Active clinical trials for "Melanoma"

With a high incidence, low survival rates and limiter availability of effective treatment, melanoma is one of the research priorities for health authorities. Optimizing the development of both academic and private research requires the availability information on the features of patients. To meet this need, the French Multidisciplinary Melanoma Group (GMFMel) in collaboration with INCa (French National Cancer Institute), the CeNGEPS (National Centre for Healthcare Products Trial Management) and the CIC-BT0503 from Nantes University Hospital (Biotherapy Clinical Centre of Investigation) has set up in April 2011 a Clinical Investigation Network for melanoma, called the CeNGEPS-GMFMel network. Nowadays, the network is named : RIC-Mel : network for Research and Clinical Investigation on Melanoma. Aims of the network are to promote translational and epidemiological projects as well as to optimize the achievements of clinical trials. To achieve these goals, a database was launched in 2012 that gives a permanently updates mapping of melanoma treated in France with the key information needed for any research projects.

Melanoma is the most aggressive skin cancer. Major advances in metastatic melanoma treatment emerge from new immunotherapies that target specific immune inhibitory checkpoint receptors, mainly PD1 and CTLA-4, and overcome the exhaustion state of T cells. In this context, checkpoint inhibitors, such as Ipilimumab (anti-CTLA-4 monoclonal antibodies, mAb) and Nivolumab or Pembrolizumab (anti-PD1 mAb), have demonstrated survival benefit in advanced melanoma patients. Anti-PD1 agents and combination of anti-PD1 and anti CTLA-4 have now been approved as first line therapy in melanoma. However, the predictive factors of response to these immunotherapies remain so far elusive. Recent studies provided consistent evidence that the immune infiltration could be tested as a biomarker for such immunotherapies. Moreover, the very recent concept of tumor neoantigens as biomarkers of response to anti-CTLA-4 mAb, and potentially also to anti-PD1 or combination therapies, is promising but needs to be further explored. In this context, the aim of our program is to identify and validate an immune signature predictive of anti-PD-1 benefit in the treatment of advanced melanoma patients. To this aim, tumor samples from 120 melanoma patients enrolled prospectively, treated with anti-PD1 mAb alone or combined with anti CTLA4, will be collected as well as the corresponding peripheral blood mononuclear cells (PBMC). Tumor infiltration with immune cells will be characterized on paraffin embedded melanoma samples. The investigators will also perform whole-exome sequencing on tumors and matched PBMC samples. Our primary objective is to develop a combined immuno-signature based on an immuno-score (CD3, CD8, CD45RO…) to quantify the in situ immune populations with a dedicated image analysis system combined with the simultaneous detection of CD8-PD-1 and PD-L1 by immunofluorescence in baseline tumor samples. This will permit to predict 1-year survival of patients with advanced melanoma treated with anti-PD1 and transfer in patient's care. Our secondary objectives are: 1/ To assess the interest of the detection of tissue-resident memory (TRM) T cells (CD8-CD103) as a predictive biomarker of response and survival at 1-year; 2/ To extend the panel of neoantigens published by Snyder et al to other neoantigens using a next-generation sequencing (NGS) approach on tumor samples obtained before therapy; 3/ To establish the prognostic value of this panel of neoantigens to predict tumor response to anti-PD1 and 1-year survival; 4/ To functionally validate the identified tumor neoantigens by stimulating patient PBMC with neoantigen peptides and measuring tumor-specific T-cell reactivity; 5/ To define the best marker and/or the best combination of markers predicting the overall response rate and the survival at 12 and 18 months; 6/ To attempt to establish a correlation between immuno-signature and neoepitopes and 7/ To transfer this immune signature in routine basis if validated. Thus, our project will integrate two complementary strategies to define a robust and reliable score system for predicting anti-PD1 targeting immunotherapy response. This study will provide a unique opportunity to validate various putative biomarkers in an integrated way that could help in determining the respective value of each isolated parameter and potentially lead to the definition of a composite biomarker. The identified immune signature would be of major interest in the field of cancer immunotherapy in order to select and manage patient treatment, and to consider the benefice or toxicities expected. It will also help to identify new target antigens of effective antitumoral immune responses and to understand the resistance mechanisms established by the tumor and its influence on the response to current immunotherapies.

SPECTAmel is a standardized, quality-assured molecular screening platform for tumor characterization and storage of human biological material (HBM) for the purpose of integrating new biomarkers into clinical trials and optimizing access of patients to therapeutic biomarker-driven clinical trials. HBM and clinical/pathological data are collected from consenting patients.

This study seeks to correlate microbial sequencing data from a punch biopsy in patients with skin cancer both melanoma and non-melanoma.

The study will test the usefulness of a contrast agent to help image tumors in the eye. In this study, patients with eye melanoma who are going to have their eye removed, will have their eye imaged by ultrasound (sound waves) before and after intravenous injection of microbubbles. The pathology characteristics of the tumor in the removed eye will be compared with the images.

This study has two ultimate goals: Understand how the original melanoma from the skin spreads to the CNS. In order to study this we need to collect (and compare) the original skin melanoma, the CNS melanoma, as well as any other melanoma that has not metastasized to the CNS. Develop a diagnostic blood test that will early identify subjects at high risk for developing CNS metastasis or patients who may already have CNS metastasis but the MRI or the CAT scan cannot yet detect it. Thus, the investigators plan to collect CSF from subjects like you who have melanoma CNS metastases in order to confirm the presence of this biomarker.

Up to half of patients with ocular melanoma (also called iris, choroidal or uveal melanoma) develop metastasis. We have found that certain molecular features of the eye tumor can be detected by gene expression profiling and accurately predict which patients will develop metastasis. This molecular test could eventually allow high risk patients to receive preventative therapy to delay or prevent the development of metastasis. The goal of this study is to prospectively validate the predictive accuracy of the gene expression-based molecular test and compare it to monosomy 3, the most common but potentially less accurate molecular marker for metastasis in ocular melanoma.

This is an open label, multi-center expanded access treatment protocol evaluating lifileucel (LN-144) in patients with unresectable or metastatic melanoma.

This is a single arm open label, multicenter, non randomized, access study of trametinib for subjects with histologically confirmed cutaneous melanoma with a BRAF V600E/K positive mutation that is either advanced unresectable (stage IIIc) or distant metastatic (stage IV). Trametinib may be given as monotherapy or in combination since first line metastatic melanoma as per inclusion criteria. Subjects who received prior BRAF inhibitor may be included if they have not progressed under such treatment or if they have presented limited progression as per eligibility criteria. It is estimated that between 250 and 400 subjects with histologically confirmed cutaneous melanoma with a BRAF V600E/K positive mutation that is either advanced unresectable (stage IIIc) or distant metastatic (stage IV) will be enrolled.

This is an expanded access program (EAP) for patient with Melanoma and Glioblastoma who have progressed after prior Protocol therapy including Bevacizumab, Temozolomide ( TMZ ), Ipilimumab, BRAF and MEK inhibitors. The patients whose tumors are EGFR, MET or ALK positive should first receive an EFGR or ALK inhibitor, respectively, prior to treatment with pembrolizumab.