NCT04658303 · Yana Najjar
Evolution of Metabolic and Immune Dysfunction in In-transit Melanoma
What this study is about
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.
View original scientific description
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.
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.
Primary outcome measures
Immunometabolic profiling
Time frame: At baseline
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.
Tumor cell metabolism
Time frame: At baseline
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).
Imaging of individual ITM stations
Time frame: At baseline
CODEX imaging will be conducted on sections from each station using extensive phenotyping panels.
hypoxia exposure analyses
Time frame: At baseline
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.
Who can participate
This study lists these criteria on ClinicalTrials.gov. A study coordinator reviews eligibility during screening — this page does not determine whether you qualify.
Inclusion criteria
- 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.
Exclusion criteria
- 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.
Where
- Pittsburgh, Pennsylvania
Collaborators
Hypoxyprobe
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Frequently asked questions
What is a clinical trial?
A clinical trial is a research study that tests new medical treatments, drugs, devices, or procedures to determine their safety and effectiveness. Trials are carefully designed and monitored to protect participants while advancing medical knowledge.
Is it safe to participate?
Clinical trials follow strict safety guidelines and ethical standards. Trials must be reviewed and approved, and participants are closely monitored by medical professionals throughout the study. You can withdraw at any time if you choose.
Will I be compensated?
Many clinical trials offer compensation for your time, travel expenses, and inconvenience. The specific compensation varies by study and will be discussed during the screening process. All study-related medical care is typically provided at no cost to participants.
Will I receive a placebo instead of treatment?
When effective treatment exists, participants typically receive either the standard treatment plus the study intervention, or the standard treatment plus placebo. You would not be denied effective care. Placebos are primarily used when no proven treatment is available, or in addition to standard care. Your trial consent form will clearly explain what treatments you may receive.
Can I leave a trial if I change my mind?
Absolutely. Participation in clinical trials is completely voluntary. You have the right to withdraw from the study at any time, for any reason, without penalty or loss of benefits to which you are otherwise entitled.
How long does a clinical trial last?
Trial duration varies widely depending on the study design and purpose. Some trials last just a few weeks, while others may continue for months or years. The study coordinator will provide specific timeline information during your screening call.
Data: ClinicalTrials.gov · synced Jun 11, 2026 · Source of record for eligibility and locations