Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Symptoms and General Pathology

Eye Diseases

Rare Diseases

Melanoma

Cicatrix

Uveal Neoplasms

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

Eye Neoplasms

Uveal Diseases

Intraocular Melanoma

Neuroendocrine Tumor

Neuroepithelioma

endoresection of the tumor scar or, when surgery is not possible, transpupillary thermotherapy on the tumor scar

Endoresection

Transpupillary thermotherapy by laser diode on the tumor scar

Laser diode

Nathalie CASSOUX, MD, PhD

Study the efficacy of endoresection of the tumor scar or, when surgery is not possible, transpupillary thermotherapy on the tumor scar to prevent neovascular glaucoma and secondary enucleation

Endoresection of the Tumor Scar or Transpupillary Thermotherapy for the Treatment of Large Uveal Melanomas (Endoresection-Laser)

Phase II Evaluating Endoresection of the Tumor Scar or Transpupillary Thermotherapy When Endoresection is Not Feasible After Proton Beam Therapy for the Treatment of Large Uveal Melanomas

observed complications are : Number of glaucomas, numbrer of retinal detachment and number of secondary enucleations.

Institut Curie

Antineoplastic Agents

All Drugs and Chemicals

Lenvatinib

Immune Checkpoint Inhibitors

Pembrolizumab

Antineoplastic Agents, Immunological

Protein Kinase Inhibitors

Enzyme Inhibitors

Lenvatinib 20 mg daily plus pembrolizumab 200 mg IV every 3 weeks.

200 mg IV every 3 weeks for a maximum of 2 years.

Chris Fountain, RN

Matthew Taylor, MD

The purpose of this study is to evaluate the efficacy of lenvatinib and pembrolizumab to treat metastatic uveal melanoma.

This is a phase II, single arm, single institution clinical trial. Adults (age≥18 years-old) with immune checkpoint inhibitor naïve metastatic uveal melanoma will be evaluated for eligibility. Eligible participants will be treated with the combination of Lenvatinib 20 mg daily + pembrolizumab 200 mg IV every 3 weeks for a maximum of 2 years.

Lenvatinib Plus Pembrolizumab In Patients With Immune Checkpoint Inhibitor Naïve Metastatic Uveal Melanoma

A Phase II Clinical Trial Evaluating The Combination Of Lenvatinib Plus Pembrolizumab In Patients With Treatment Naive Metastatic Uveal Melanoma

progression free survival, defined as the time from enrollment to the first documented evidence of disease progression or death.

Objective response rate (complete and partial responses assessed by iRECIST)

Overall survival, defined as the time from enrollment to death (resulting from any cause).

Adverse events (per CTCAE v5.0), frequency of treatment information, dose reduction, and treatment discontinuation due to treatment related adverse events (TRAE).

Merck Sharp & Dohme LLC

Eisai Inc.

Providence Health & Services

Head and Neck Neoplasms

Anticonvulsants

Central Nervous System Depressants

Psychotropic Drugs

Analgesics

Azacitidine

Valproic Acid

Interleukin-2

Antimetabolites

Analgesics, Non-Narcotic

Neurotransmitter Agents

* Accelerated titration phase I design and a subsequent single arm phase II study
* Prior to T cell transfer (day 0), patients will be treated with valproic acid (dose 50 mg/kg/d, 7d; days -9 to day -3) and 5' azacytidine (dose 75mg/m2/d, 7d; days -9 to day -3)
* Phase I: patients will be treated with one single intravenous administration of MC2 TCR T cells at 5 different escalated doses of 5x10E7, 5x10E8, 5x10E9,1.0x10E10, and the total number of cultured TCR T cells (i.e., usually 1.0-5.0 x10E10 TCR T cells). MC2 TCR T cell infusions will be supported by low dose of IL-2 administrations (s.c. 5x10E5 IU/m2 2qd for 5 days)
* T cells will be processed using IL-15 and IL-21 to generate young T cells

Adoptive therapy with autologous MC2 TCR T cells combined with AZA/VP

Adoptive therapy with autologous MC2 TCR T cells

A.A.M. van der Veldt, MD, PhD

R. Debets, PhD, Prof

R. Debets, PhD, Prof.

Karlijn de Joode, MD

Monique de Beijer, PhD

Cor Lamers, PhD

Single-centre, first-in-man phase I/II trial to demonstrate safety and efficacy of MAGE-C2/HLA-A2 TCR T cells (MC2 TCR T cells) in advanced melanoma (MEL) and head-and-neck carcinoma (HNSCC).

In this patient study, the investigators target the Cancer Germline Antigen (CGA) MAGE-C2 (MC2), and use T cells with a young phenotype. MC2 is highly expressed in melanoma (MEL) and head-and-neck squamous cell carcinoma (HNSSC), but not in healthy adult tissues. The investigators isolated MC2-specific TCRs from MEL patients who showed clinical responses following vaccination that were accompanied by significant frequencies of anti-MC2 CD8 T cells in blood and tumor without apparent side effects. Following extensive evaluation of in vitro anti-tumor and self-reactivities, the investigators have selected a TCR that recognizes the ALK epitope in the context of HLA-A2 for clinical development. Furthermore, preclinical studies showed that epigenetic pretreatment of tumor cells, but not normal cells, up-regulated MC2 gene expression and resulted in enhanced recognition of MC2 by the selected TCR. In parallel to the above studies, the investigators renewed their GMP protocol to process T cells, using stimulating antibodies and cytokines, to generate T cells with a young phenotype.

In the current phase I/II study, the investigators explore the safety and anti-tumor efficacy of T cells engineered with the selected TCR in patients with MC2-positive MEL and HNSSC. The study contains the following unique elements:

* CGA not targeted before by T cell therapy
* New T cell processing method to generate young T cells
* Pretreatment of patients with epigenetic drugs
* No chemotherapy prior to T cell infusion

Leads:

* Clinical PI: Astrid van der Veldt, MD, PhD
* Clinical logistics: Karlijn de Joode, MD
* T cell production: Monique de Beijer, PhD; and Cor Lamers, PhD
* Coordinator/Preclinical PI: prof. Reno Debets, PhD

MAGE-C2 TCR T Cell Trial to Treat Melanoma and Head and Neck Cancer

Adoptive Therapy With TCR Gene-engineered T Cells to Treat Patients With MAGE-C2-positive Melanoma and Head and Neck Cancer

MTD is determined using an accelerated titration phase with T cell doses as described in treatment arm; AEs are recorded according to CTCAE 5.0

Anti-tumor responses are recorded according to RECIST v1.1 using the MTD from outcome 1

Ludwig Institute for Cancer Research

Dutch Cancer Society

Stichting Coolsingel Rotterdam grant

Jan Ivo Stichting grant

Erasmus Medical Center

Principal Investigator

Oculocerebral Syndrome With Hypopigmentation

Radiopharmaceuticals

Participants randomized to this arm will receive imaging agent \[203Pb\]VMT01 and undergo SPECT/CT imaging first. Later, participants in this arm will receive \[68Ga\]VMT02 and undergo PET/CT imaging.

Participants randomized to this arm will receive imaging agent \[68Ga\]VMT02 and undergo PET/CT imaging first. Later, participants in this arm will receive \[203Pb\]VMT01 and undergo SPECT/CT imaging.

Diagnostic imaging radiopharmaceutical; by intravenous infusion

[203Pb]VMT01

[68Ga]VMT02

Frances L Johnson, MD

Geoffrey B Johnson, MD, PhD

The study hypothesis is that new imaging agents \[203Pb\]VMT01 and \[68Ga\]VMT02 can be safely used in humans without independent biological effect and can be used to image melanoma tumors expressing the melanocortin sub-type 1 receptor (MC1R) by SPECT/CT and PET/CT imaging modalities respectively.

This is a first-in-human study evaluating the suitability of \[203Pb\]VMT01 for SPECT/CT imaging and \[68Ga\]VMT02 for PET/CT imaging of MC1R-expressing metastatic melanoma. Study results will provide foundational data to develop imaging and dosing for future therapeutic trials of \[212Pb\]VMT01 for the treatment of metastatic melanoma.

The study will be a cross-over study with the participants serving as their own comparator. Participants with positive FDG-PET scans for stage IV (or inoperable stage III) metastatic melanoma will undergo SPECT/CT scans utilizing \[203Pb\]VMT01 followed a few weeks later by PET/CT scans utilizing \[68Ga\]VMT02, or vice versa. The order of the imaging agents will be randomly assigned.

Archived tumor tissue will be tested for expression of the imaging target, melanocortin receptor sub-type 1 (MC1R). The qualified researcher who tests the sample, and the independent pathologist who reviews the results, will be blinded to a participant's identifying information and imaging results. Evaluators will not have access to the medical record.

A pool of three qualified readers will evaluate study images (PET/CT and SPECT/CT). Images and medical information given to the readers will not include a participant's identifying information. The reader pool will not know the sequence of imaging for a participant or have access to the medical record.

An independent medical physicist will validate imaging results and measurements of radiation absorbed and excreted by the participant's body. The physicist will be blinded to participant identifiers and demographics, as well as the sequence of imaging for a participant. The physicist will not have access to the medical record.

Targeted Imaging of Melanoma for Alpha-Particle Radiotherapy

A Phase 1 Cross-over Biodistribution Study of [203Pb]VMT01 for Single Photon Emission Computed Tomography (SPECT) Imaging and [68Ga]VMT02 for Positron Emission Tomography (PET) Imaging of Stage IV Metastatic Melanoma

All de-identified individual participant data (IPD) that underlies results in a peer-reviewed scientific publication will be shared.

Adverse Events (AEs) will be assessed for severity according to CTCAE v5.0 and for relatedness to each of the investigative imaging agents (\[203Pb\]VMT01 and \[68Ga\]VMT02). Assessments attributed as possibly, probably, or definitely related to the imaging agent will be considered related.

Biodistribution will be calculated by utilizing PET/CT scans.

Biodistribution will be calculated by utilizing SPECT/CT scans.

Cmax will be determined by blood sampling and direct radioactivity measurements.

AUC will be determined by blood sampling and direct radioactivity measurements.

Renal excretion will be determined by urine sampling and direct radioactivity measurements.

Dosimetry will be modeled by utilizing the SPECT/CT scans.

Archived (previously collected) tumor tissue will be tested for MC1R expression and compared to study images obtained using MC1R targeted imaging agents, \[203Pb\]VMT01 and \[68Ga\]VMT02. The data will be assessed for an association between positive tissue and positive images.

Sites of cancer detected previously by imaging will be compared to the presence or absence of positive imaging scans with the study agents, \[203Pb\]VMT01 and \[68Ga\]VMT02.

For a given participant, dosimetry calculations will be compared between the two imaging agents with respect to cumulative absorbed dose of radiation.

Mayo Clinic

Perspective Therapeutics

Pharmaceutical Solutions

tebentafusp weekly IV escalating in the first treatment cycle with dose 20 mcg on day 1, 30 mcg on day 8, 68 mcg on days 15 and 22. Thereafter weekly doses will be 68 mcg IV for 6 months.

Tebentafusp supplied as concentrate for solution for infusion and diluted prior to administration. 0.2 mg/mL drug product will be provided as a sterile, refrigerated solution in glass vials.

Tebentafusp

Lisa Poulton

Elizabeth Reilly

Pippa Corrie

Pavlina Spiliopoulou

Joesph Sacco

Heather Shaw

Rebecca Lee

Paul Nathan

Mark Middleton

Sarah Danson

Researchers are trying to find ways to improve the management of people with intermediate or high risk resected cutaneous melanoma or with primary uveal melanoma.

This research study is investigating using a new blood test to decide when to give a drug called tebentafusp. Tebentafusp has been used in clinical trials in patients with advanced cutaneous and uveal melanoma. This study is designed to determine if tebentafusp can help patients with cutaneous or uveal melanoma live longer.

TebeMRD is an unblinded non-randomised, open labelled, safety and efficacy study involving 2 patient cohorts:

* A: Cutaneous melanoma with molecular relapsed disease (MRD)
* B: Uveal melanoma with MRD

Approximately 850 patients (600 cutaneous melanoma, 250 uveal melanoma) will be enrolled from 50 centres to screen for HLA-A\*0201 status and then followed for up to 24 months for MRD at those same centres. Patients identified with MRD will be invited to be treated with tebentafusp at up to 10 treating centres in the UK. Patients in cohorts A and B will receive up to six months of tebentafusp, administered weekly IV, and then will be followed-up for 12 months for molecular and clinical relapse.

Patients will be in the pre-screening phase for determination of HLA-A\*0201 status for up to 2 weeks. Those patients who are positive for HLA-A\*0201 will be followed for MRD and will attend the clinical sites for 3 monthly testing for up to 24 months. Patients will leave the study if no molecular relapse is detected during the molecular screening period. When MRD is identified, patients will be evaluated for eligibility to enter the main study at one of up to 10 specialist treatment centres, where patients will enter the screening period for determination of eligibility to start tebentafusp administration within 6 weeks. After a maximum 6 months treatment patients will be followed up for 12 months, or until the study is completed, if this is longer.

Tebentafusp in Molecular Relapsed Disease (MRD) Melanoma

A Phase II Non-Randomized, Open-label, Multi-centre Study of the Safety and Efficacy of Tebentafusp in Melanoma With Molecular Relapsed Disease

Best molecular response in cohorts A and B

Best response to treatment, with partial molecular response (pMR) defined as a decrease in the allele frequency of the index mutation(s), and complete molecular response (cMR) as no detectable mutation(s)

Evaluate the efficacy of tebentafusp in each cohort - Relapse free survival at 12 months; duration of MR; overall survival

Assess the safety and tolerability of tebentafusp in MRD. Incidence and severity of adverse events according to NCIC CTCAE v5.0/2019 Lee et all criteria; dose reductions, interruptions and cessations in the course of treatment

Percentage of patients with molecular relapse at baseline, within 6 months and over 12 months of monitoring

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Endoresection of the Tumor Scar or Transpupillary Thermotherapy for the Treatment of Large Uveal Melanomas (Endoresection-Laser)	NCT02874040	Uveal Melanoma Melanoma, Uveal	Endoresection Laser diode	18 Years -	Institut Curie
Lenvatinib Plus Pembrolizumab In Patients With Immune Checkpoint Inhibitor Naïve Metastatic Uveal Melanoma	NCT05308901	Melanoma, Uveal	Pembrolizumab Lenvatinib	18 Years -	Providence Health & Services
MAGE-C2 TCR T Cell Trial to Treat Melanoma and Head and Neck Cancer	NCT04729543	Melanoma Melanoma, Uveal Head and Neck C...	Adoptive therap...	18 Years -	Erasmus Medical Center
Lenvatinib Plus Pembrolizumab In Patients With Immune Checkpoint Inhibitor Naïve Metastatic Uveal Melanoma	NCT05308901	Melanoma, Uveal	Pembrolizumab Lenvatinib	18 Years -	Providence Health & Services
Lenvatinib Plus Pembrolizumab In Patients With Immune Checkpoint Inhibitor Naïve Metastatic Uveal Melanoma	NCT05308901	Melanoma, Uveal	Pembrolizumab Lenvatinib	18 Years -	Providence Health & Services
Endoresection of the Tumor Scar or Transpupillary Thermotherapy for the Treatment of Large Uveal Melanomas (Endoresection-Laser)	NCT02874040	Uveal Melanoma Melanoma, Uveal	Endoresection Laser diode	18 Years -	Institut Curie
Endoresection of the Tumor Scar or Transpupillary Thermotherapy for the Treatment of Large Uveal Melanomas (Endoresection-Laser)	NCT02874040	Uveal Melanoma Melanoma, Uveal	Endoresection Laser diode	18 Years -	Institut Curie
Targeted Imaging of Melanoma for Alpha-Particle Radiotherapy	NCT04904120	Melanoma (Skin) Melanoma Stage ... Melanoma, Uveal Melanoma, Mucos...	[203Pb]VMT01 [68Ga]VMT02	18 Years - 89 Years	Perspective Therapeutics
MAGE-C2 TCR T Cell Trial to Treat Melanoma and Head and Neck Cancer	NCT04729543	Melanoma Melanoma, Uveal Head and Neck C...	Adoptive therap...	18 Years -	Erasmus Medical Center
Tebentafusp in Molecular Relapsed Disease (MRD) Melanoma	NCT05315258	Melanoma (Skin) Melanoma, Uveal	Tebentafusp	18 Years -	University of Oxford

Spots Global Cancer Trial Database for melanoma, uveal