Interest of Tumor Replicates in Avian Embryo to Model Therapeutic Effects of BRAFi/MEKi in BRAF Mutated Melanoma

Study Overview
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Brief Summary
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This is an interventional mono-centric study in patients with BRAF mutated metastatic melanoma treated with BRAF/MEK inhibitors. The aim of the study is to test the grafting of patient tumoral cells in avian embryo and develop a predictive in vivo model for patient treatment response.

Official Title
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Interest of Tumor Replicates in Avian Embryo to Model Therapeutic Effects of BRAF Inhibitors/MEK Inhibitors (BRAFi/MEKi) in BRAF Mutated Melanoma

Conditions
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Melanoma

Intervention / Treatment
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* Procedure: Skin biopsy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients aged ≥ 18 years Signed written informed consent Patient with BRAF V600 mutated metastatic or unresectable melanoma histologically confirmed BRAFi/MEKi treatment indication Patient with skin tumor (excluded face and skinfold) available for biopsy Measurable disease as defined by RECIST v1.1 criteria Patient affiliated to or a beneficiary of a social security category Exclusion Criteria: Ocular melanoma Medical, psychiatric, cognitive or other conditions that may compromise the patient's ability to understand the patient information, give informed consent, comply with the study protocol or complete the study Pregnant or nursing (lactating) women Patients protected by law

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Biopsy<br>Skin biopsy before BRAFi/MEKi treatment | Procedure: Skin biopsy<br>* 5mm skin metastasis or primary melanoma biopsy<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Grafted avian embryo development | Number of grafted embryo which develop tumor measurable by 3D microscopy | 2 days post graft | 
| Grafted avian embryo viability | Survival rate of grafted embryo | 2 days post graft | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| BRAFi/MEKi maximum toxic effect dose in avian embryo | Survival rate in avian embryo after treatment injections in different concentrations | 3 months post treatment administration | 
| BRAFi maximum toxic effect dose in avian embryon | Survival rate in avian embryo after treatment injections in different concentrations | 3 months post treatment administration | 
| MEKi maximum toxic effect dose in avian embryo | weight of avian embryo after treatment injections in different concentrations | 3 months post treatment administration | 
| BRAFi maximum toxic effect dose in avian embryo | Height of avian embryo after treatment injections in different concentrations | 3 months post treatment administration | 
| MEKi maximum toxic effect dose in avian embryo | Height of avian embryo after treatment injections in different concentrations | 3 months post treatment administration | 
| BRAFi maximum toxic effect dose in avian embryo | Presence of cardiac malformation in avian embryo after treatment injections in different concentrations | 3 months post treatment administration | 
| MEKi maximum toxic effect dose in avian embryo | Presence of cardiac malformation in avian embryo after treatment injections in different concentrations | 3 months post treatment administration | 
| BRAFi maximum toxic effect dose in avian embryo | Presence of craniofacial malformation in avian embryo after treatment injections in different concentrations | 3 months post treatment administration | 
| MEKi maximum toxic effect dose in avian embryo | Presence of craniofacial malformation in avian embryo after treatment injections in different concentrations | 3 months post treatment administration | 
| Patient treatment response | RECIST 1.1 response | 3 months post inclusion | 
| Embryo treatment response (tumor) | Embryo tumor volume obtained by confocal microscopy before treatment administration compared with tumor volume of non-treated embryo | 2 days post graft | 
| Embryo treatment response (metastasis) | Metastasis appearance | 2 days post graft | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Melanoma, Avian embryo