cKIT, BRAF/NRAS Mutations in Advanced Melanoma : Clinical Outcome in Response to Tyrosine-kinase Inhibitors - KitMel Project

NCT ID: NCT01543113

Last Updated: 2023-05-24

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 288 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-01-31
• Study Completion Date: 2014-02-28

Brief Summary

Background: Metastatic melanoma has a devastating prognosis and is one of the top causes of cancer death in young patients. Until now, available therapies were few and unreliable, but recent understanding of melanomas' molecular pathways has improve their classification and new clinical strategies have been proposed.

Initial studies showed that B-Raf/N-Ras mutations (respectively V600E and Q61) are the most frequent alteration being present in 70 to 80% of melanomas, characterizing non Chronic Sun-induced Damage skins (CSD). These include Superficial Spreading Melanomas (SSM) and Nodular Melanomas (NM). Other studies showed that c-Kit mutations are presently the predominant activating mutation (20 - 40 %) in Acro-Lentiginous Melanomas (ALM), Mucous Melanomas (MM) and in melanomas arising on CSD skin. c-Kit mutation pattern is more complex with four exons being affected leading to different mutations, which incidence and biological impact are less documented.

BRAF/NRAS genetics alterations drive constantly cell growth, being thus attractive targets. Spectacular results have indeed been obtained with the BRAF inhibitor that targets the V600E BRAF-mutated form. Data from GIST disease revealed that the different c-Kit mutations modulate differently c-Kit function and the response to targeted therapies.

Because c-Kit targeted therapy is a critical clinical issue, the investigators aimed to identify the most frequent mutations present in our population to propose appropriate screening test and adapt the therapy.

Methods: 250 melanoma samples corresponding to an homogeneous white-Caucasian population (Brittany, France) will be screened. c-Kit exons 11, 13, 17 and 18 will be sequenced (direct sequencing and pyrosequencing when possible). c-Kit copy number will be quantified by q-PCR and level of c-Kit determined by immunohistochemistry (IHC, CD117). Samples will also be analyzed for B-Raf mutations in codon 464, 466, 469 and 600, and for N-Ras mutations in codon 12, 13 and 61 (Pyrosequencing).

Expected Results:

Taken together, the investigators anticipate that the present genetic analysis of the tumours from patients with advanced melanoma will first document the type and frequency of cKit mutations, will confirm or not that BRAF, NRAS and cKit mutations are mutually exclusive and document their repartition in the melanomas sub-types. Finally this study will clue researchers in to how well patients will respond to a therapy that targets the growth-promoting proteins BRAF/NRAS and cKIT.

Conditions

Melanoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: DIAGNOSTIC
• Blinding Strategy: NONE

Study Groups

melanoma

melanoma

Group Type: OTHER

sequencing

Intervention Type: OTHER

sequencing

Interventions

sequencing

sequencing

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• melanoma
• white caucasian population

• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

QIAGEN Gaithersburg, Inc

INDUSTRY

Sponsor Role: collaborator

Rennes University Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Marie-Dominique Galibert, PU-PH

Role: PRINCIPAL_INVESTIGATOR

Rennes University Hospital

Locations

Centre Eugène Marquis

Rennes, Brittany Region, France

Rennes University Hospital

Rennes, Brittany Region, France

Countries

France

References

Pracht M, Mogha A, Lespagnol A, Fautrel A, Mouchet N, Le Gall F, Paumier V, Lefeuvre-Plesse C, Rioux-Leclerc N, Mosser J, Oger E, Adamski H, Galibert MD, Lesimple T. Prognostic and predictive values of oncogenic BRAF, NRAS, c-KIT and MITF in cutaneous and mucous melanoma. J Eur Acad Dermatol Venereol. 2015 Aug;29(8):1530-8. doi: 10.1111/jdv.12910. Epub 2015 Jan 26.

Reference Type: RESULT

PMID: 25623140 (View on PubMed)

Other Identifiers

2010-A01310-39

Identifier Type: OTHER

Identifier Source: secondary_id

10/43-785

Identifier Type: OTHER

Identifier Source: secondary_id

11.272

Identifier Type: OTHER

Identifier Source: secondary_id

911305

Identifier Type: OTHER

Identifier Source: secondary_id

LOC/10-16 - KitMel

Identifier Type: -

Identifier Source: org_study_id