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| Name | Class |
|---|---|
| Melanoma Research Foundation | OTHER |
| VeyTel Inc. | UNKNOWN |
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This study will examine the impact of anti-programmed cell death 1 (PD1) therapy given in the approved adjuvant therapeutic regimens upon the morphologic, histopathologic, molecular and immunologic as well as genomic features of atypical/dysplastic nevi (A/DN) in patients with a prior documented melanoma of Stages IIB, IIC, IIIA, IIIB, or IIIC and concurrent presence of two or more atypical nevi.
Given the established efficacy of anti-PD1 therapy as an adjuvant treatment in both advanced nodal and earlier stage deep primary node negative melanoma, this study hypothesizes that anti-PD1 therapy may provide a basis for effective therapeutic prevention. To study if anti-PD1 therapy can help prevent the development of melanoma, this study will examine its effects upon atypical/dysplastic nevi, which are well established as non-obligate pre-cursor lesions that are markers of increased risk of melanoma. This single agent, adjuvant study will evaluate the impact of adjuvant anti-PD1 therapy on morphology, histopathology, immunologic/molecular features, and gene expression of atypical/dysplastic nevi present in patients with stage IIB-III melanoma. This study aims to determine if anti-PD1 therapy will increase CD8 T cell responses to melanoma antigens, resulting in immune surveillance and anti-tumor immune responses within A/DN. It postulates that in response to anti-PD1 therapy, the aggregate pigmentation of total nevi including atypical/dysplastic nevi and benign melanocytic nevi will decrease with a measurable morphologic response. This study also asserts that there will be histopathologic changes within A/DN including increased density of immune infiltrate and increased presence of regression features. Increased anti-tumor immune response measured by increased CD8, IFN-y, and PD-1 expression within nevi is anticipated, along with a decrease in genes involved in pathways of melanomagenesis, pigmentation, and inflammation.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Patients Treated with single agent, adjuvant anti-PD1 therapy | Patients receiving single agent, adjuvant anti-PD1 therapy (given either as standard of care or as part of a separate investigational study) |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Single agent, adjuvant anti-PD1 therapy | Drug | One of the following Single-agent, adjuvant anti-PD1 therapies: Nivolumab is a type of targeted therapy drug called an immune checkpoint inhibitor (a type of immunotherapy). It is a monoclonal antibody that binds to the protein PD-1 on the surface of immune cells called T cells. It works by keeping cancer cells from suppressing the immune system. Dose = 240 mg IV every 2 weeks/480 mg every 4 weeks or, Pembrolizumab is a monoclonal antibody and a type of immune checkpoint inhibitor that's used in cancer immunotherapy. It works by attaching to the PD-1 protein on the surface of T cells, which are immune cells. This prevents cancer cells from suppressing the immune system, allowing the immune system to attack and kill the cancer cells. Dose = 200 mg IV every 3 weeks/ 400 mg every 6 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Change in the aggregate pigmentation | Percentage change in the total aggregate pigmentation including A/DN and benign melanocytic nevi. Percent change will be quantified from posterior trunk digital photographic images utilizing DermViz automated image comparison software. | Pre-treatment, up to 12 months |
| Measure | Description | Time Frame |
|---|---|---|
| Change in predefined atypical nevi - size | Change in size of predefined atypical nevi at the level of the individual nevus, as documented by dermoscopy. An expert clinician panel will evaluate pre- and post-treatment dermoscopic images in a blinded manner to score the visual features of nevus atypia. | Pre-treatment, up to 12 months |
| Measure | Description | Time Frame |
|---|---|---|
| Change in Expression of SOX-10 and BRAF | Quantify change in expression of key genes of melanomagenesis in A/DN in response to anti-PD1 therapy, measured via bulk RNA-sequencing performed on biopsied nevus specimens. | Pre-treatment, up to 12 months |
| Change in CD-8 T lymphocytes |
Inclusion Criteria:
Exclusion Criteria:
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Patients with a prior documented melanoma of Stages IIB, IIC, IIIA, IIIB, or IIIC and concurrent presence of two or more atypical nevi who have received anti-programmed cell death 1 (PD1) therapy given in the approved adjuvant therapeutic regimens.
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Danielle L Bednarz, RN | Contact | (412) 623-1191 | bednarzdl@upmc.edu | |
| Amy Rose, RN | Contact | 4126478587 | kennaj@upmc.edu |
| Name | Affiliation | Role |
|---|---|---|
| John M Kirkwood, MD | UPMC Hillman Cancer Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| UPMC Hillman Cancer Center | Recruiting | Pittsburgh | Pennsylvania | 15232 | United States |
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| ID | Term |
|---|---|
| D008545 | Melanoma |
| D004416 | Dysplastic Nevus Syndrome |
| D009477 | Hereditary Sensory and Autonomic Neuropathies |
| ID | Term |
|---|---|
| D018358 | Neuroendocrine Tumors |
| D017599 | Neuroectodermal Tumors |
| D009373 | Neoplasms, Germ Cell and Embryonal |
| D009370 | Neoplasms by Histologic Type |
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| ID | Term |
|---|---|
| D004364 | Pharmaceutical Preparations |
| D000077594 | Nivolumab |
| C582435 | pembrolizumab |
| ID | Term |
|---|---|
| D061067 | Antibodies, Monoclonal, Humanized |
| D000911 | Antibodies, Monoclonal |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
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Biopsy of one nevus will be performed at baseline (A) and at 3 month follow up (B). Tissue biopsies will be obtained after photographs and dermoscopic imaging has been performed at each time point.
|
|
| Change in predefined atypical nevi - margin |
Change in margin of predefined atypical nevi at the level of the individual nevus, as documented by dermoscopy. An expert clinician panel will evaluate pre- and post-treatment dermoscopic images in a blinded manner to score the visual features of nevus atypia. |
| Pre-treatment, up to 12 months |
| Change in predefined atypical nevi - pigmentation | Change in pigmentation of predefined atypical nevi at the level of the individual nevus, as documented by dermoscopy. An expert clinician panel will evaluate pre- and post-treatment dermoscopic images in a blinded manner to score the visual features of nevus atypia. | Pre-treatment, up to 12 months |
| Change in histopathologic features of A/DN - cellular infiltrate | Histopathologic changes within atypical nevi that are biopsied will be assessed by an expert dermatopathologist for the dendritic cell and lymphocytic cell immune infiltrate. | Pre-treatment, up to 12 months |
| Change in histopathologic features of A/DN - regression features | Histopathologic changes within atypical nevi that are biopsied will be assessed by an expert dermatopathologist for regression features including fibrosis and vascularization. | Pre-treatment, up to 12 months |
| Change in histopathologic features of A/DN - cytologic features | Histopathologic changes within atypical nevi that are biopsied will be assessed by an expert dermatopathologist for cytologic features including nuclear size and atypia. | Pre-treatment, up to 12 months |
| Change in histopathologic features of A/DN - dysplastic features | Histopathologic changes within atypical nevi that are biopsied will be assessed by an expert dermatopathologist for dysplastic features of nevi including cell architecture. | Pre-treatment, up to 12 months |
Changes in the immune microenvironment of A/DN in response to anti-PD1 therapy. Changes in T cell subsets will be quantified and compared pre- and post-treatment via multiplex IHC and multiplex IF performed on biopsied specimens. |
| Pre-treatment, up to 12 months |
| Change in T-regs | Changes in the immune microenvironment of A/DN in response to anti-PD1 therapy. Changes in regulatory T cells will be quantified and compared pre- and post-treatment via multiplex IHC and multiplex IF performed on biopsied specimens. | Pre-treatment, up to 12 months |
| Change in IFN-y immune transcriptional signature | Changes in the immune microenvironment of A/DN in response to anti-PD1 therapy. Changes in IFN-y immune transcriptional signature will be quantified and compared pre- and post-treatment via multiplex IHC and multiplex IF performed on biopsied specimens. | Pre-treatment, up to 12 months |
| Change in IL-6 immune transcriptional signature | Changes in the immune microenvironment of A/DN in response to anti-PD1 therapy. Changes in Immune transcriptional signature will be quantified and compared pre- and post-treatment via multiplex IHC and multiplex IF performed on biopsied specimens. | Pre-treatment, up to 12 months |
| Change in IL-10 immune transcriptional signature | Changes in the immune microenvironment of A/DN in response to anti-PD1 therapy. IL-10 immune transcriptional signature will be quantified and compared pre- and post-treatment via multiplex IHC and multiplex IF performed on biopsied specimens. | Pre-treatment, up to 12 months |
| Change in PD1 expression | Changes in the immune microenvironment of A/DN in response to anti-PD1 therapy. Changes in PD1 expression will be quantified and compared pre- and post-treatment via multiplex IHC and multiplex IF performed on biopsied specimens. | Pre-treatment, up to 12 months |
| D009369 | Neoplasms |
| D009380 | Neoplasms, Nerve Tissue |
| D018326 | Nevi and Melanomas |
| D012878 | Skin Neoplasms |
| D009371 | Neoplasms by Site |
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
| D009506 | Nevus |
| D009386 | Neoplastic Syndromes, Hereditary |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D009421 | Nervous System Malformations |
| D009422 | Nervous System Diseases |
| D020271 | Heredodegenerative Disorders, Nervous System |
| D019636 | Neurodegenerative Diseases |
| D011115 | Polyneuropathies |
| D010523 | Peripheral Nervous System Diseases |
| D009468 | Neuromuscular Diseases |
| D000013 | Congenital Abnormalities |
| D007162 |
| Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |