Correlating Early FDG PET/CT and ctDNA in Immune Checkpoint Inhibitor (ICI)-Treated Melanoma Patients

Correlation Between Early Interval 18F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography (PET/CT) and Circulating Tumor DNA (ctDNA) in Advanced Melanoma Patients Treated With Immune Checkpoint Inhibitors

The purpose of this research study is to determine if analysis of PET/CT scans and testing of blood samples in people with melanoma that has spread in their body can help researchers determine which patients are more or less likely to respond to immunotherapy and are more or less likely to have side effects. 24 participants will be enrolled and be on study until approximately 4 weeks after their first dose of Immune Checkpoint Inhibitor therapy.

Study Overview

• Status: Recruiting
• Conditions: Melanoma; Unresectable Melanoma; Melanoma Stage IV; Melanoma Stage III
• Intervention / Treatment: Diagnostic test: 18F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography

Detailed Description

This is a pilot, prospective, observational study to estimate the degree to which baseline and early interval 18F-FDG PET/CT imaging within 3-4 weeks of ICI therapy initiation can accurately correlate with ctDNA level trends, predict clinical response, onset of immune-related adverse events, and survival outcomes in advanced stage melanoma patients.

Primary Objective

• To determine if early interval response assessment with 18F-FDG PET/CT during initial treatment with ICI therapy at 3-4 weeks correlates with ctDNA level changes in advanced melanoma patients.

Secondary Objectives

• To determine if early interval response assessment with 18F-FDG PET/CT during initial treatment with ICI therapy at 3-4 weeks predicts clinical efficacy at standard disease assessment time points in advanced melanoma patients.
• To assess if early interval response assessment with 18F-FDG PET/CT predicts development of clinical irAEs in advanced melanoma patients.
• To assess if early interval response assessment with 18F-FDG PET/CT and ctDNA level predicts progression-free survival (PFS) in advanced melanoma patients.
• To assess if early interval response assessment with 18F-FDG PET/CT and ctDNA level predicts overall survival (OS) in advanced melanoma patients.

• Study Type: Observational
• Enrollment (Estimated): 24

Contacts and Locations

• Study Contact: Name: Cancer Connect; Phone Number: 800-622-8922; Email: clinicaltrials@cancer.wisc.edu

Study Locations

• United States
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • Recruiting
      • University of Wisconsin Hospitals and Clinics (UWHC)
      • Principal Investigator: Steve Cho, MD
      • Principal Investigator: Vincent Ma, MD

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

24 participants with advanced stage III or stage IV melanoma with measurable disease who are deemed appropriate for treatment with ICI therapy.

Description

Inclusion Criteria:

• Willing to provide informed consent.
• Must have an advanced stage III or stage IV melanoma diagnosis for which treatment with ipilimumab, nivolumab, and/or pembrolizumab, either alone or in combination with other ICI therapy, is planned.
• Must be planning to participate in Signatera™ (ctDNA level) monitoring with standard of care laboratory testing routinely obtained for treatment with ICI therapy.
• Individuals at least 18 years of age.
• Women of childbearing potential must be willing to use effective contraception as discussed with their oncologist while participating in this study.
• Willing to comply with all study procedures and be available for the duration of the study.

Exclusion Criteria:

• Not able to receive treatment with ICI therapy
• Use of investigational drugs, biologics, or devices within 30 days prior to enrollment.
• Women who are pregnant, lactating, or planning on becoming pregnant during the study.
• Not suitable for study participation due to other reasons at the discretion of the investigators.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Advanced Melanoma Patients with Immune Checkpoint Inhibitors	Diagnostic test: 18F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography; research scan 3-4 weeks after start of immunotherapy; Other Names: 18F-FDG PET/CT

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in ctDNA level from baseline to 3-4 week after the start of therapy	ctDNA level is monitored per standard of care in this population, data from chart review.	baseline to 3-4 weeks after start of therapy (up to 5 weeks on study)
Change in 18F-FDG PET/CT response from baseline to 3-4 week after the start of therapy	Lesion-level and patient-level 18F-FDG PET/CT response assessment at baseline and at 3-4 weeks after starting ICI therapy reported as SUV max.	baseline to 3-4 weeks after start of therapy (up to 5 weeks on study)
Correlation between ctDNA level change and 18F-FDG PET/CT response from baseline to 3-4 week after the start of therapy	Correlate lesion-level and patient-level 18F-FDG PET/CT response assessment at baseline and at 3-4 weeks after starting ICI therapy with quantitative changes in ctDNA levels at baseline and at 3-4 weeks after starting ICI therapy. Pearson's or Rank's correlation coefficient will be used to measure the baseline measures for ctDNA level trends and PET/CT responses and for those measurements at 3-4 weeks.	baseline to 3-4 weeks after start of therapy (up to 5 weeks on study)
Diagnostic Accuracy of ctDNA level trend and PET/CT imaging for predicting growth inhibition as measured by Area under the Curve	Receiver-operator curve analysis will be performed to determine the diagnostic accuracy of ctDNA level trend and PET/CT imaging for predicting growth inhibition (area under the curve).	baseline to 3-4 weeks after start of therapy (up to 5 weeks on study)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR)	Correlate lesion-level and patient-level 18F-FDG PET/CT treatment response assessment at baseline and at 3-4 weeks after starting ICI therapy with clinical response evaluations (RECIST, PERCIST, PECRIT, iRECIST, irRECIST) at 3, 6, 9, and 12 months after the first ICI dose. ORR is Partial Response (PR) plus Complete Response (CR).	up to 12 months after the first ICI dose (approximately 1 year on study)
Disease Control Rate (DCR)	Correlate lesion-level and patient-level 18F-FDG PET/CT treatment response assessment at baseline and at 3-4 weeks after starting ICI therapy with clinical response evaluations (RECIST, PERCIST, PECRIT, iRECIST, irRECIST) at 3, 6, 9, and 12 months after the first ICI dose. DCR is Stable Disease (SD) plus PR plus CR.	up to 12 months after the first ICI dose (approximately 1 year on study)
Change in Standard Uptake Value (SUV) metrics with onset of Immune Related Adverse Events (irAE)	Correlate organ-level FDG uptake and changes from the baseline and early 18F-FDG PET/CT assessment with onset of first, second, and third symptomatic irAE per CTCAE v5.0	up to 12 months after the first ICI dose (approximately 1 year on study)
Progression Free Survival (PFS)	PFS will be summarized using Kaplan-Meier estimates of the median survival times. Point estimates as well as 95% confidence intervals will be provided	up to 3 years after the first ICI dose (approximately 3 years on study)
Correlation Coefficient for 18F-FDG PET/CT response at 3-4 weeks after the start of therapy and PFS	Correlate early 18F-FDG PET/CT treatment response with Progression Free Survival (PFS) as measured from the date of initiation of ICI treatment until the criteria for disease progression is met as defined by RECIST, PECRIT, or death occurs.	up to 3 years after the first ICI dose (approximately 3 years on study)
Correlation Coefficient for ctDNA level at 3-4 weeks after the start of therapy and PFS	Correlate early ctDNA level trends with Progression Free Survival (PFS) as measured from the date of initiation of ICI treatment until the criteria for disease progression is met as defined by RECIST, PECRIT, or death occurs.	up to 3 years after the first ICI dose (approximately 3 years on study)
Overall Survival (OS)	OS will be summarized using Kaplan-Meier estimates of the median survival times. Point estimates as well as 95% confidence intervals will be provided	up to 3 years after the first ICI dose (approximately 3 years on study)
Correlation Coefficient for 18F-FDG PET/CT response at 3-4 weeks after the start of therapy and OS	Correlate early 18F-FDG PET/CT response assessment with Overall Survival (OS) as measured from the date of initiation of ICI treatment until date of death from any cause.	up to 3 years after the first ICI dose (approximately 3 years on study)
Correlation Coefficient for ctDNA level at 3-4 weeks after the start of therapy and OS	Correlate early ctDNA level trends with Overall Survival (OS) as measured from the date of initiation of ICI treatment until date of death from any cause.	up to 3 years after the first ICI dose (approximately 3 years on study)

Collaborators and Investigators

• Sponsor: University of Wisconsin, Madison
• Investigators: Principal Investigator: Vincent Ma, MD, University of Wisconsin, Madison

Study record dates

Study Major Dates

• Study Start (Actual): January 30, 2024
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): January 1, 2029

Study Registration Dates

• First Submitted: December 27, 2023
• First Submitted That Met QC Criteria: December 27, 2023
• First Posted (Actual): January 10, 2024

Study Record Updates

• Last Update Posted (Actual): January 20, 2026
• Last Update Submitted That Met QC Criteria: January 15, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: FDG; circulating tumor DNA; ICI
• 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; Diagnostic Techniques and Procedures; Diagnosis; Tomography; Diagnostic Imaging; Radiography; Image Interpretation, Computer-Assisted; Radiographic Image Enhancement; Image Enhancement; Photography; Tomography, X-Ray; Tomography, X-Ray Computed
• Other Study ID Numbers: 2023-1089; A534260 (Other Identifier: UW Madison); UW23077 (Other Identifier: UWCCC); Protocol Version 2/12/2024 (Other Identifier: UW Madison); NCI-2023-11059 (Registry Identifier: NCI Trial ID)

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: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No