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

Melanoma Clinical Trial

— KitMel  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01543113
• Other study ID #: LOC/10-16 - KitMel
• Secondary ID: 2010-A01310-3910
• Status: Completed
• Phase: N/A
• Start date: January 2011
• Est. completion date: February 2014

Study information

• Verified date: May 2023
• Source: Rennes University Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 288
• Est. completion date: February 2014
• Est. primary completion date: March 2012
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

Inclusion Criteria:

• melanoma

• white caucasian population

Related Conditions & MeSH terms

• Melanoma

Intervention

Other:
• sequencing
sequencing

Locations

Country	Name	City	State
France	Centre Eugène Marquis	Rennes	Bretagne
France	Rennes University Hospital	Rennes	Bretagne

Sponsors (2)

Lead Sponsor	Collaborator
Rennes University Hospital	QIAGEN Gaithersburg, Inc

Country where clinical trial is conducted

France, 

References & Publications (1)

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 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	c-Kit exons 11, 13, 17 and 18 will be sequenced (direct sequencing and pyrosequencing when possible)	c-Kit exons 11, 13, 17 and 18 will be sequenced (direct sequencing and pyrosequencing when possible)	Day 1
Secondary	level of c-Kit determined by immunohistochemistry	level of c-Kit determined by immunohistochemistry	Day 1
Secondary	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).	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).	Day 1