Evolution of Metabolic and Immune Dysfunction in In-transit Melanoma

NCT04658303 | Recruiting DMC FDA Drug

• 1 other identifier: HCC 20-263
• Study Type: observational
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Melanoma

Keywords

immune dysfunction; metabolic dysfunction; Melanoma in-transit metastases (ITMs); tumor microenvironment (TME)

Outcome Measures

Primary Outcomes (4)

• Immunometabolic profiling

  Immunometabolic profiling of individual microenvironments in ITMs (in-transit metastases) using flow cytometry via T cell subsets, markers of activation/exhaustion, and metabolic insufficiency (mitochondrial mass, glucose uptake capacity, and hypoxia by pimonidazole staining.

  At baseline

• Tumor cell metabolism

  Tumor cells metabolism of ITMs (in-transit metastases) will be profiled using the Seahorse flux analyzer to measure oxygen consumption rate (OCR) and extracellular acidification rate (ECAR).

  At baseline

• Imaging of individual ITM stations

  CODEX imaging will be conducted on sections from each station using extensive phenotyping panels.

  At baseline

• hypoxia exposure analyses

  Akoya Biosciences' CODEX analysis suite and custom ImageJ plugins will be used to determine proximity of cells to one another, coincidence with hypoxic areas, and accumulation of regulatory/dysfunctional populations.

  At baseline

Secondary Outcomes (5)

• Whole exome sequencing of tumor cells

  At baseline

• Clonal evolution analysis of individual ITMs

  At baseline

• Cellular heterogeneity and transcriptomic state

  At baseline

• TCR clonotype and trajectory analysis

  At baseline

• Tumor transcriptomic states

  At baseline

Study Arms (1)

Pimonidazole

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

Drug: Pimonidazole

Interventions

Pimonidazole DRUG

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.

Pimonidazole

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients with a histological diagnosis of melanoma

You may qualify if:

• Be willing and able to provide written informed consent for the trial.
• Be ≥ 18 years of age on day of signing informed consent.
• 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.
• Cutaneous, mucosal or uveal melanoma are permitted.
• Patients may be on treatment or treatment naïve.
• Female patients of childbearing potential must have a negative urine or serum pregnancy test within 7 days from the time of pimonidazole administration.

You may not qualify if:

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

Sponsors & Collaborators

• Yana Najjar: lead
• Hypoxyprobe: collaborator

Study Sites (1)

UPMC Hillman Cancer Center

Pittsburgh, Pennsylvania, 15232, United States

RECRUITING

Biospecimen

Retention: SAMPLES WITHOUT DNA

Biopsy of 2-5 lesions from each individual patient. 1-3 core or punch biopsies are permitted per lesion Blood will be collected the time of biopsy for correlative analyses (128.5 cc)

MeSH Terms

Conditions

Melanoma; Immune System Diseases

Interventions

pimonidazole

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Yana Najjar, MD

  UPMC Hillman Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Amy Rose, RN, BSN

CONTACT

412-647-8587; kennaj@upmc.edu

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Professor of Medicine

Study Record Dates

• First Submitted: November 23, 2020
• First Posted: December 8, 2020
• Study Start: February 24, 2021
• Primary Completion (Estimated): March 31, 2028
• Study Completion (Estimated): March 31, 2028
• Last Updated: May 8, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)