ctDNA for Early Detection of Recurrence in Melanoma

The Value of Circulating Tumour DNA in Early Detection of Recurrence of Melanoma

This study examines circulating tumor DNA (ctDNA) as a biomarker for early detection of recurrence in high-risk patients, following treatment of primary melanoma. The hypothesis is that ctDNA can provide accurate detection of recurrence or metastasis, at the time of or earlier than current methods, leading to improved management and hopefully prognosis, based on earlier detection.

Study Overview

• Status: Active, not recruiting
• Conditions: Melanoma

Detailed Description

This prospective, single-institution study will recruit patients attending follow-up for primary melanoma with high risk of recurrence, at the department of Plastic and Reconstructive Surgery, Herlev and Gentofte University Hospital, Copenhagen University.

Enrolled patients will undergo regular blood sampling. Samples will be centrifuged and plasma will be harvested and stored. In cases of metastasis or recurrence, tumor tissue samples will be analyzed using NGS to determine their mutational profile. Plasma samples will be analyzed for ctDNA corresponding to identified mutations. If ctDNA is detected, previous samples will be analyzed in reverse sequential order, until no ctDNA is detected.

Follow-up time after inclusion is five years or end of clinical-follow up, with an interim sample and data analysis scheduled for 2024 and final analysis scheduled for 2027-2028.

• Study Type: Observational
• Enrollment (Actual): 467

Contacts and Locations

Study Locations

• Denmark
  • Herlev, Denmark, 2730
    • Detp. of Pastic and Reconstructive Surgery, Herlev Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: N/A

• Sampling Method: Non-Probability Sample

Study Population

All patients followed for high-risk of recurrence, at the department of Plastic and Reconstructive Surgery, Herlev and Gentofte University Hospital, in the inclusion period.

Description

Inclusion Criteria:

• Follow-up for Primary Melanoma, Stages IIB to III and Resected Stage IV

Exclusion Criteria:

• Pregnancy
• Previous history of melanoma

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
High Risk Melanoma Patients; Patients followed-up for Melanoma, Clinical Stages IIB - III and Resected Stage IV

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sensitivity of ctDNA for detection of metastatic disease	By analyzing blood samples of patients diagnosed with recurrence, we will establish the ability of ctDNA to detect known recurrence, and therefore be able to establish the sensitivity of the method.	From enrollment to end of 5-year follow-up
Specificity of ctDNA for detection of metastatic disease	By assuming no ctDNA in healthy individuals and analyzing WBC from buffy-coat to correct for wild-type mutated DNA due to CHIP, we will be able to establish the specificity of the method.	From enrollment to end of 5-year follow-up

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time from detectable ctDNA to clinical og radiological suspicion of recurrence	We will start by analyzing the closest sample to the original suspicion of recurrence. In the event of ctDNA detection, previous samples will be analyzed in reverse sequential order, until no ctDNA is detected. This will allow us to establish a temporal relationship between the ability of ctDNA to detect recurrence and current surveillance methods.	From enrollment to end of 5-year follow-up
Associations between ctDNA detection and quantification, and other biomarkers, including LDH, WBC differential, and HS-CRP	By measuring LDH, WBC Diff. and HS-CRP at every sampling, we will be able to establish the correlation between these currently accepted biomarkers for melanoma-specific survival and ctDNA measurements.	From enrollment to end of 5-year follow-up

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, Clinical Professor, Dept. of Plastic and Reconstructive Surgery, Herlev and Gentofte University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2019
• Primary Completion (Estimated): October 6, 2027
• Study Completion (Estimated): January 1, 2028

Study Registration Dates

• First Submitted: January 30, 2024
• First Submitted That Met QC Criteria: January 30, 2024
• First Posted (Actual): February 7, 2024

Study Record Updates

• Last Update Posted (Actual): March 12, 2024
• Last Update Submitted That Met QC Criteria: March 8, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Detection; Recurrence; Melanoma; ctDNA; NGS; ddPCR
• Additional Relevant MeSH Terms: Pathologic Processes; Skin Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Disease Attributes; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Nevi and Melanomas; Skin Neoplasms; Recurrence; Melanoma
• Other Study ID Numbers: H-18008586

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