ID Numbers: 2018-A00469-46

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No