MelanomaNCT04658303
Evolution of Metabolic and Immune Dysfunction in In-transit Melanoma
An observational study of Melanoma, run by Yana Najjar at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Melanoma
- What is being tested?
- Pimonidazole
- Type of treatment
- Pill or oral medicine
- How many people
- 20 participants
- Where
- 1 siteUnited States
- Study dates
- 24 Feb 2021to 31 Aug 2029
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Patients with a histological diagnosis of melanoma
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
UPMC Hillman Cancer Center
Pittsburgh, Pennsylvania, 15232
Amy Rose, RN, BSN, 412-647-8587, kennaj@upmc.edu
Yana Najjar, MD
About this study
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.
Read the detailed description
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.
- Conditions
- Melanoma
- Being tested
- Pimonidazole
- Keywords
- immune dysfunction, metabolic dysfunction, Melanoma in-transit metastases (ITMs), tumor microenvironment (TME)
- Medical subject headings
- Melanoma, Immune System Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PimonidazoleDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| Pimonidazole | Single dose of 0.5 gm/m^2 of pimonidazole (approximately 13 mg/kg) Receives: Drug: Pimonidazole |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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).
Measured: At baseline
Imaging of individual ITM stations
CODEX imaging will be conducted on sections from each station using extensive phenotyping panels.
Measured: 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.
Measured: At baseline
Secondary outcomes (5)
Whole exome sequencing of tumor cells
Whole exome sequencing will be performed to identify mutations in tumor cells isolated from each lesion. Analysis will be in an 'intrapatient' manner as a function of distance from the primary site.
Measured: At baseline
Clonal evolution analysis of individual ITMs
Mutations will be used to construct trees revealing clonal representation and diversity at each station. The goal is to determine how migration away from the primary site affects a tumor's heterogeneity in terms of tumor cells.
Measured: At baseline
Cellular heterogeneity and transcriptomic state
The composition of each ITM tumor microenvironment will be analyzed using dimension reduction strategies, in collaboration with a bioinformatics core. Each biopsy sample will be sequenced simultaneously but hashed separately, allowing all ITMs to be compared in one run. Clusters will be identified using lineage-defining genes and then transcriptomic states identified within each cluster.
Measured: At baseline
TCR clonotype and trajectory analysis
5' scRNAseq will be used for identification of TCR sequences to identify individual T cell clones. Clonotypes will be revealed in each lesion, and diffusion pseudotime analyses will be employed within each ITM and between ITMs to determine differentiation states of various T cell subsets. It is thought that distant lesions will harbor more terminally differentiated T cells.
Measured: At baseline
Tumor transcriptomic states
Analysis of hypoxia exposure for each cell using unique pimonidazole CITE-seq strategy also allows for the a. As hypoxia promotes the terminal differentiation of T cells, it is expected that distant ITMs will harbor more hypoxic cells and that terminally differentiated T cells will experience higher levels of hypoxia.
Measured: At baseline
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Dec 2020
- Study start24 Feb 2021
- Primary completion31 Aug 2029 (estimated)
- Study completion31 Aug 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for MelanomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Yana Najjar
- Sponsor type
- University, hospital or other
- Collaborators
- Hypoxyprobe
- Responsible party
- Sponsor-investigator, Yana Najjar, University of Pittsburgh
- Investigators
- Yana Najjar, MD, Principal investigator, UPMC Hillman Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04658303
- Sponsor's protocol ID
- HCC 20-263
- Status last verified
- Jun 2026
- First submitted
- 23 Nov 2020
- Last updated
- 11 Jun 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 11 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evolution of Metabolic and Immune Dysfunction in In-transit Melanoma
- ClinicalTrials.gov ID
- NCT04658303
- Acronym / sponsor ID
- HCC 20-263
- Conditions
- Melanoma
- Keywords
- immune dysfunction, metabolic dysfunction, Melanoma in-transit metastases (ITMs), tumor microenvironment (TME)
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- Yana NajjarUniversity, hospital or other
- Collaborators
- Hypoxyprobe
- Study start
- 24 Feb 2021 (actual)
- Primary completion
- 31 Aug 2029 (estimated)
- Study completion
- 31 Aug 2029 (estimated)
- First posted
- 8 Dec 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Pimonidazole | – | Drug: PimonidazoleSingle dose of 0.5 gm/m^2 of pimonidazole (approximately 13 mg/kg) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Patients with a histological diagnosis of melanoma
Key inclusion criteria (6 listed)
- 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.
Key exclusion criteria (3 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PimonidazolePimonidazole 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. | Drug | Pimonidazole |
Primary outcome
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.
5 secondary outcomes
Whole exome sequencing of tumor cells
Time frame: At baseline
Clonal evolution analysis of individual ITMs
Time frame: At baseline
Cellular heterogeneity and transcriptomic state
Time frame: At baseline
TCR clonotype and trajectory analysis
Time frame: At baseline
Tumor transcriptomic states
Time frame: At baseline
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Jun 2026.
- Individual participant dataSharing planned: No
Related trials for Melanoma
RecruitingPhase 1/2
Study of INBRX-106 and INBRX-106 in Combination With Pembrolizumab (Keytruda®) in Subjects With Locally Advanced or Metastatic Solid Tumors (Hexavalent OX40 Agonist)
Solid Tumor, Non-Small Cell Lung Cancer
RecruitingPhase 1
IL-17 Blockade to Decrease irAEs (REPLAY)
Metastatic Melanoma
Enrolling by invitationObservational study
Natural History Study of Early Life Exposures in Agriculture (ELEA)
Prostate Cancer, Leukemia
RecruitingPhase 1
A Feasibility Study Utilizing Immune Recall to Increase Response to Checkpoint Therapy
Melanoma
Active, not recruitingPhase 1/2
A Study of Dapansutrile Plus Pembrolizumab in Patients With PD-1 Refractory Advanced Melanoma
Melanoma
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Yana Najjar, MD principal investigator
UPMC Hillman Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Melanoma, run by Yana Najjar at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 11 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Danielle Bednarz, RN, BSN (412-623-1191, bednarzdl@upmc.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Immunometabolic profiling (time frame: At baseline). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Jun 2026.