Pilot Study of Biomarkers of Response to Immune Checkpoint Blockade in Metastatic Melanoma

This study uses molecular imaging and novel immune monitoring to identify a biomarker of response for melanoma patients receiving immunotherapy with anti-PD-1 immunotherapy. Prior to treatment, FDG and FLT PET/CT will be obtained, together with blood and tumor biopsies from each patient. A follow-up FDG and FLT PET/CT will be obtained, together with blood and tumor biopsies, 10-12 weeks after starting treatment with anti-PD-1 antibody. Additional tumor biopsies and blood samples for immune monitoring will be obtained 4-6 weeks after starting treatment with anti-PD-1 antibody as well as 16-18 weeks after starting anti-PD-1 treatment for patients still receiving anti-PD-1 antibody at that time.

Study Overview

• Status: Completed
• Conditions: Melanoma
• Intervention / Treatment: Other: F-FDG PET/CT

• Study Type: Observational
• Enrollment (Actual): 5

Contacts and Locations

Study Locations

• United States
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • University of Wisconsin Carbone Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: N/A
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Up to 4 metastatic melanoma patients will be recruited from the University of Wisconsin (UW) Carbone Cancer Center (CCC) Melanoma Clinic located in the UW-Hospital and Clinics.

Description

Inclusion Criteria:

• Participants must have a metastatic melanoma diagnosis (stage IV) for which treatment with nivolumab or pembrolizumab, either alone or in combination with other therapies, is planned. No additional laboratory testing is needed for the imaging in this study apart from the standard laboratory testing routinely obtained for treatment with nivolumab or pembrolizumab, either alone or in combination with other therapies.
• Participants must have at least 2 subcutaneous or lymph node melanoma metastases that are 2 cm in greatest diameter and are amenable to being biopsied in clinic without requiring image-guidance.
• Participants must be able to provide informed consent
• Women of childbearing potential must be willing to use effective contraception as discussed with their oncologist while participating in this study.

Exclusion Criteria:

• Not able to receive treatment with either nivolumab or pembrolizumab.
• Women of child-bearing potential must have a negative serum or urine pregnancy test within 7 days of the first study FLT PET/CT and must not be breast feeding for the duration of study participation.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

FLT/PET + biopsy; F-FDG and FLT PET/CT imaging will be obtained prior to anti-cancer treatment and 10-12 weeks after starting treatment with anti-PD-1 antibody.

Other: F-FDG PET/CT; F-FLT PET uses a thymidine analogue that accumulates in proliferating tissue. Proliferating tissue could include malignant lesions or immune cells. In this study, FLT PET/CT will be utilized as a molecular imaging tool to detect immune activation after administration of immune checkpoint blockade with pembrolizumab or nivolumab.; Other Names: 3'-Deoxy-3'-[18F]Fluorothymidine (FLT) PET/CT

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Correlation of baseline of response and antitumor response	To correlate baseline and post-treatment molecular imaging biomarkers of response to immunotherapy with anti-PD-1 with antitumor response based on analysis of the FDG-to-FLT PET/CT ratio in melanoma patients	Anticipated at one-year after last patient enrolled, around Sept 2019

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Correlation of in vivo clonally amplified T cells to FDG PET uptake in melanoma tumors	To correlate in vivo clonally amplified T cells in blood that traffic to tumor to FDG PET uptake in melanoma tumors following treatment with anti-PD-1	Anticipated at one-year after last patient enrolled, around Sept 2019
To correlate histologic and molecular markers of antitumor response to FLT PET uptake in melanoma tumors following treatment with anti-PD-1	To correlate histologic and molecular markers of antitumor response to FLT PET uptake in melanoma tumors following treatment with anti-PD-1	Anticipated at one-year after last patient enrolled, around Sept 2019

Collaborators and Investigators

• Sponsor: University of Wisconsin, Madison
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Mark Albertini, University of Wisconsin, Madison

Publications and helpful links

Helpful Links

• University of Wisconsin Carbone Cancer Center Home

Study record dates

Study Major Dates

• Study Start (Actual): November 2, 2017
• Primary Completion (Actual): June 17, 2022
• Study Completion (Actual): June 17, 2022

Study Registration Dates

• First Submitted: November 22, 2017
• First Submitted That Met QC Criteria: November 22, 2017
• First Posted (Actual): November 29, 2017

Study Record Updates

• Last Update Posted (Actual): July 11, 2022
• Last Update Submitted That Met QC Criteria: July 7, 2022
• Last Verified: July 1, 2022

More Information

Terms related to this study

• Keywords: melanoma; antimelanoma T cells
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Nevi and Melanomas; Melanoma
• Other Study ID Numbers: UW16032; P30CA014520 (U.S. NIH Grant/Contract); A534260 (Other Identifier: UW Madison); SMPH\MEDICINE\HEM-ONC (Other Identifier: UW Madison); 2017-0046 (Other Identifier: Institutional Review Board); Protocol Version 6/19/2019 (Other Identifier: UW Madison)

Drug and device information, study documents

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