Evolution of Metabolic and Immune Dysfunction in In-transit Melanoma

NCT ID: NCT04658303

Last Updated: 2025-05-08

Basic Information

• Recruitment Status: RECRUITING
• Total Enrollment: 20 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2021-02-24
• Study Completion Date: 2028-03-31

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.

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

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

Pimonidazole

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

Pimonidazole

Intervention Type: 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.

Interventions

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.

Intervention Type: DRUG

Eligibility 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hypoxyprobe

UNKNOWN

Sponsor Role: collaborator

Yana Najjar

OTHER

Sponsor Role: lead

Responsible Party

Yana Najjar

Assistant Professor of Medicine

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Yana Najjar, MD

Role: PRINCIPAL_INVESTIGATOR

UPMC Hillman Cancer Center

Locations

UPMC Hillman Cancer Center

Pittsburgh, Pennsylvania, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Amy Rose, RN, BSN

Role: CONTACT

kennaj@upmc.edu

412-647-8587

Facility Contacts

Amy Rose, RN, BSN

Role: primary

kennaj@upmc.edu

412-647-8587

Other Identifiers

HCC 20-263

Identifier Type: -

Identifier Source: org_study_id