Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Rare Diseases

Melanoma

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Nerve Tissue

Nevus, Pigmented

Nevus

Nevi and Melanomas

Skin Neoplasms

Skin Diseases

Neuroendocrine Tumor

Neuroepithelioma

Patients with resectable stage IIIB-D melanoma will have a lymph node core biopsy to confirm metastatic lesions, following standard procedures. Additionally, a portion of the tumor tissue will be preserved for biomarker analysis. Participants will then be instructed to submit fecal samples and complete a dietary questionnaire before receiving three doses of PD1 monotherapy, in accordance with the center\&#39;s routine practice, typically spanning 6-10 weeks. Between weeks 10 and 12, a radiological assessment of the response will be conducted. Following this, participants will undergo regional lymphadenectomy, and the pathological response will be evaluated. After surgery, patients will be placed on adjuvant therapy for 12 months as per routine practice of the center . Subsequently, they will be monitored for five years, adhering to the institution\&#39;s standard follow-up protocol.

Gut microbiota analysis

Igor V Samoylenko, MD

Angelina O Kuzmenko, MD

Igor V Samoylenko, MD, PhD

The goal of this observational study is to learn about if new biomarkers such as gut microbiota and molecular genetics melanoma features could predict clinical radiological and pathological response to neoadjuvant monotherapy with anti-PD1 agents in patients with resectable stage IIIB-D melanoma. The main questions it aims to answer are:

* radiological and pathological response rate to three doses of antiPD1 agents;
* do radiological and pathological responses correlate with gut microbiota and melanoma molecular genetics features Participants will receive three doses of aPD1 monotherapy as per center routine practice and will undergo regional lymphadenectomy. Before treatment initiation patients will be asked to bring faeces probes and fill out dietary questionnaire as well as just before the surgery.

After sugery adjuvant therapy will be prescribed for 12 month and patients will be followed up according to institutional routine practice for 5 years.

The clinical efficacy of PD1 inhibitors on the 2-year recurrence-free survival of patients with resectable stage III B-D melanoma will be assessed. This indicator will be compared with a historical control group using adjuvant PD1 immunotherapy and targeted therapy. Various factors will be analyzed for their potential impact on immunotherapy effectiveness, including demographics, disease stage and sub-stage, molecular-genetic status of the tumor, composition of the tumor\&#39;s lymphoid infiltrate, LDH levels, gut microbiome composition, radiological and pathological response to treatment, and the development of immune-mediated adverse events. These findings may help optimize treatment by implementing neoadjuvant therapy for stage III B-D cutaneous melanoma.

formalin fixed paraffin embedded tissue tumor blocks faeces

MelPRO-0322 (CRISTINA Trial) [miCrobiome pRedIctS aPD1 effecTivnes In melaNoma pAtietns]

Neoadjuvant Monotherapy With Anti-PD1 Agents in Patients With Resectable Stage IIIB-D Melanoma: Analysis of Novel Biomarkers

IPD data could be aggregated later with another neoadjuvant study

Gut microbiota isolation and 16S-RNA clusterization

2-year disease-free survival: time from surgery to disease recurrence (either locoregional or distant) or death from any cause

Rate of pathological complete response, near-to-pCR, non-pCR/disease progression

Russian Academy of Medical Sciences

Senior researcher, MD, PhD

Melanoma, Cutaneous Malignant

Alfonso Medela, MsC

Jordi Barrachina, PhD

Jesús Gardeazabal, PhD

Rosa María Izu, PhD

Juan Antonio Ratón Nieto, PhD

Ana Sánchez Diez, PhD

Andy Aguilar, MsC

Taig Mac Carthy, MsC

Rosa María Ize, PhD

The goal of this Cross-sectional analytical observational study of clinical case series is to validate a Computer-aided diagnosis software developed by AI Labs Group for the identification of cutaneous melanoma in images of lesions taken with a dermatoscopic camera. This study will be carried out in patients with skin lesions with suspected malignancy seen at the Dermatology Department of the Cruces University Hospital and Basurto University Hospital. The main questions it aims to answer are:

* If the AI algorithm developed by AI Labs group is a valid tool to identify cutaneous melanoma in dermoscopic images with high reliability.
* Comparing the device\&#39;s performance with dermatologists, with primary care physicians\&#39; assessment to be considered in later phases.
* Assessing the utility and feasibility of the device in adverse environments with technical limitations.

In this way, patients with skin lesions with suspected malignancy seen at the Dermatology Department of the Cruces and Basurto University Hospitals will be recruited. Patients in this study will not receive any specific treatment as part of the research protocol. In addition, they will continue their regular prescribed medications and treatments as directed by their primary healthcare providers. This study does not require doing a follow-up of the subjects. Every patient only gets their skin lesions photographed at the time of visit.

Introduction Cutaneous melanoma (CM), a type of skin cancer, has seen a significant rise in incidence and mortality. It\&#39;s particularly aggressive and can metastasize rapidly, making it resistant to chemotherapy and radiotherapy. However, early detection through simple surgical excision is highly treatable. Differentiating between benign and malignant pigmented lesions, especially during visual examination, is challenging.

Due to low public awareness and limited access to dermatologists, melanoma often gets diagnosed at a later stage. To address this, there\&#39;s growing interest in computer-aided diagnostics (CAD) using Artificial intelligence (AI) for early melanoma detection. AI technologies have shown competence comparable to dermatologists in classifying lesions from photographs. Machine vision and AI present a significant opportunity for improving diagnosis.

Preventive activities and early diagnosis campaigns have improved patient survival, pointing at the fact that AI-based devices to assess skin lesion malignancy and distinguish between micro melanomas and other skin lesions like nevus and lentigines may further increase patient survival. This study aims to clinically validate the detection of cutaneous melanoma using computer vision and machine learning applications.

Objectives Hypothesis A CAD system powered by with machine vision allows early and non-invasive diagnosis of cutaneous melanoma in-vivo.

Primary objective

To validate that the artificial intelligence algorithm developed by AI Labs Group S.L. for the identification of cutaneous melanoma in images of lesions taken with a dermatoscopic camera achieves the following values:

* Area Under the Curve (AUC) greater than 0.8
* Sensitivity of 80% or higher
* Specificity of 70% or higher

Secondary objective

To compare the performance of the artificial intelligence algorithm developed by the manufacturer with the performance of healthcare professionals of different specializations:

Dermatologists Primary care physicians Validate the usefulness and feasibility of the artificial intelligence algorithm developed by the manufacturer in adverse environments with severe technical limitations, such as lack of instrumentation or lack of internet connection.

PRIMARY CARE PHYSICIANS The study does not compare the performance of the device against Primary care physicians; it only focuses on dermatologists. However, it is widely known that dermatologists have a significantly higher diagnostic success rate in the detection of melanoma.

Population Patients with skin lesions of suspected malignancy seen at the Dermatology Department of the Cruces and Basurto University Hospitals.

Design and Methods Design This is an analytical observational case series study for the performance of a diagnostic test study. Measurements are performed in a single case, so it is a cross-sectional study.

Number of Subjects The initial number of subjects for the study was 40. However, due to the need for a balanced dataset (i.e., same number of melanoma and non-melanoma images), we considered it necessary to collect cases of nevus and/or other types of skin lesions if necessary. For this reason, the proposed number of subjects was increased to approximately 200 people, of which at least 40 present cutaneous melanoma.

At the time of this report, a total of 96 subjects have been included in the study, 70 from Basurto University Hospital and 26 from Cruces University Hospital.

Initiation Date The date of inclusion of the first subject was September 17th, 2020.

Completion Date The last subject of the initial sample of 40 participants was included on March 24, 2021.

The readjusted target sample size (200 participants) has not been reached yet, with 96 subjects included at the time of the report.

Duration This study is estimated to have a recruitment period of 10 months for the inclusion of the first 40 patients. The recruitment period is extended by 12 months for the inclusion of patients up to a total of 200, with a minimum of 40 melanomas.

The total duration of the study is estimated at 36 months, including the time required after recruitment of the last subject for closing and editing the database, data analysis and preparation of the final study report.

Methods

All the skin lesions are photographed following these technical indications:

Uncompressed image format, such as PNG, HEIC or TIFF. Taken with the DermLite Foto X dermatoscope of the 3Gen Inc.

Taken from a Smartphone with the following characteristics:

With a camera with a minimum resolution of not less than 13 megapixels.

Taken with one of the following models:

* Google Pixel 3 and Google Pixel 3 XL.
* Samsung Galaxy Note 10, Samsung Galaxy S10, Samsung Galaxy S10E
* iPhone X and below
* Disabling all image post-processing, such as HDR, portrait mode, color filters or digital zoom.

On a monthly basis, the research team collects the images and verifies their correctness. If any image is not of sufficient quality, the investigator repeats the photograph. The research team also collects diagnostic data from the expert dermatologists.

Clinical Validation Study of an AI-based CAD System for Early Non-Invasive Detection of Cutaneous Melanoma

Clinical Validation Study of a CAD System With Artificial Intelligence Algorithms for Early Non-invasive Detection of in Vivo Cutaneous Melanoma

Number of images that every patient upload to the web app with tha AI algorithm

Quality of the uploaded image by patient. A bad quality will not be accepted for the study and the patient will be asked to upload an image with a better quality

Sensitivity of the algorithm to detect the presence of melanoma or not

Servicio Vasco de Salud Osakidetza, Spain

Osakidetza

Hospital de Basurto

Hospital de Cruces

AI Labs Group S.L

Respiratory Tract (Lung and Bronchial) Diseases

Symptoms and General Pathology

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Lung Neoplasms

Carcinoma, Non-Small-Cell Lung

Carcinoma

Recurrence

Carcinoma, Renal Cell

Kidney Neoplasms

Neoplasms, Glandular and Epithelial

Adenocarcinoma

Urologic Neoplasms

Urogenital Neoplasms

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Kidney Diseases

Urologic Diseases

Male Urogenital Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Renal Cell Carcinoma

Clear Cell Renal Cell Carcinoma

Antineoplastic Agents

All Drugs and Chemicals

Hematinics

Anti-Infective Agents

Pembrolizumab

Immunomodulating Agents

Nivolumab

Atezolizumab

Liver Extracts

Nelfinavir

Antibodies

Antibodies, Monoclonal

Immunoglobulins

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Immunologic Factors

HIV Protease Inhibitors

Protease Inhibitors

Enzyme Inhibitors

Anti-HIV Agents

Anti-Retroviral Agents

Antiviral Agents

Beginning 7-14 days prior to start of pembrolizumab, nivolumab, or atezolizumab, patients receive nelfinavir mesylate PO BID on days 1-7 or 1-14 (dependent upon when treatment is started) up to 11-12 weeks. Patients also receive pembrolizumab, nivolumab or atezolizumab IV over 30-60 minutes on day 1. Cycles repeat every 21-28 days in the absence of disease progression or unacceptable toxicity. Patients then undergo hypofractionated radiation therapy over 3-14 days starting after cycle 1 and before cycle 3 of pembrolizumab, nivolumab or atezolizumab. The study will exclude irradiation of liver metastases as an added precaution.

Undergo hypofractionated radiation therapy

Hypofractionated Radiation Therapy

Laboratory Biomarker Analysis

Nelfinavir Mesylate

Ramesh Rengan

This phase II trial studies how well image guided hypofractionated radiation therapy works with nelfinavir mesylate, pembrolizumab, nivolumab, and atezolizumab in treating patients with melanoma, lung cancer, or kidney cancer that has spread (advanced). Hypofractionated radiation therapy delivers higher doses of radiation therapy over a shorter period of time and may kill more tumor cells and have fewer side effects. Nelfinavir mesylate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Immunotherapy with monoclonal antibodies, such as pembrolizumab, nivolumab and atezolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving hypofractionated radiation therapy, nelfinavir mesylate, pembrolizumab, nivolumab and atezolizumab may work better in treating patients with melanoma, lung, or kidney cancer.

OUTLINE:

Beginning 7-14 days prior to start of pembrolizumab, nivolumab, or atezolizumab, patients receive nelfinavir mesylate orally (PO) twice daily (BID) on days 1-7 or 1-14 (dependent upon when treatment is started) up to 11-12 weeks. Patients also receive pembrolizumab, nivolumab or atezolizumab intravenously (IV) over 30-60 minutes on day 1. Cycles repeat every 21-28 days in the absence of disease progression or unacceptable toxicity. Patients then undergo hypofractionated radiation therapy over 3-14 days starting after cycle 1 and before cycle 3 of pembrolizumab, nivolumab or atezolizumab.

After completion of study treatment, patients are followed up at 30 days and then every 6 months for up to 2 years.

Image Guided Hypofractionated Radiation Therapy, Nelfinavir Mesylate, Pembrolizumab, Nivolumab and Atezolizumab in Treating Patients With Advanced Melanoma, Lung, or Kidney Cancer

ImmunoRad: Stratified Phase II Trial of Image Guided Hypofractionated Radiotherapy With Concurrent Nelfinavir and Immunotherapy in Advanced Melanoma, Lung Cancer, and Renal Cell Carcinoma

Will be determined by immune-related Response Evaluation Criteria in Solid Tumor 1.1. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by CT Scan: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.",

Any long term data in the medical record that showed survival was use to measure overall survival.

No RECIST measurable progression over the course of 2 years post-treatment. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions

Will be assessed by National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0. All adverse events that were attributable to study intervention in 20 participants, and counted the frequency of severity levels in the participants.

National Cancer Institute (NCI)

University of Washington

Professor

Beginning 7-14 days prior to start of pembrolizumab, nivolumab, or atezolizumab, patients receive nelfinavir mesylate PO BID on days 1-7 or 1-14 (dependent upon when treatment is started) up to 11-12 weeks. Patients also receive pembrolizumab, nivolumab or atezolizumab IV over 30-60 minutes on day 1. Cycles repeat every 21-28 days in the absence of disease progression or unacceptable toxicity. Patients then undergo hypofractionated radiation therapy over 3-14 days starting after cycle 1 and before cycle 3 of pembrolizumab, nivolumab or atezolizumab. The study will exclude irradiation of liver metastases as an added precaution.

Atezolizumab: Given IV

Hypofractionated Radiation Therapy: Undergo hypofractionated radiation therapy

Laboratory Biomarker Analysis: Correlative studies

Nelfinavir Mesylate: Given PO

Nivolumab: Given IV

Pembrolizumab: Given IV

Treatment (Nelfinavir, Immunotherapy, Radiation Therapy)

Age, Categorical

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Dr. Ramesh Rengan, Department Chair

Response Rate

2 Patients were lost to follow-up before 2 year mark, 1 patient passed away during treatment due to Myocardial infarction, so they were not considered in the OS data.

Overall Survival

2 participants were lost to follow-up before the 2-year mark.

1 Patient passed away during treatment due to a myocardial infraction.

Progression-free Survival

Percentage of mild adverse events

Percentage of Moderate Adverse Events

Percentage of Severe Adverse Events

Percentage of Life-Threatening Adverse Events

Number of Adverse Events

Bio-specimens have been collected and stored, and cannot be analyzed by a processing team due to COVID-19 staffing limitations.

Immune Correlative Studies: Changes in T-cell Repertoire

Overall Study

Anti-Arrhythmia Agents

Cardiotonic Agents

Digoxin

Trametinib

Dabrafenib

Protein Kinase Inhibitors

Protective Agents

Drugs: Dabrafenib 150mg PO 2x daily, Trametinib 2 mg PO daily, and Digoxin 0.25 mg PO daily for 8-week cycles.

Digoxin 0.25 mg PO daily will be given for 8-week cycles

Digoxin Combination

dabrafenib 150mg PO twice daily for 8-week cycles

trametinib 2 mg PO daily for 8-week cycles

Arthur Frankel, MD

This study is being done to find out if the combination of dabrafenib, trametinib and digoxin will lessen the side effects that you may experience and to measure your response and duration of response to the combination of drugs.

Melanoma is a cancer of melanocytes--melanin pigment producing cells, and the cancer originates in the skin, uvea, acral tissues and mucosal tissues. Melanoma incidence and mortality are increasing in the U.S. with over 80,000 cases/year and 9,000 deaths/year. Advanced melanoma occurs either after treatment for localized melanoma or de novo and is associated with chemo-resistance and a median survival of 9 months.

The study is a prospective, single-arm, one-site therapeutic trial of the combination of Dabrafenib + Trametinib + Digoxin for advanced V600 mutant melanoma.

A Clinical Trial of Patients With Melanoma

A Phase 1B Clinical Trial of Dabrafenib, Trametinib Plus Digoxin in Patients With Unresectable or Metastatic BRAF V600 Mutant Melanoma

DLTs will be defined based on the rate of drug-related grade 3-4 toxicities that do not resolve within 3 weeks or any toxicities requiring permanent discontinuation of any of the study drugs

University of Texas Southwestern Medical Center

Behaviors and Mental Disorders

Quality of Life

Bone Density Conservation Agents

Micronutrients

Vitamins

Vitamin D

Cholecalciferol

Ergocalciferols

Trace Elements

Hormones

Calcium

Calcium, Dietary

Vitamin D3

Calciferol

Ergocalciferol

Vitamin D2

placebo and vitamin D

Jean Y Tang, MD, PhD

The purpose of this study is to determine the signaling pathways and changes in gene expression in melanocytes of subjects with a history of non-melanoma skin cancer who are exposed to oral vitamin D. If vitamin D is found to inhibit a signaling pathway involved in the development of melanoma such as BRAF, a protein involved in cell proliferation, then oral vitamin D could be explored further as a chemoprevention for melanoma skin cancer.

Background:

Vitamin D is an important hormone that has multiple genetic effects in different tissue types that are mediated by signaling through the vitamin D receptor.

Recent studies have shown that vitamin D signaling results in decreased innate immunity and increased adaptive immunity.

Multiple epidemiologic studies have suggested that vitamin D may play a role in decreasing the risk of developing multiple types of cancer, including skin cancer.

In the context of the relative success of novel immune-related therapies including PD1 inhibitors, which improves immuno-surveillance, and ipilimumab, which suppresses T cell response, there is increased promise for treatment strategies that activate innate immunity. This led us to ask the question of whether vitamin D could increase immune surveillance for melanoma via increased activity of the adaptive immune system.

Prior studies performed by our group and others have suggested that vitamin D may play a role in decreasing melanoma risk. An epidemiologic study from the Women's Health Initiative showed that women with a prior history of NMSC who received calcium and vitamin D supplementation had a lower risk of subsequently developing melanoma. At the same time, women with a lower serum vitamin D level had a higher risk of developing melanoma. Furthermore, a recent clinical study showed that vitamin D supplementation increases serum vitamin D levels and ultimately results in increased vitamin D receptor signaling in benign nevi.

Taken together, this findings led us to ask whether oral vitamin D supplementation could impact immune signaling in benign nevi and potentially underpin a theoretical chemo-preventive role for vitamin D in melanoma.

Pilot Trial to Evaluate the Effect of Vitamin D on Melanocyte Biomarkers

Results will be submitted to scientific journal for publication.

Normal cells have a complex series of molecular signals that allow communication between cells and to the cell nucleus. These signals work together to control one or more cell functions, such as cell division or cell death. Abnormal signaling activity caused by changes in gene expression can lead to cancer. An understanding of abnormal signaling, both in the tumor and in normal tissues, may lead to new therapies in cancer patients. We wish to identify changes in molecular signaling that occur in the development of melanoma that might be suppressed in benign nevi (moles) in response to vitamin D supplementation.

We utilized a prior gene expression study that compared malignant melanoma cells to benign nevi (moles) and identified over 2300 genes that were differentially regulated in melanoma compared to benign nevi. There were approximately 270 genes in our data set that showed changes in expression after vitamin D treatment. We wish to identify overlap between these two groups.

National Institutes of Health (NIH)

National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

Stanford University

Associate Professor of Dermatology

4,000 IU oral vitamin D3

Vitamin D3: 4,000 IU oral vitamin D3

Arm A: Vitamin D

Arm B: Placebo

Placebo - subjects may cross over to vitamin D treatment after placebo treatment is complete

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
MelPRO-0322 (CRISTINA Trial) [miCrobiome pRedIctS aPD1 effecTivnes In melaNoma pAtietns]	NCT06299878	Melanoma, Skin Melanoma Stage ...	Gut microbiota ...	18 Years -	Russian Academy of Medical Sciences
Clinical Validation Study of an AI-based CAD System for Early Non-Invasive Detection of Cutaneous Melanoma	NCT06221397	Melanoma Melanoma, Skin		18 Years -	AI Labs Group S.L
Clinical Validation Study of an AI-based CAD System for Early Non-Invasive Detection of Cutaneous Melanoma	NCT06221397	Melanoma Melanoma, Skin		18 Years -	AI Labs Group S.L
Image Guided Hypofractionated Radiation Therapy, Nelfinavir Mesylate, Pembrolizumab, Nivolumab and Atezolizumab in Treating Patients With Advanced Melanoma, Lung, or Kidney Cancer	NCT03050060	Metastatic Kidn... Recurrent Lung ... Stage IV Cutane... Stage IV Renal ... Stage IV Lung N...	Atezolizumab Hypofractionate... Laboratory Biom... Nelfinavir Mesy... Nivolumab Pembrolizumab	18 Years -	University of Washington
A Clinical Trial of Patients With Melanoma	NCT02915666	Melanoma	Digoxin Combina... Dabrafenib Trametinib	18 Years -	University of Texas Southwestern Medical Center
Pilot Trial to Evaluate the Effect of Vitamin D on Melanocyte Biomarkers	NCT01477463	Melanoma, Skin	Vitamin D3 placebo and vit...	18 Years - 75 Years	Stanford University

Spots Global Cancer Trial Database for melanoma, skin