Detection of Plasmatic Cell-free BRAF and NRAS Mutations : a New Tool for Monitoring Patients With Metastatic Malignant Melanoma Treated With Targeted Therapies or Immunotherapy ( MALT ) (MALT)

Detection of Plasmatic Cell-free BRAF and NRAS Mutations: a New Tool for Monitoring Patients With Metastatic Malignant Melanoma Treated With Targeted Therapies or Immunotherapy ( MALT )

The main objective of this project is to perform a longitudinal monitoring of BRAF and NRAS cell-free DNA in a large cohort of metastatic melanomas patients before treatment and during the follow-up. Results will be compared with clinical data as imaging (based on RECIST criteria) and the activity of lactate dehydrogenase in serum (LDH).

Study Overview

• Status: Unknown
• Conditions: Malignant Melanoma Stage III; Malignant Melanoma Stage IV
• Intervention / Treatment: Biological: quantification of BRAF and NRAS mutation

Detailed Description

During a consultation of follow-up for an advanced malignant melanoma (stage IIIb or IIIC or IV), an investigator presents the study to the patient and give him the note of information and the informed consent.

The patient can benefit from a reflexion period of of 7 days.

In case of agreement, a first blood draw will take place before initiation of any treatment. Between D15 and D30 a second blood draw will be taken. Then a blood draw will be necessary every two months until recurrence or progression of the disease for a maximum of 22 months.

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

Contacts and Locations

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Patients in metastatic situation for a malignant melanoma inoperable stage IIIB or IIIC or stage IV
• In first line of treatment by a targeted therapy (only or in association) or immunotherapy
• Every histological types of cutaneous or mucous malignant melanoma (excepted choroid melanomas)
• The tumor must be mutates for BRAF or NRAS
• The mutation status must have been realized in the Laboratory Pathology Clinical and Experimental (LPCE) of the CHU de Nice analysis of the status on-site metastatic mutational and/or primitive tumor must
• Membership or beneficiary of the national insurance scheme

Exclusion Criteria:

• Histories of cancer or other synchronous cancer
• Pregnant, breast-feeding Women. A pregnancy test will be practiced to the women old enough to procreate.
• Vulnerable People: adults under guardianship, patients deprived of freedom, minor

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: Patient with malignant melanoma; Patient with advanced or metastatic malignant melanoma (stage IIIB inoperable or IIIC or stage IV) will have a first blood test before any treatment, then at day 15 or 30 after initiation of therapy, and every two months until recurrence or progression for a maximum of 22 months.	Biological: quantification of BRAF and NRAS mutation; Quantification of cell-free BRAF and NRAS mutations with digital PCR

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Quantify plasmatic BRAF and NRAS mutation determine by PCR digitale in µg/ml before treatment	Day 0
Study the longitudinal monitoring of cell-free the kinetics of the plasma mutation of BRAF and NRAS mutation in µg/ml and comparing them with imaging (based on RECIST criteria) and with the activity of the lactate dehydrogenase in serum ( LDH) in U/l .	Month 24

Secondary Outcome Measures

Outcome Measure	Time Frame
Compare the results obtained by PCR digitale from the cell-free with the results on FFPE tissue samples	Month 24
Identify genomic alterations and mutations of resistances in a restricted subgroup of patient by New Generation Sequencing analysis	Month 24

Collaborators and Investigators

• Sponsor: Centre Hospitalier Universitaire de Nice
• Investigators: Principal Investigator: Elodie LONG-MIRA, MD, Centre Hospitalier Universitaire de Nice

Publications and helpful links

General Publications

• de Vries E, Bray FI, Coebergh JW, Parkin DM. Changing epidemiology of malignant cutaneous melanoma in Europe 1953-1997: rising trends in incidence and mortality but recent stabilizations in western Europe and decreases in Scandinavia. Int J Cancer. 2003 Oct 20;107(1):119-26. doi: 10.1002/ijc.11360.
• Dhillon AS, Hagan S, Rath O, Kolch W. MAP kinase signalling pathways in cancer. Oncogene. 2007 May 14;26(22):3279-90. doi: 10.1038/sj.onc.1210421.
• Bahadoran P, Allegra M, Le Duff F, Long-Mira E, Hofman P, Giacchero D, Passeron T, Lacour JP, Ballotti R. Major clinical response to a BRAF inhibitor in a patient with a BRAF L597R-mutated melanoma. J Clin Oncol. 2013 Jul 1;31(19):e324-6. doi: 10.1200/JCO.2012.46.1061. Epub 2013 May 28. No abstract available.

Study record dates

Study Major Dates

• Study Start (Anticipated): April 1, 2018
• Primary Completion (Anticipated): April 1, 2022
• Study Completion (Anticipated): December 1, 2022

Study Registration Dates

• First Submitted: March 26, 2018
• First Submitted That Met QC Criteria: April 3, 2018
• First Posted (Actual): April 10, 2018

Study Record Updates

• Last Update Posted (Actual): April 12, 2018
• Last Update Submitted That Met QC Criteria: April 11, 2018
• Last Verified: March 1, 2018

More Information

Terms related to this study

• 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: 17-AOI-07

Drug and device information, study documents

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