Evolution of Metabolic and Immune Dysfunction in In-transit Melanoma

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Evolution of Metabolic and Immune Dysfunction in In-transit Melanoma

Study Purpose

Melanoma in-transit metastases (ITMs) continue to represent a therapeutic dilemma, in that no standard method of treatment has been uniformly adopted. The complexity and heterogeneity of patient and disease characteristics, including the location and number of ITMs presents a barrier to a one size fits all treatment approach. Treatment of patients with limited regional disease remains challenging. Patients are typically treated with a combination of surgery, regional therapy, systemic therapy. Data on the management of ITMs is limited, even with the availability of immunotherapy (IMT). This study will use the unique etiology of ITMs to facilitate the understanding of how individual lesions metabolically and immunologically evolve as they move away from the primary tumor site. It is hypothesize that as ITMs move away from the primary melanoma site each will harbor progressively hypermetabolic tumor cells and a harsher microenvironment.

Recruitment Criteria

Accepts Healthy Volunteers Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms	No
Study Type An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes. An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes. Searching Both is inclusive of interventional and observational studies.	Observational
Eligible Ages	18 Years and Over
Gender	All

More Inclusion & Exclusion Criteria

Inclusion Criteria:

1. Be willing and able to provide written informed consent for the trial. 2. Be ≥ 18 years of age on day of signing informed consent. 3. A histological diagnosis of melanoma and at least two in-transit lesions at distinct distances from the primary site. Patients may be enrolled on the basis of a diagnosis of in-transit disease by a treating melanoma oncologist. 4. Cutaneous, mucosal or uveal melanoma are permitted. 5. Patients may be on treatment or treatment naïve. 6. Female patients of childbearing potential must have a negative urine or serum pregnancy test within 7 days from the time of pimonidazole administration.

Exclusion Criteria:

1. Subjects with in-transit disease that is not amenable to biopsy per the treating physician are excluded. 2. Subjects with known chronic immunosuppression (such as biologic agents like remicade, mycophenolate, methotrexate, prednisone >20 mg daily). 3. Subjects who are known to be HIV+, Hep B or Hep C positive.

Trial Details

Trial ID: This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.	NCT04658303
Phase Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans. Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data. Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs. Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.
Lead Sponsor The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.	Yana Najjar
Principal Investigator The person who is responsible for the scientific and technical direction of the entire clinical study.	Yana Najjar, MD
Principal Investigator Affiliation	UPMC Hillman Cancer Center
Agency Class Category of organization(s) involved as sponsor (and collaborator) supporting the trial.	Other
Overall Status	Recruiting
Countries	United States
Conditions The disease, disorder, syndrome, illness, or injury that is being studied.	Melanoma

Additional Details

This study will use a novel platform to profile patient biopsies, including microscopic analysis, flow cytometry for phenotyping, metabolic, and functional analyses, and metabolic profiling by Seahorse analysis to understand the unique etiology of ITMs to understand how individual melanoma lesions metabolically and immunologically evolve as they move away from the primary tumor site. A large amount of translational data is able to be derived from from an individual tissue biopsies. This study will utilize this platform to extensively evaluate 2-5 (melanoma) in-transit metastases (ITMs) per patient. It is hypothesized that as ITMs move away from the primary melanoma site each will harbor progressively hypermetabolic tumor cells and a harsher microenvironment. Each ITM station will be deeply profiled using metabolic assays, flow cytometry, and highly multiplexed immunofluorescent microscopy including, to interrogate the metabolic profiles of tumor and immune system in individual melanoma ITMs, and, to Determine tumor:immune interaction in the context of hypoxia using high-dimensional imaging. Using high throughput sequencing technologies, it will determined how tumor and immune cells interact and evolve during the course of transit in ITMs (as these cells become more metabolically and immunologically suppressive as they migrate further from the primary site). The clonal evolution analysis of tumor cells through and pimonidazole-enabled single cell RNA-sequencing will be used to identify transcriptomic changes in tumor, immune, and stromal cells correlated with hypoxia exposure.

Arms & Interventions

Arms

: Pimonidazole

Single dose of 0.5 gm/m^2 of pimonidazole (approximately 13 mg/kg)

Interventions

Drug: - Pimonidazole

Pimonidazole is not used with therapeutic intent, and has a non-hazardous designation. It has been widely used for in-vivo evaluation of intratumor hypoxia, and patients will take PO pimonidazole before the scheduled biopsy. Patients receive an oral dose of pimonidazole, a safe chemical tracer up to 24 hours prior to biopsy. Pimonidazole allows for true hypoxia staining; pimonidazole binds hypoxic proteins covalently, creating an antigen that facilitates the imaging, flow cytometry, and scRNA-seq experiments proposed. Pimonidazole has been previously used in patients and is safe and well tolerated, without anticipated adverse events.

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.

UPMC Hillman Cancer Center, Pittsburgh, Pennsylvania

Status

Recruiting

Address

UPMC Hillman Cancer Center

Pittsburgh, Pennsylvania, 15232

Site Contact

Amy Rose, RN, BSN

[email protected]

412-647-8587