Evaluation of Hypoxia in Primary Melanoma

NCT06831071 | Recruiting DMC FDA Drug

• 1 other identifier: HCC 24-102
• Study Type: observational
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

When controlling for tumor present in the Sentinel lymph node (SLN), intranodal hypoxia, as measured by Carbonic Anhydrase IX (CAIX IHC), is associated with worse PFS. This suggests that melanoma tumors may be utilizing deregulated metabolism as a means of propagating themselves to the next station of metastasis. This study aims to prospectively validate previous findings. Patients who are to undergo WLE and SLNB per standard of care (SOC) will be evaluable. It is hypothesized that SLN(s) with increased hypoxia, as measured by pimonidazole staining, will be associated with worse Progression-free Survival (PFS).

Conditions

Melanoma

Keywords

Melanoma in-transit metastases (ITMs); intra-nodal hypoxia; Tumor cell oxidative metabolism (OCR)

Outcome Measures

Primary Outcomes (3)

• Tumor Hypoxia

  Hypoxia (decreased oxygen levels) in the primary tumor in patients with primary melanoma as measured by hypoxyprobe staining in primary tumor through CODEX imaging.

  Day of surgery

• Progression Free Survival

  Median number of months from time of surgery to regression, progression or death, whichever occurs first. Progression is defined as observable disease upon visual evaluation of surgical (anatomical) site.

  Up to 5 years (from date of surgery)

• Sentinel Lymph Node Hypoxia

  Hypoxia (decreased oxygen levels) in the sentinel lymph node (SLN) in patients with primary melanoma as measured by hypoxyprobe staining in primary tumor through CODEX imaging.

  Day of surgery

Secondary Outcomes (1)

• Intra-nodal - intra-tumoral hypoxia correlation

  Day of surgery

Study Arms (1)

Pimonidazole

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

Drug: Pimonidazole

Interventions

Pimonidazole DRUG

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.

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:

• Must be willing and able to provide written informed consent for the study.
• Must have histologically confirmed melanoma for which a Sentinel Lymph Node Biopsy (SLNB) is indicated per the treating physician.
• Cutaneous or mucosal melanoma is permitted.
• Female patients of childbearing potential must have a negative urine or serum pregnancy test within 7 days from the time of pimonidazole administration.
• Female subjects of childbearing potential must not be pregnant or breastfeeding. Female subjects will be considered of non-reproductive potential if they:
• are postmenopausal (defined as at least 12 months with no menses without an alternative medical cause; in women \< 45 years of age a high follicle stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a post-menopausal state in women not using hormonal contraception or hormonal replacement therapy. In the absence of 12 months of amenorrhea, a single FSH measurement is insufficient.
• have had a hysterectomy and/or bilateral oophorectomy, bilateral salpingectomy or bilateral tubal ligation/occlusion, at least 6 weeks prior to screening.
• have a congenital or acquired condition that prevents childbearing.
• Female and male subjects of reproductive potential must agree to avoid becoming pregnant or impregnating a partner, respectively, while receiving study drug and 1 week after the dose of study drug for females and 2 weeks for males by complying with one of the following:
• practice abstinence from heterosexual activity
• use (or have their partner use) acceptable contraception during heterosexual activity.
• Adequate hematologic function: white blood cells (WBC) ≥ 2,500/μL, platelet count ≥ 100,000/μL, hemoglobin ≥ 8.0 g/dL
• Adequate renal function: serum creatinine ≤ 2.0 mg/dL
• Adequate hepatic function: serum alkaline phosphatase, bilirubin, and ALT ≤ twice the institutional upper limit of normal

You may not qualify if:

• Subjects with known chronic immunosuppression (such as biologic agents like infliximab, mycophenolate, methotrexate, prednisone \> 20 mg daily).
• Severe septicemia or severe infection in the 4 weeks prior to study entry.
• History of previous neuropathy from chemotherapy or other causes not related to cancer.
• Pregnant subjects or breastfeeding subjects. (Note: A pregnancy test will be administered within 7 days prior to the administration of pimonidazole to female subjects of childbearing potential enrolled in the study.)
• Subjects with (ECOG) Performance scale of 4 - subjects unable to perform self-care.
• Subjects who have received an investigational new drug 6 half-lives or two weeks prior to enrollment in this study, whichever is shorter.

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

Slides of tumor tissue and sentinel lymph node biopsy obtained at the time of surgery. Peripheral blood and Stool collection at the time screening for future correlative studies.

MeSH Terms

Conditions

Melanoma

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 M Najjar, MD

  UPMC Hillman Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Danielle L Bednarz, RN, BSN

CONTACT

4126231191; bednarzdl@upmc.edu

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: February 13, 2025
• First Posted: February 17, 2025
• Study Start: April 9, 2025
• Primary Completion (Estimated): March 31, 2027
• Study Completion (Estimated): March 31, 2027
• Last Updated: May 8, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)