Neoplasms

All Conditions

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Rare Diseases

Carcinoma

Carcinoma, Merkel Cell

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Communicable Diseases

Polyomavirus Infections

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Carcinoma, Neuroendocrine

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Adenocarcinoma

Neoplasms, Nerve Tissue

Merkel Cell Carcinoma

Neuroendocrine Tumor

Neuroepithelioma

All Drugs and Chemicals

Antibodies

Immunoglobulins

Intervention only includes additional blood sampling at baseline and during follow up (5 samplings).

Samples

Mahtab SAMIMI, MD-PhD

Robert Loewe, MD

Robert Loewe

Helka Sahi, MD PhD

Helka Sahi

Jurgen Becker, MD PhD

Jurgen Becker

Paolo Ascierto, MD

Paolo Ascierto

Nicole KELLENERS-SMITH, MD PhD

Nicole KELLENERS-SMITH

Ana Maria Forsea, MD PhD

Ana Maria Forsea

John Paoli, MD PhD

John Paoli

Deniz SECKIN, MD

Deniz SECKIN

Agustin Martin-Clavijo, MD

Agustin Martin-Clavijo

Merkel cell carcinoma (MCC) is a rare aggressive skin carcinoma. Approximately 80% of MCC are related to the Merkel Cell Polyomavirus (MCPyV). Although rates of relapse are high, the follow-up strategy lacks consensus. Patients are usually assessed clinically every 3 to 6 months for the first 2-3 years, and every 6 to 12 months thereafter. In the European guidelines, patients with early stages are monitored with clinical examination and ultrasonography of lymph nodes, while whole-body imaging is optional in patients with stage III disease, on a yearly basis for 5 years. Such strategy may prevent the diagnosis of infra-clinical recurrences, whereas patients could still be treated with surgery or radiation therapy. Until 2017, patients with advanced disease were treated with chemotherapies, with no long-term benefit. Immunotherapies with PD-1/PD-L1 inhibitors currently allow durable responses in 50% of such patients. This major change in the management of MCC patients argues for a follow-up strategy that would allow early diagnosis of infra-clinical metastases, when tumoral burden is still low. Given that all patients cannot be monitored by systematic regular imaging, additional non-invasive tools are needed. Blood-based biomarkers as a surrogate of tumor burden are advantageous as they can be repeated over time, providing guidance on when imaging is necessary. The study aims to assess two blood biomarkers, MCPyV T-Ag antibodies and cell-free miR-375, in a prospective fashion from baseline diagnosis, in a cohort of 150 European MCC patients

SerUM Markers in MERkel Cell Carcinoma Patients: a Longitudinal moniTorIng Study for optiMization of European Guidelines

Diagnostic performances (specificity, sensitivity, predictive values) of each biomarker will be assessed at the end of follow up, in relation with patients' outcomes (remission and recurrence).

Cox regression analysis will be performed to evaluate the clinical and biological factors associated with recurrence, death of disease, response to treatments.

European Academy of Dermatology and Venerology

University Hospital, Tours

Skin and Connective Tissue Diseases

Skin Neoplasms

Antineoplastic Agents

Antibodies, Monoclonal

Immunomodulating Agents

Ipilimumab

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Ipilimumab is a recombinant, human monoclonal antibody that binds to CTLA-4. It is commercially available under the brand name Yervoy . The use of ipilimumab for MCC is investigational: a study-specific supply of medication will be provided by Bristol-Myers Squibb.

Isaac F Brownell, M.D.

Background:

- Ipilimumab is a drug used to treat melanoma that cannot be treated surgically. It targets a molecule found on T-cells in the human immune system. Blocking these molecules on the T-cells might allow the cells to help destroy melanoma cells more effectively. This drug has also been studied in other cancers such as prostate cancer and lung cancer, but not yet in Merkel cell carcinoma (MCC). Researchers think therapy like ipilimumab that enhances the immune system may be effective against MCC. They want to study how safe the drug is and its effect on the immune system and tumors.

Objectives:

- To determine the number of subjects with MCC who take the study drug that remain alive 12 months later.

Eligibility:

- Adults 18 years and older who have metastatic MCC.

Design:

* Participants will be screened with a medical history and physical exam.
* Participants will receive the study drug 4 times, one dose every 21 days. After the 4 visits, participants will receive a maintenance dose of the drug every 12 weeks until the drug is no longer beneficial.
* They will receive the drug through a plastic tube usually inserted in a vein on the arm.
* It will take 90 minutes to give each dose.
* At all visits, participants will be screened with a medical history, physical exam, and blood tests. Any tumors on their skin will be measured and photographed.
* Every 12 weeks during the study and maintenance period, participants will have a CT scan. Throughout the study and maintenance period, they will have blood and skin tests.

Background:

Merkel cell carcinoma (MCC) is a rare, aggressive neuroendocrine cancer of the skin with a mortality of approximately 33%. Approximately one-third of patients present with metastatic disease, for which there is no effective treatment. Merkel cell polyomavirus (MCV), a DNA virus that expresses T antigen oncoproteins, was found to be clonally integrated into the genome of the majority of MCC tumors. MCC tumor progression is believed to be associated with the development of immune evasion, and multiple lines of evidence (higher incidence in immunocompromised populations, reports of spontaneous regression, responses to immune modulators, and improved prognosis associated with CD8+ intratumoral lymphocytes) suggest that immunotherapy may improve outcomes in patients with advanced MCC. Ipilimumab is a recombinant, human monoclonal antibody that binds to cytotoxic Tlymphocyte- associated antigen 4 and has shown efficacy in metastatic melanoma.

Objectives:

Primary:

-Determine overall survival at 12 months.

Secondary:

* Determine the best overall response rate, as assessed by modified RECIST immunerelated response criteria, at week 12.
* Determine median survival.
* Determine disease-specific survival (DSS) and progression-free survival (PFS).
* Evaluate the safety and tolerability of ipilimumab in patients with metastatic MCC.
* Assess biomarkers of immune activation and MCV-specific immune response.

Eligibility:

* Patients (age greater than or equal to 18 years) with metastatic MCC (AJCC stage 3b or 4).
* Immunocompromised individuals and patients with autoimmune disease are excluded.

Design:

* Patients will enroll at the NIH Clinical Center, Bethesda, MD (primary site) or at a study sub-sites Memorial Sloan-Kettering Cancer Center, New York, NY; University of Michigan, Ann Arbor, MI; or University of Pennsylvania, Philadelphia, PA.
* Ipilimumab will be given at a dose of 10 mg/kg as a 90-minute intravenous infusion on day 1 of each 21-day cycle for 4 cycles. After 4 doses, patients may receive a maintenance dose every 12 weeks until disease progression or unacceptable toxicity, for up to an additional 4 doses.
* Imaging scans will be done at week 12, and every 12 weeks on study starting week 21.
* Patients will remain on-study for follow-up for 96 weeks after the last of the initial 4 doses.
* Response and progression will be evaluated using modified RECIST immune-related response criteria.

Study of the Drug Ipilimumab for Metastatic Merkel Cell Carcinoma

Phase II Open-Label Trial of Ipilimumab for Metastatic Merkel Cell Carcinoma

National Cancer Institute (NCI)

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
SerUM Markers in MERkel Cell Carcinoma Patients: a Longitudinal moniTorIng Study for optiMization of European Guidelines	NCT04705389	Merkel Cell Car...	Samples	-	University Hospital, Tours
Study of the Drug Ipilimumab for Metastatic Merkel Cell Carcinoma	NCT01913691	Merkel Cell Car...	Ipilimumab	18 Years - 100 Years	National Institutes of Health Clinical Center (CC)
SerUM Markers in MERkel Cell Carcinoma Patients: a Longitudinal moniTorIng Study for optiMization of European Guidelines	NCT04705389	Merkel Cell Car...	Samples	-	University Hospital, Tours

Spots Global Cancer Trial Database for merkel cell polyomavirus