Melanoma
Conditions
Keywords
anti-PD1 therapy, immune checkpoint blockade, dysplastic nevi, BRAF and NRAS mutations
Brief summary
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.
Detailed description
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.
Interventions
DRUGSingle agent, adjuvant anti-PD1 therapy
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
Sponsors
John Kirkwood
Melanoma Research Foundation
VeyTel Inc.
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Subjects must have at least two atypical nevi of ≥ 4 mm diameter. 2. Subjects must have a current documented history of melanoma. 3. Subject must be ≥ 18 years and if female of childbearing potential, must agree to practice effective contraception per institutional SOC if sexually active. 4. Subjects will have been deemed candidates for adjuvant therapy with single agent anti-PD1 therapy. 5. Subjects must give written informed consent to participate in this study with consent signed and dated prior to entry into trial.
Exclusion criteria
1. Patients with non-malignant diseases or indications that would preclude the administration of anti-PD1 therapy such as significant immune suppression or active autoimmune disease requiring disease modifying, immunosuppressive therapy, will be ineligible. 2. Patients who have previously received anti-PD1 therapy 3. Patients with history of other active, non-melanoma cancers 4. Patients who are receiving other anti-neoplastic therapy.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in the aggregate pigmentation | Pre-treatment, up to 12 months | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in predefined atypical nevi - size | Pre-treatment, up to 12 months | 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. |
| Change in predefined atypical nevi - margin | Pre-treatment, up to 12 months | 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. |
| Change in predefined atypical nevi - pigmentation | Pre-treatment, up to 12 months | 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. |
| Change in histopathologic features of A/DN - cellular infiltrate | Pre-treatment, up to 12 months | Histopathologic changes within atypical nevi that are biopsied will be assessed by an expert dermatopathologist for the dendritic cell and lymphocytic cell immune infiltrate. |
| Change in histopathologic features of A/DN - regression features | Pre-treatment, up to 12 months | Histopathologic changes within atypical nevi that are biopsied will be assessed by an expert dermatopathologist for regression features including fibrosis and vascularization. |
| Change in histopathologic features of A/DN - cytologic features | Pre-treatment, up to 12 months | Histopathologic changes within atypical nevi that are biopsied will be assessed by an expert dermatopathologist for cytologic features including nuclear size and atypia. |
| Change in histopathologic features of A/DN - dysplastic features | Pre-treatment, up to 12 months | Histopathologic changes within atypical nevi that are biopsied will be assessed by an expert dermatopathologist for dysplastic features of nevi including cell architecture. |
Countries
United States
Contacts
CONTACTDanielle L Bednarz, RN
CONTACTAmy Rose, RN
PRINCIPAL_INVESTIGATORJohn M Kirkwood, MD
UPMC Hillman Cancer Center
Outcome results
None listed