Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Symptoms and General Pathology

Diseases and Abnormalities at or Before Birth

Rare Diseases

Melanoma

Nevus, Pigmented

Nevus

Syndrome

Dysplastic Nevus Syndrome

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Nerve Tissue

Nevi and Melanomas

Skin Neoplasms

Skin Diseases

Neoplastic Syndromes, Hereditary

Genetic Diseases, Inborn

Neuroendocrine Tumor

Neuroepithelioma

Melanoma-prone families from dermatology clinics.

Maria T Landi, M.D.

During the course of a case-control study of melanoma conducted at the Bufalini Hospital, Cesena, Italy in the years 1994-1996, 20 families with 2 or 3 melanoma cases were identified and studied. The area where the study was conducted showed the steepest increase in melanoma incidence in Mediterranean populations between the years 1987 and 1997.

Clinical characteristics of melanoma in the families studied were similar to those typically described in fair-skinned populations, but no relevant mutations in the coding regions of known candidate genes from melanoma have been found. Lack of findings could be due to the modest number of families and the small number of affected CMM cases examined. We cannot exclude the possibility of alterations in introns, splicing sites or promoter regions. Also epigenetic factors could affect the expression of the gene products we studied. Alternatively, germline alterations of a gene(s) other than the candidate genes we analyzed may play an important role in melanoma predisposition in this population. A large number of families is needed to test these hypotheses.

These additional families could provide an important contribution to the understanding o melanoma development. In fact, this population does not generally have the host characteristics that are usually associated with higher risk for melanoma (e.g., light skin color, red hair, blue eyes, multiple freckles, tendency to sunburn, etc.) but do have a relative high frequency of dysplastic nevi and melanoma.

The main objective of this study is to recruit more families at the Bufalini Hospital, Cesena, Italy in order to reach a larger sample size. Recently, 16 potential melanoma-prone families have been identified through patient's or physicians' referrals by the Dermatologists at the Bufalini Hospital. The dermatologists have maintained close relationships with members of these families and are confident that these subjects would be willing to participate in a study if contacted. The first goal of our study is to contact this family group and verify their willingness to participate in the study. In addition, new families could be identified and recruited.

We propose to conduct a pilot project. We estimate recruitment of approximately 25 families with 2 or more melanoma cases in first -degree relatives over a one-year period, including the 16 families already identified and approximately 10 new kindreds. At the end of the pilot phase we will determine the feasibility of continuing recruitment.

To date 557 subjects, including cases of melanoma and unaffected relatives, have been recruited in the family study of melanoma at the Bufalini Hospital, Cesena, Italy, University ofl'Aquila, L'Aquila, Italy, and the Istituto Valenciano de Oncologia, Valencia, Spain. Clinical characteristics of melanoma in the families studied were similar to those typically described in fair-skinned populations.

In the original study from the Bufalini Hospital, only 7% of the families analyzed have been shown to carry mutation in the CDKN2A gene, known candidate gene for melanoma, and no other mutation in additional susceptibility genes have been identified. The possibility of alterations in introns, splicing sites, or promoter regions cannot be excluded. Also, epigenetic factors could affect the expression of the gene products we studied. Alternatively, germline alterations of a gene(s) other than the candidate genes may play an important role in melanoma predisposition in this population. We began genome-wide scanning of the first 47 families. There was no evidence for linkage to either chromosome 9 or chromosome 1, previously shown to be susceptibility loci for melanoma. We extended the samples size also including melanoma-prone families from other Italian investigators. We have performed fine mapping of the loci that appeared interesting in the first linkage analysis. We did not confirm the previous association with the disease and published a manuscript to report the null results. Some of these families were also analyzed together with other families worldwide in linkage and genome-wide association studies with the goal of identifying loci potentially important for melanoma etiology. Moreover, some individuals from this study are being analyzed for presence of variants in susceptibility genes in pigmentation, DNA repair, and other pathways together with the melanoma samples from the case-control study (02-C- N(35). Finally, some families with three or more affected individuals are ongoing exomic sequencing with the goal of identifying novel loci associated with melanoma susceptibility. More than 100 subjects have been sequenced to date. We have identified a potentially important candidate gene for melanoma and are investigating additional families and melanoma cases to verify whether we can replicate this finding.

This protocol proposes to continue recruitment of families in order to reach a larger sample size for future analysis. The additional families could provide an important contribution to the understanding of melanoma development.

In addition, this protocol proposes to continue recruiting subjects for the tissue study subgroup at the Bufalini Hospital of Cesena, the Unviersity of I' Aquila, Italy and the Istituto Valenciano de Oncologia, Valencia, Spain. To date, 98 subjects have been enrolled in this study. The study aims at investigating the progression from nevi to melanoma in a cross sectional study of melanoma cases. The tissue study component focuses on the comparison of gene expression, somatic mutations, genetic variants, and proteomics profile in normal skin, common melanocytic nevi, dysplastic nevi, and melanoma tissue samples from the same individuals (familial or sporadic cases). Each subject completes an interview based questionnaire on sun exposure, pigmentation, sunsensitivity, family and medical history, and other melanoma risk factors and donates a blood sample.

whole blood, lymphocytes, tissue sections, plasma

Family Study of Melanoma in Italy

National Cancer Institute (NCI)

Neoplasm Metastasis

Melanoma, Cutaneous Malignant

Falk G Bechara, PD Dr.

MicroRNAs (miRNAs) are very small endogenous RNA molecules about 22-25 nucleotides in length, capable of post-transcriptional gene regulation. miRNAs bind to their target messenger RNAs (mRNAs), leading to cleavage or suppression of target mRNA translation based on the degree of complementarity. miRNAs have recently been shown to play pivotal roles in diverse developmental and cellular processes and linked to a variety of skin diseases and cancers. In the present study, the investigators examines the expression profiles of miRNA machinery components such as miRNA maturation and transport factors, microprocessor complex and RISC subunits in cutaneous melanoma, cutaneous melanoma metastases and benign melanocytic nevi.

Patients with cutaneous melanoma, cutaneous melanoma metastases and benign melanocytic nevi were included in the study. Punch biopsies were harvested from the center of the tumors. The miRNA machinery components were detected by quantitative real-time reverse transcriptase polymerase chain reaction.

miRNA Machinery in Melanoma, Melanoma Metastases and Benign Melanocytic Naevi

The miRNA Machinery in Melanoma, Melanoma Metastases and Benign Melanocytic Naevi

Ruhr University of Bochum

Postdoc

Anti-Infective Agents

All Drugs and Chemicals

Carbamide Peroxide

Benign nevi dermoscopically sub-classified into 4 dermoscopic types (i.e., with globular, reticular, mixed pattern with globules in the center and mixed pattern with globules at the periphery) were excised from healthy volunteers for further genetical analysis

Benign nevi excised for the study purpose where genetically analyzed for the presence/absence of BRAF and NRAS mutations

To test the frequency of BRAF and NRAS mutations among nevi

Iris Zalaudek, MD

This project is a multicenter study in which we will investigate a dual concept of nevogenesis. Study location is the Department of Dermatology at the Medical University of Graz in collaboration with centers in Austria (Vienna), Italy (Naples, Benevento, Modena), Spain (Barcelona) and the United States (New York).

The hypothesis is that small congenital melanocytic nevi (CMN), "early" acquired melanocytic nevi in childhood (AMN) and dermal nevi, all dermatoscopically characterized by globular pattern, belong to the same spectrum of genetically determined melanocytic proliferations that develop due to endogenous pathways, in contrast to "true" acquired melanocytic nevi, dermatoscopically showing reticular pattern, that develop due to exogeneous factors such as UV-exposure.

The investigations to this study will verify whether small CMN, "early" AMN and dermal nevi, characterized by globular pattern differ in their genetic alterations compared to reticular typed nevi. It will be expected that globular typed nevi and eventually dermal nevi lack B-RAF mutations whereas reticular nevi show alterations in the B-RAF gene. Study location: Graz

Study to Test Genetic Alterations Among Different Dermoscopic Types of Melanocytic Nevi.

BRAF and Nevi.Nevi Are Common Benign Pigmented Tumors of the Skin. Mutations in So-called BRAF and NRAS Genes Genes Appear to be Initiating Events Responsible for the Formation of Nevi.

All nevi were analyzed for BRAF mutations using the (less sensitive) Sanger method. A random subset of nevi was also analyzed using the (more sensitive) Ultradeep pyro-sequencing method (UDPS). The frequency is reported here as the number of BRAF mutations found by each method.

All nevi were analyzed for NRAS mutations using the (less sensitive) Sanger method. The (more sensitive) Ultradeep pyro-sequencing method (UDPS) is not applicable for this mutation. The frequency is reported here as the number of NRAS mutations from the analyzed nevi.

Medical University of Graz

Department of Dermatology, Medical University of Graz Austria

postoperative complications were not collected or assessed

Nevi

Age, Categorical

Age Continuous

Sex: Female, Male

Austria

Italy

Region of Enrollment

During first year of enrollment too few patients agreed to participate. Therefore a sample of 21 nevi were additionally retrospectively included.

Prof. Dr. Iris Zalaudek

Sanger method (n=45)

UDPS (n=24)

Frequency of BRAF Mutations Among Nevi

Frequency of NRAS Mutations Among Nevi

Overall Study

Ocular Melanoma

Intraocular Melanoma

Antineoplastic Agents

Amino Acids

Vaccines

Poly ICLC

Immunologic Factors

Interferons

Histidine

6MHP (200mcg of each peptide) and 300mcg of NeoAg-mBRAF will be co-administered locally with 0.9mg of polyICLC and CDX-1140. There will be a dose escalation of CDX-1140 (50mcg, 200mcg, 800mcg, 3.0mg). A vaccine containing all of these components will be given on days 1, 22, 43, and 64. The vaccine will be given subcutaneously/intradermally.

6 melanoma helper vaccine comprised of 6 class II MHC-restricted helper peptides

6MHP

BRAF 586-614 (V600E) peptide to which a histidine has been added to the N-terminus, resulting in BRAF 585-614 (V600E).

NeoAg-mBRAF

PolyICLC

CDX-1140

Craig L. Slingluff, Jr., MD

This study evaluates whether it is safe to administer a peptide vaccine made of 6MHP and a mutated neoantigen peptide (BRAF585-614-V600E) combined with adjuvants. The adjuvants that will be used in this trial are a CD40 antibody (CDX-1140) and a toll-like receptor (TLR) 3 agonist (Poly-ICLC). The study will also investigate the effects of the vaccine and the adjuvants on the immune response. The investigators will monitor these effects by performing tests in the laboratory on participants' blood and skin tissue.

Melanoma Vaccine Against Neoantigen and Shared Antigens by CD40 Activation and TLR Agonists In Patients With Melanoma (Including Ocular Melanoma)

Enhanced Melanoma Vaccine Against Neoantigen and Shared Antigens by CD40 Activation and TLR Agonists in Patients With Melanoma

Number of participants with dose-limiting toxicities based on CTCAE v5.0

Number of participants with durable or persistent CD4+ Th1 responses to the melanoma vaccine at either day 85 or day 176, or both

Number of FoxP3+ CD4+ T cells per mm\^2 in vaccine site biopsies

Number of participants with circulating Tregs (CD4+ FoxP3+) as a proportion of circulating CD4 T cells

Number of participants with CD4+ T cell response; maximum increase after vaccination at any time point.

Number of participants with CD4+ T cell response to the melanoma peptides

Celldex Therapeutics

Craig L Slingluff, Jr

Professor of Surgery; Director, Human Immune Therapy Center

PCPs randomized to the intervention group will receive the educational training program at the beginning of the study, extending over a maximum of five months.

PCPs randomized to the control group will have the option of receiving the educational training program at the end of the study.

The educational training program (intervention) consists of four sequential phases:

1. Knowledge Acquisition
2. Skills Assessment
3. Deliberate Practice
4. Clinical Proficiency

Educational training program

June K Robinson, MD

This is a four-phase educational intervention for primary care practitioners (PCPs) to perform opportunistic melanoma surveillance. Based on prior research, the investigator will develop an interactive melanoma early detection skills training program for PCPs according to the principals of mastery learning. The proposed educational intervention will improve practicing PCPs' knowledge, competence, confidence, and diagnostic performance regarding pigmented lesions and attitude concerning importance of skin surveillance. In addition, this research aims to examine the clinical proficiency of PCPs regarding pigmented lesions. The proposed educational intervention will reduce the percentage of benign lesions referred to dermatology.

Cutaneous melanoma is considered a potentially curable disease if detected early. Primary care physicians (PCPs) are well positioned to detect early melanomas by performing opportunistic melanoma surveillance on the at-risk population during physical examination. Opportunistic surveillance means physician performance of visual inspection of skin exposed during your physical examination focused on the presenting condition. Opportunistic surveillance requires skills in both visual inspection of the skin and with magnification of the skin by a hand-held device, a dermoscope. (This research aims to 1) develop an easily disseminated, interactive melanoma early detection skills training program for PCPs and to 2) to examine the clinical proficiency of PCPs regarding pigmented lesions.

The knowledge to be gained by PCPs is essential to the development and successful introduction of a method for physicians to learn how to perform opportunistic surveillance for melanoma. By evaluating means of encouraging and facilitating opportunistic surveillance for melanoma, an educational program may eventually be brought into widespread use in training PCPs.

In addition to a Pre-training Test and Post-training Test, each of the phases of the educational training program is described below:

1. Knowledge Acquisition The Knowledge Acquisition phase will be delivered via personal computer/tablet. It will take about one hour to complete. The one-hour course consists of case histories and videos in which the following are presented: 1) threshold rules of visual inspection, 2) benefit of magnification with dermoscopy to assist with diagnosis, and 3) demonstration of the 3-point checklist of dermoscopy.
2. Skills Assessment The Skills Assessment phase will be delivered via smartphone. The program may be intermittently accessed taking up to two weeks to complete. The PCP will be asked to review and make simulated management decisions on 20 case vignettes with clinical images of body surfaces and dermoscopy of individual lesions. Clinical practice will be simulated with the requirement that you make a decision to refer to dermatology or a decision that a referral is not needed. If a biopsy is performed in the case vignette, the pathology report will be provided, and the PCP will be asked the next step in the patient's care. Performance feedback will be provided.
3. Deliberate Practice The Deliberate Practice phase will be delivered via smartphone. It will take between 1-8 weeks to complete. The PCP will be asked to review additional cases with visual inspection and dermoscopy to improve aspects of your performance that have demonstrated weakness. Individual strengths and weaknesses will be assessed, and personalized feedback will be provided. After achieving competency with the simulated cases, the research staff will provide the PCP with a DermScope device (a smartphone fitted with a dermoscope) to use in the next phase.
4. Clinical Proficiency The Clinical Proficiency phase will take place in the clinical practice of the PCP over the course of 1-8 weeks. The PCP will be asked to use the DermScope to capture and transmit at least 12 lesions. Informed consent will be obtained from each patient prior to obtaining the non-identifying images. During image capture, each photograph is marked by the DermScope program with the date, time, and the clinical assessment form (CAF). The image will be transmitted to the teleconsultant (PI), who will assign a unique identification number to the image and the data. The PI will render an opinion within 72 hours regarding the need to refer the patient to dermatology or reassure the patient. The PCP will be asked to make a decision regarding the management of the patient and communicate this decision as needed to the patient.

Training Primary Care Physicians to Perform Melanoma Opportunistic Surveillance

The difference-in-difference (DID) approach will be used to test the hypothesis that the educational intervention improved knowledge, attitude concerning importance of skin exam, competence, confidence, and diagnostic performance. The difference-in-difference estimator compares outcomes between pre-tests and post-tests between PCPs who received the educational intervention and those who did not.

Each PCP will be the unit of observation. We will choose an appropriate functional form for each outcome.For each outcome, a DID estimator that is significant at p \< 0.05 will support the hypothesis that the educational intervention improved outcomes. This analysis will be repeated for each of the five outcomes. We will use the Bonferroni correction for multiple comparisons.

The difference-in-difference (DID) approach will be used to test the hypothesis that the intervention reduced referrals of benign lesions. The model will be estimated using a random effects logistic regression to account for clustering due to repeated measures for each PCP (about 8 referrals before randomization and another 8 after the intervention). A 95% confidence interval for the odds ratio of α3 that falls below one will support the hypothesis.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Family Study of Melanoma in Italy	NCT00339222	Melanoma Dysplastic Nevi Melanocytic Nev...		10 Years - 100 Years	National Institutes of Health Clinical Center (CC)
miRNA Machinery in Melanoma, Melanoma Metastases and Benign Melanocytic Naevi	NCT01444560	Cutaneous Melan... Nevi		1 Year -	Ruhr University of Bochum
Study to Test Genetic Alterations Among Different Dermoscopic Types of Melanocytic Nevi.	NCT00422448	Nevi	To test the fre...	9 Years - 80 Years	Medical University of Graz
Family Study of Melanoma in Italy	NCT00339222	Melanoma Dysplastic Nevi Melanocytic Nev...		10 Years - 100 Years	National Institutes of Health Clinical Center (CC)
Melanoma Vaccine Against Neoantigen and Shared Antigens by CD40 Activation and TLR Agonists In Patients With Melanoma (Including Ocular Melanoma)	NCT04364230	Melanoma Ocular Melanoma Uveal Melanoma	6MHP NeoAg-mBRAF PolyICLC CDX-1140	18 Years -	University of Virginia
Training Primary Care Physicians to Perform Melanoma Opportunistic Surveillance	NCT02385253	Melanoma Nevi Skin Moles	Educational tra...	18 Years -	Northwestern University
Family Study of Melanoma in Italy	NCT00339222	Melanoma Dysplastic Nevi Melanocytic Nev...		10 Years - 100 Years	National Institutes of Health Clinical Center (CC)
Melanoma Vaccine Against Neoantigen and Shared Antigens by CD40 Activation and TLR Agonists In Patients With Melanoma (Including Ocular Melanoma)	NCT04364230	Melanoma Ocular Melanoma Uveal Melanoma	6MHP NeoAg-mBRAF PolyICLC CDX-1140	18 Years -	University of Virginia

Spots Global Cancer Trial Database for nevi

Every month we try and update this database with for nevi cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for nevi

Every month we try and update this database with for nevi cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for nevi cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.