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

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ClinicalTrials.gov Identifier: NCT01543113
Recruitment Status : Completed
First Posted : March 2, 2012
Last Update Posted : February 24, 2014
Sponsor:
Collaborator:
QIAGEN Gaithersburg, Inc
Information provided by (Responsible Party):
Rennes University Hospital

February 21, 2012
March 2, 2012
February 24, 2014
January 2011
March 2012   (Final data collection date for primary outcome measure)
c-Kit exons 11, 13, 17 and 18 will be sequenced (direct sequencing and pyrosequencing when possible) [ Time Frame: Day 1 ]
c-Kit exons 11, 13, 17 and 18 will be sequenced (direct sequencing and pyrosequencing when possible)
Same as current
Complete list of historical versions of study NCT01543113 on ClinicalTrials.gov Archive Site
  • level of c-Kit determined by immunohistochemistry [ Time Frame: Day 1 ]
    level of c-Kit determined by immunohistochemistry
  • 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). [ Time Frame: Day 1 ]
    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).
Same as current
Not Provided
Not Provided
 
cKIT, BRAF/NRAS Mutations in Advanced Melanoma : Clinical Outcome in Response to Tyrosine-kinase Inhibitors - KitMel Project
cKIT, BRAF/NRAS Mutations in Advanced Melanoma : Clinical Outcome in Response to Tyrosine-kinase Inhibitors - KitMel Project

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.

Not Provided
Interventional
Not Applicable
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Diagnostic
Melanoma
Other: sequencing
sequencing
melanoma
melanoma
Intervention: Other: sequencing
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
288
250
February 2014
March 2012   (Final data collection date for primary outcome measure)

Inclusion Criteria:

  • melanoma
  • white caucasian population
Sexes Eligible for Study: All
Child, Adult, Older Adult
No
Contact information is only displayed when the study is recruiting subjects
France
 
 
NCT01543113
LOC/10-16 - KitMel
2010-A01310-39 ( Other Identifier: AFSSAPS )
10/43-785 ( Other Identifier: CPP Ouest V (Rennes) )
11.272 ( Other Identifier: CCTIRS )
911305 ( Other Identifier: CNIL )
No
Not Provided
Not Provided
Rennes University Hospital
Rennes University Hospital
QIAGEN Gaithersburg, Inc
Principal Investigator: Marie-Dominique Galibert, PU-PH Rennes University Hospital
Rennes University Hospital
February 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP