Biomarker-driven Therapy for Melanoma

Study Overview
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Brief Summary
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Patients included will undergo biopsy and the molecular analysis will be discussed at the institutional molecular tumor board. The recommandation of the molecular tumor board will be provided to the physician in charge of the patient for final treatment desicion. The main endpoints are the number of patients with actionable molecular alterations, the number of patients with a treatment recommendation, the number of patients receiving the recommended therapy, overall survival of the patients treated according to recommendations or not. For patients treated according to the recommendations: Response rate and progression free survival at 6 months according to RECIST criteria.

Detailed Description
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Eligible patients have to have a histologically proven metastatic melanoma failing standard treatments. Other inclusion criteria included age ≥ 18 years; Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-2; life expectancy ≥ 24weeks; adequate renal, liver, and bone marrow functions. Previous therapy with intravenous chemotherapy, immunotherapy or major surgery at least 4 weeks before inclusion was allowed. Patients were excluded if they had a history of cardiac disease or metastatic brain or meningeal tumors. The study is approved by the institutional research ethics board. Molecular analysis is performed at the Max Planck Institute for Molecular Genetics Berlin and a comprehensive report is made available with 4-8 weeks. The molecular tumor board interprets the data and transforms them into treatment recommendations by identifying and prioritizing predictive biomarkers. The recommendations rely on the definition of evidence levels attributed to every single aberration and the interdisciplinary discussion of the aberrations with regard to patient situation, availability of drugs, and clinical trials. The recommendations are transmitted to the physician in charge of the patient for the final decision to treat or not the patient accordingly. The main endpoints are the number of patients with actionable molecular alterations, the number of patients with a treatment recommendation, the number of patients receiving the recommended therapy, overall survival of patients treated according to recommendations or not. For patients treated according to the recommendations: Response rate and progression free survival at 6 months according to RECIST criteria.

Official Title
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Feasibility Study of Biomarker-driven Therapy Based on a Comprehensive Molecular Analysis of Tumor Tissue and Blood Collections in Melanoma

Conditions
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Melanoma

Intervention / Treatment
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* Drug: Molecular guided therapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: histologically proven metastatic melanoma failing standard treatments age ≥ 18 years Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-2 life expectancy ≥ 24 weeks adequate renal, liver, and bone marrow functions Exclusion Criteria: - history of cardiac disease or metastatic brain or meningeal tumors

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: Basic Science
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Molecular guided therapy<br> | Drug: Molecular guided therapy<br>* Biomarker-driven therapy according to recommandations of the precision oncology tumor board including MEK Inhibitors (Trametinib 2 mg/d, Selumetinib 75 mg 2/d), MET Inhibitors (Crizotinib 250 mg 2/d, or Cabozantinib 60mg/d), RAS Inhibitor (Sorafenib 400 mg 2/d), Cell cycle Inhibitor (Palbociclib 125 mg/d) and Checkpoint Inhibitor (Nivolumab 240 mg every 2 weeks).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Feasibility (actionable molecular alterations) | number of patients with actionable molecular alterations | Through study completion over 5 years | 
| Feasibility (number of patients with a treatment recommendation) | number of patients with a treatment recommendation | Through study completion over 5 years | 
| Feasibility (number of patients receiving the recommended therapy) | number of patients receiving the recommended therapy | Through study completion over 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival | Overall survival | 5 years | 
| Response rate | Response rate of the patients treated according to the recommendations | 1 year | 
| Progression free survival at 6 months according to RECIST criteria | PFS according to RECIST criteria for the patients treated according to the recommendations | up to 6 months |