ctDNA for Risk Stratification in Melanoma

The Value of Circulating Tumour DNA in Risk Stratification in Melanoma

This study examines circulating tumor DNA (ctDNA) as a biomarker in patients with primary melanoma, prior to surgical excision. The hypothesis is that ctDNA may be detectable in pre-operative blood samples from patients with high-risk primary melanoma, potentially providing a baseline measurement for future disease monitoring.

Study Overview

• Status: Active, not recruiting
• Conditions: Melanoma (Skin Cancer)

Detailed Description

This prospective, single-institution study recruits patients presenting with suspected primary melanoma at the department of Plastic and Reconstructive Surgery, Herlev and Gentofte University Hospital, Copenhagen University. Patients with invasive melanoma of stage T3a or higher, or with sentinel node metastasis (N1a or higher), and no distant metastasis (M0) will be selected for final analysis.

Pre-operative blood samples are collected prior to surgical excision. Plasma is harvested and stored. Tumor tissue from excised melanomas is analyzed using next-generation sequencing (NGS, Oncomine Tumor Mutational Load panel) to determine the mutational profile. For patients with targetable mutations, corresponding plasma samples are analyzed for ctDNA using either digital droplet PCR (ddPCR) or plasma NGS depending on the local availability of validated mutation-specific assays.

Enrollment will take place from September 2021 to December 2022, with laboratory analyses expected to be completed in 2025 and final analysis completed by May 2026. This study shares the ethical approval (H-18008586) and biobank infrastructure with a parallel study investigating ctDNA for detection of melanoma recurrence (NCT06246227).

• Study Type: Observational
• Enrollment (Actual): 296

Contacts and Locations

Study Locations

• Denmark
  • Herlev, Denmark, 2730
    • Dept. of Plastic and Reconstructive Surgery, Herlev and Gentofte University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

All patients presenting with suspicion of primary melanoma at the department of Plastic and Reconstructive Surgery, Herlev and Gentofte University Hospital, in the inclusion period.

Description

Inclusion Criteria:

• Age 18 years or older
• Clinical suspicion of primary cutaneous melanoma
• Presenting at the Department of Plastic and Reconstructive Surgery, Herlev and Gentofte University Hospital
• Able to provide written informed consent

Exclusion Criteria:

• Age less than 18 years
• Pregnancy
• Inability to provide written informed consent

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
Primary Melanoma Patients; Patients presenting with suspected primary melanoma prior to surgical excision. Patients that are shown to have invasive melanoma of stage T3a or higher, OR sentinel node metastasis N1a or higher OR distant metastasis M1 or higher, and a targetable tumor mutation in tissue sample are selected for ctDNA analysis.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Detectable Circulating Tumor DNA (ctDNA) in Pre-operative Plasma as Assessed by ddPCR or Targeted NGS	A venous blood sample is drawn before surgical excision of the primary melanoma. Plasma is isolated and analyzed for the presence of the same cancer-specific DNA mutation previously identified in the patient's tumor tissue. Two methods are used depending on mutation type: digital droplet PCR (ddPCR, Bio-Rad QX200) for BRAF V600E mutations, or targeted next-generation sequencing (Oncomine Tumor Mutational Load panel, Ion Torrent S5) for other mutations. A sample is classified as "detected" if at least one confirmed mutant DNA copy is identified by ddPCR, or if the tumor-specific variant is present above the assay detection threshold by NGS. The outcome is reported as the number of participants with detected ctDNA out of the total number of participants analyzed.	At a single time point prior to surgical excision of the primary melanoma, at the patient's initial clinical presentation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Detectable ctDNA by Tumor Stage as Assessed by ddPCR or Targeted NGS	The number of participants with detectable ctDNA is reported separately for each AJCC 8th edition stage group (IIB, IIC, IIIA, IIIB, IIIC) represented in the study patient cohort. This exploratory outcome evaluates whether more advanced tumor stage is associated with a higher likelihood of ctDNA detection. Stage is determined from pathological T-classification (based on Breslow thickness and ulceration) and sentinel node status according to AJCC Cancer Staging Manual, 8th edition.	At a single time point prior to surgical excision of the primary melanoma, at the patient's initial clinical presentation.

Collaborators and Investigators

• Sponsor: Herlev and Gentofte Hospital
• Collaborators: Danish Cancer Society; Danish Cancer Research Foundation; DCCC ctDNA Research Center; CAG in Cancer immunotherapy
• Investigators: Study Director: Lisbet R Hölmich, MD, DMSc, Professor, Dept. of Plastic and Reconstructive Surgery, Herlev and Gentofte University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): September 10, 2021
• Primary Completion (Actual): May 20, 2025
• Study Completion (Estimated): May 3, 2026

Study Registration Dates

• First Submitted: March 31, 2026
• First Submitted That Met QC Criteria: April 11, 2026
• First Posted (Actual): April 15, 2026

Study Record Updates

• Last Update Posted (Actual): April 15, 2026
• Last Update Submitted That Met QC Criteria: April 11, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: biomarker; melanoma; stratification; ngs; ctdna; ddpcr
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Skin Diseases; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Nevi and Melanomas; Skin Neoplasms; Skin and Connective Tissue Diseases; Melanoma
• Other Study ID Numbers: H-18008586-S2

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No