Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Symptoms and General Pathology

Rare Diseases

Melanoma

Neoplasm Metastasis

Pigmentation Disorders

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

Pharmaceutical Solutions

All Drugs and Chemicals

Anti-Infective Agents

Antineoplastic Agents

Analgesics

Aldesleukin

Immunomodulating Agents

Interleukin-2

Anti-HIV Agents

Anti-Retroviral Agents

Antiviral Agents

Two subcutaneous intralesional injections of Aldesleukin, prepared by the pharmacy such that the contents will be masked, will be administered by the care provider in a clinic seven days apart.

Two subcutaneous intralesional injections of Saline, prepared by the pharmacy such that the contents will be masked, will be administered by the care provider in a clinic seven days apart.

0.1 mL of sterile saline solution (0.9% m/v)

Saline

Carman A Giacomantonio, MD, FRCSC

This study is meant to assess the use of intralesional IL-2 to modulate the immunological response to suspected melanoma, or melanoma in situ, in an effort to increase lymphocyte infiltration and decrease disease metastasis.

Patients that are clinically diagnosed with suspected Melanoma or Melanoma in situ will be assigned to either a treatment or control arm. The treatment group will be subjected to two intralesional IL-2 injections, whereas the control group will be subjected to two intralesional injections of saline.

The proteomic and metabolomic profiles of both groups will be analyzed using urine and blood samples in an effort to assess the systemic immunological response, if any, to the treatment. Also, upon disease confirmation and staging by a qualified pathologist, lesions will be assessed for lymphocyte infiltration using immunohistochemical methods.

This study will determine whether pre-treatment of IL-2 on lesions (clinically diagnosed as melanoma or melanoma in situ) is effective in generating an adaptive immune response, and whether that immune response may play a role in preventing disease metastasis.

This study is primarily designed to determine if tumor specific immunity can be generated in patients with highly suspicious pigmented lesions in response to intralesional IL-2, and whether that immunity can confer resistance to melanoma metastasis. Patients will be identified by qualified dermatologists and interviews will be held at the surgery clinic (4th floor Dickson Center) QEII HSC, NSHA.

The standard wait time from consultation to surgical biopsy is up to 4 weeks. Investigators will ensure that patients are seen immediately upon notification from participating dermatologist and all research components of the study are completed within the normally anticipated wait time. Through utilization of this standard wait time, intralesional IL-2 can potentially affect an immune response, that otherwise could not be achieved after the biopsy is completed. Given that the study is conducted within the normal wait time, it doesn't deviate from the normal standard of care. Following the study protocol, patients will receive intralesional injections on Day 1(Week 1 Visit) and Day 8 (Week 2 Visit), and excisional biopsies will be performed on Day 15 (Week 3 Visit), well within the accepted wait time from consultation to biopsy. The intralesional injections and collection of biospecimens beyond the biopsy deviate from but does not delay the normal standard of care. Two additional visits are required in addition to the initial consultation.

This study is a randomized, controlled, double-blind study. Patients with highly suspicious pigmented lesions will be randomly assigned by an algorithm to one of two groups: 1) treatment group patients will be treated intralesionally with IL-2 (Proleukin (Aldesleukin), Novartis Pharmaceuticals Canada Inc.) at a dose of 500,000 International Units (IU) in 0.1ml of sterilized saline (0.9%, m/v) for 2 treatment cycles 1 week apart (Day 1 and Day 7); 2) control group patients will be treated intralesionally with sterilized saline (0.9%, m/v) of the same volume (0.1ml). Randomization will be generated by a Random Block algorithm for each patient, and instruction preparation for each patient will be sent to pharmacy. IL-2 (Proleukin) will be obtained from Novartis by the pharmacy, paid for by Dr. Carman Giacomantonio's research services account. The pharmacy will be given instruction to prepare either IL-2 treatment or injectable control (saline). The pharmacy will assign a codified ID which will be provided along with the syringe with the patient name labeled as "Interleukin-2/Placebo" (thus blinding study to clinician and patient). As a pilot study, the principle of the design is to test the feasibility of proceeding to a larger and more expensive trial following the methodology and protocol proposed. As such there will be a minimum of 20 (10 treatment, 10 placebo) participants (up to a maximum of 60). It is estimated that statistical significance will be reached with 20 patients, however if it is not reached after 20 patients, an additional 10 (5 treatment, 5 control) patients will be enrolled. If significance is still not reached after 30 patients, an additional 10 patients will be enrolled and so on up to a maximum of 60 patients. If after 60 patients, significance is not achieved then further recruitment under the current protocol would not be logical and therefore the methodology would need to be revised or study discontinued.

On Day 1 (first treatment) and 15 (excisional biopsy), all patients will have blood (4 vials) and urine (25-50 ml) samples taken. Local reactions to injections will be monitored for non- specific signs such as bleeding, arythema, infection, or irritation. Investigators do not anticipate specific changes in the pigmented lesion related to the injection in this short time period, however all changes will be noted.

On Day 15, following the second intralesional injection an excisional biopsy will be performed following standard surgical techniques, as follows: ellipse of skin encompassing the pigmented lesion extending into the subcutaneous fat will be performed to achieve a grossly clear but narrow margin of excision. This small defect will be closed primarily with interrupted sutures. The biopsied specimen will be subsequently evaluated using standard histological techniques to confirm diagnoses, assess margin status (clear or involved) and depth of lesion invasion. The depth of lesion invasion will dictate the extent of subsequent surgical excisions and margin selection according to standard National Comprehensive Cancer Network (NCCN) guidelines. Pre-biopsy intralesional injections of 0.1ml into the lesion will not alter dimensions or architecture of the lesion or impact the extent the subsequent biopsy required. Lesions that are felt to be too large for closure without tissue manipulation or creation of flaps, will be biopsied using a punch biopsy sampling technique whereby 4mm diameter discs of tissue from representative areas of the lesion will be taken to confirm the diagnosis and the depth of invasion. The depth of invasion will dictate the extent and complexity of subsequent surgery required to remove the lesion and achieve clear margins according to NCCN guidelines. The biopsied specimen will be processed as follows: using a 22G needle a fine needle aspiration biopsy will be performed (the needle will be passed through the center of the lesion two times) for RNA analysis. The remainder of the tissue will be sent to pathology for standard histological assessment. The pathologist will also report the extent of observed tumor infiltrating lymphocytes (TILs) associated with treatment compared to control injections. Blood and urine will be assessed using metabalomic and proteomic methods to assess systemic immune response to treatment.

All blood, urine, and lesion biopsy samples will be labeled with a codified number (will not contain any patient identifying information) and will be immediately transported to Dr. Carman Giacomantonio laboratory at Dalhousie University for storage. Fine needle aspiration of excised samples will be assessed for tumor genetic and epigeneitic profile. Blood and urine will be assessed for proteomic and metabolomic profiles, respectively.

All study participants will receive assessments every 4 months for 2 years and biannual assessments for years 3 to 5 after the initial intervention to assess disease progression, or the development of new melanoma, to compare between both treatment and control groups. There is no standardize test or measurable biomarker to assess established or lasting immunity. This aspect of the study is identical to the patient assessment conducted as per standard of care for melanoma patients. Again, any publications of study results will be completed devoid of any information that could be used to identify patients included in the study.

Patients will be given either intralesional IL-2 or intralesional saline as a control

Pre-Treatment of Highly Suspicious Pigmented Skin Lesions With Interleukin-2

Data will be analyzed in order to achieve a statistically significant differentiation between treatment and control outcomes in study measures including tumor infiltrating lymphocytes (TILs) and circulating immunomodulators.

All patients will receive assessments every 4 months for 2 years and then biannual assessments for years 3-5 after the initial intervention to assess disease metastasis in treatment and control groups. Both number of new metastases (integer value) and thickness (mm) will be measured as a part of this assessment.

RNA analysis of excised tissue will be compared to unaffected patient tissue obtained from the clear margins of the excisional biopsy to assess genetic changes resulting from the melanoma and treatment/placebo injections.

Proteomic analysis will be conducted on blood samples to assess systemic immune response to both treatment and control groups. Serum collected from patient blood samples will be used for proteomic analysis to assess protein expression, including circulating immunomodulators (cytokines and chemokines) before, and after, treatment. This study may serve to help develop diagnostic protocols and methods of assessing response to treatments.

Metabolomic analysis will be conducted on urine samples to assess systemic immune response to both treatment and control groups. All tumor and tissue produce by products in waste that are excreted by the kidneys. Urine samples can be evaluated using techniques, such as Mass Spectrometric, to determine if biological compounds can be identified in association with the presence of a malignant process that would not be produced by normal tissue.This study may serve to help develop diagnostic protocols and methods of assessing response to treatments.

Nova Scotia Health Authority

Carman Giacomantonio

Surgical Oncologist / General Surgeon / Professor

Carcinoma

Carcinoma, Squamous Cell

Carcinoma, Basal Cell

Exanthema

Bowen's Disease

Nevus, Epithelioid and Spindle Cell

Neoplasms, Glandular and Epithelial

Neoplasms, Squamous Cell

Neoplasms, Basal Cell

Nevus, Spindle Cell

Patients scheduled for excisional biopsy of skin lesion(s) will be invited to participate in this study. Photo-documentation of the skin neoplasm(s) in the ProRodinki application will be performed, and the generated report will be sent for evaluation by artificial intelligence. Following this procedure, an excisional biopsy of the lesion(s) will be scheduled. From the moment of inclusion in the study until the excisional biopsy, an interval of no more than 2-4 weeks is allowed. After excisional biopsy of the skin neoplasm(s), a routine intravital pathological examination with hematoxylin and eosin staining will be performed, if necessary, immunohistochemical and molecular genetic tests will be performed. The selected biosamples (paraffin blocks) will then be analyzed centrally by a morphologist.

Patient were underwent photography using mobile phone and tested application "ProRodinki"just before preplanned excisional or incisional biopsy.

Application AI result than will be compared with pathology report by independent investigator

Mobile phone application "ProRodinki"

Oxana E Garanina, MD, PhD

Irena Shlivko, Professor

Igor V Samoylenko, MD, PhD

Kirill A Baryshnikov

Lev V Demidov, Professor

Igor V Samoylenko

A Multicenter, Prospective, Low-interventional Clinical Study Evaluating on mobile application validation ("ProRodinki") in assessing the risk of skin malignant neoplasms

This is a multicentre, low-intervention, prospective study. In several centers, patients will be selected into 4 cohorts:

1. Patients with complaints of skin neoplasm(s) who have sought the help of a specialist to remove it(them), and patients with an established clinical diagnosis of suspicious/doubtful skin neoplasm(s) who are scheduled to undergo excisional biopsy to verify the diagnosis;
2. Patients who have complaints about a skin neoplasm(s) and consider it (them) suspicious without using the ProRodinki application and who have asked for help from a specialist in order to remove it(them);
3. patients who have complaints about skin neoplasm(s) and who, using the ProRodinki application, received a response that the neoplasm(s) is (are) suspicious / doubtful (s), and sought help from a specialist in order to remove it (their) to verify the diagnosis;
4. Cohort 4 (prospective): patients with suspicious/doubtful skin neoplasm(s) detected during an objective examination by a specialist without using the ProRodinki application, and who are scheduled for an excisional biopsy to verify the diagnosis .

Patients scheduled for excisional biopsy of skin lesion(s) will be invited to participate in this study. After signing the informed voluntary consent form in the ProRodinki application, an account will be created for the patient, in which a questionnaire will be filled out, photo-documentation of the skin neoplasm(s) will be performed, and the generated report will be sent for evaluation by artificial intelligence. The response received from the application for each clinical case will be recorded and all neoplasms will be grouped according to the classification of the application. Following this procedure, an excisional biopsy of the lesion(s) will be scheduled. From the moment of inclusion in the study until the excisional biopsy, an interval of no more than 2-4 weeks is allowed. Immediately before the excisional biopsy procedure, other non-invasive instrumental examinations (dermatoscopy, digital dermatoscopy) will be performed. After excisional biopsy of the skin neoplasm(s), a routine intravital pathological examination with hematoxylin and eosin staining will be performed, if necessary, immunohistochemical and molecular genetic tests will be performed. The selected biosamples (paraffin blocks) will then be analyzed centrally by a morphologist. All neoplasms will be classified according to the MPATH-Dx classification, the 2018 WHO classification of skin tumors, and will be assigned an ICD-O-3 code. For invasive melanomas, the characteristics necessary to establish the morphological stage of pT will also be collected (see also the Study Procedures section). The conclusion of the intravital pathoanatomical examination will be photo-documented through the ProRodinki application and attached to the patient's account in the tab where the photo of the removed neoplasm is stored.

This is a multicentre, low-intervention, prospective study. Patients scheduled for excisional biopsy of skin lesion(s) will be invited to participate in this study. Photo-documentation of the skin neoplasm(s) in the ProRodinki application will be performed, and the generated report will be sent for evaluation by artificial intelligence. Following this procedure, an excisional biopsy of the lesion(s) will be scheduled. From the moment of inclusion in the study until the excisional biopsy, an interval of no more than 2-4 weeks is allowed. After excisional biopsy of the skin neoplasm(s), a routine intravital pathological examination with hematoxylin and eosin staining will be performed, if necessary, immunohistochemical and molecular genetic tests will be performed. The selected biosamples (paraffin blocks) will then be analyzed centrally by a morphologist.

Clinical vAlidation of a MobilE appLication ("ProRodinki") in the Assessment of the maLignant skIn neoplAsms

A Multicentre, Prospective, Low-intervention Clinical Trial to Validate a Mobile Application ("ProRodinki") in Assessing the Risk of Skin Malignancies

Sensitivity will be calculated as the number of malignant neoplasms that are correctly classified, divided by all excised malignant neoplasms according to pathology report

Privolzhsky Research Medical University

MelanomaPRO, Russia

Eye Diseases

Carcinoma in Situ

Adenocarcinoma, Sebaceous

Eye Neoplasms

Adenocarcinoma

Neoplasms, Adnexal and Skin Appendage

Patients diagnosed with melanoma or/and nevus on the skin around the eye before surgery.

Patients diagnosed with basal cell carcinoma, squamous cell carcinoma, sebaceous gland carcinoma before surgery.

Chun Zhang, MD/PHD

Defu Wu, master

The purpose of this study is to establish a standardized process for obtaining digital pathological image information of ocular tumors; use modern pathological techniques to obtain the co-expression information of multiple biomarkers in the pathological tissues of ocular tumors, and finally construct standardized digital ocular tumors with biomarkers Pathology image database.

This study is a prospective study. Patients with common and representative ocular tumors in the Department of Ophthalmology, Peking University Third Hospital, will be selected and enrolled after informed consent to collect basic clinical information, preoperative blood samples, and ocular tumors Obtain pathological image annotation data and genomics-related data from ocular tumor tissue specimens, use blood samples for genomics information analysis, provide multi-dimensional data for the development of artificial intelligence algorithms, and establish artificial intelligence-assisted image data for eye tumors Standardize the process and establish a multi-modal ocular tumor standardized database of "clinical information-tissue samples-pathological images-genomics data". The database and the diagnosis system are correlated with each other to provide optimal image data for later machine learning and related algorithm establishment, and finally the investigators will be completed the design of a new artificial intelligence-assisted diagnosis system for eye tumors.

After the blood samples are treated with EDTA anti coagulation, the second-generation sequencing is performed from the DNA level and the RNA level to collect relevant genomics information, and establish an ocular tumor fusion genome database. Investigators will establish a complete sequencing data annotation database based on the existing tumor sequencing data annotation and analysis of soft nail sets and tumor sequencing data related public databases (such as the cosmic database).

Research of Pathological Imaging Diagnosis of Ocular Tumors Based on New Artificial Intelligence Algorithm

The result of OPAL automatic analysis will be compared with IHC manual counting analysis.The accuracy of the study will be declared "success" if OPAL automatic analysis meet more than 85% of the manual count for all antibody.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Pre-Treatment of Highly Suspicious Pigmented Skin Lesions With Interleukin-2	NCT03233828	Melanoma (Skin) Melanoma in Sit...	Aldesleukin Saline	18 Years - 80 Years	Nova Scotia Health Authority
Clinical vAlidation of a MobilE appLication ("ProRodinki") in the Assessment of the maLignant skIn neoplAsms	NCT05402046	Melanoma (Skin) Nevus Nevus, Spitz Nevus Halo Nevus, Pigmente... Basal Cell Carc... Squamous Cell C... Bowen's Disease Melanoma in Sit... Spot Pigmented	Mobile phone ap...	18 Years -	MelanomaPRO, Russia
Clinical vAlidation of a MobilE appLication ("ProRodinki") in the Assessment of the maLignant skIn neoplAsms	NCT05402046	Melanoma (Skin) Nevus Nevus, Spitz Nevus Halo Nevus, Pigmente... Basal Cell Carc... Squamous Cell C... Bowen's Disease Melanoma in Sit... Spot Pigmented	Mobile phone ap...	18 Years -	MelanomaPRO, Russia
Research of Pathological Imaging Diagnosis of Ocular Tumors Based on New Artificial Intelligence Algorithm	NCT04695015	Melanoma (Skin) Melanoma in Sit... Nevus Eye Sebaceous Gland... Basal Cell Carc... Squamous Cell C... Ocular Tumor		-	Peking University
Pre-Treatment of Highly Suspicious Pigmented Skin Lesions With Interleukin-2	NCT03233828	Melanoma (Skin) Melanoma in Sit...	Aldesleukin Saline	18 Years - 80 Years	Nova Scotia Health Authority

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