Liquid Biopsy Under PSMA Radioligand Therapy (LOOPS)

Liquid Biopsy as a Biomarker in Patients Treated With PSMA Radioligand Therapy

Prostate cancer is the second most common cause of cancer death in men worldwide. After exhausting guideline-compliant therapies or in accordance with the approval of 177Lu-PSMA-617 (Pluvicto®), patients with metastatic castration-resistant prostate cancer (mCRPC) can be offered radioligand therapy (RLT) that targets the prostate-specific membrane antigen (PSMA). Despite an initially high response rate to PSMA-RLT, the disease often progresses rapidly again. The underlying mechanisms are still poorly understood.

Liquid biopsy (LBx) involves the collection and analysis of body fluids, particularly blood. Its major advantage compared to a tissue sample is its non-invasive nature, allowing for multiple samplings, as well as the examination of more than just a single punctured lesion. Among other things, circulating tumor DNA (ctDNA) can be detected in the blood.

The aim of this study is to apply LBx before, during, and after PSMA-RLT in patients with mCRPC to determine prognostic factors before therapy and to assess the value of LBx in evaluating treatment response. Furthermore, LBx will be used to gather information on the course of potential tumor heterogeneities and to determine resistance mechanisms against PSMA-RLT.

To this end, patients receiving PSMA-RLT will be enrolled in the study at three sites (University Hospital Wuerzburg, University Hospital Augsburg, Klinikum rechts der Isar Munich). The evaluation of clinical and imaging parameters will be carried out centrally at the University Hospital Wuerzburg, while the analysis of LBx will be performed at the University Hospital Augsburg.

Study Overview

• Status: Recruiting
• Conditions: Prostate Cancer; Prostate Cancer Metastatic Castration-Resistant

• Study Type: Observational
• Enrollment (Estimated): 100

Contacts and Locations

• Study Contact: Name: Kerstin Michalski, MD; Phone Number: +4993120135931; Email: michalski_k@ukw.de
• Study Contact Backup: Name: Rainer Claus, Prof.; Email: Rainer.Claus@uk-augsburg.de

Study Locations

• Germany
  • Augsburg, Germany
    • Recruiting
    • University hospital Wuerzburg - Department of Nuclear Medicine
    • Contact: Constantin Lapa, Prof.; Phone Number: 0049 821 400-2050; Email: Constantin.Lapa@uk-augsburg.de
    • Contact: Email: Constantin.Lapa@uk-augsburg.de
    • Principal Investigator: Constantin Lapa, Prof.
  • München, Germany
    • Recruiting
    • TUM Klinikum rechts der Isar - Department of Nuclear medicine
    • Contact: Matthias Eiber, Prof.; Phone Number: +49 89 4140 2971; Email: Matthias.Eiber@mri.tum.de
    • Contact: Email: Matthias.Eiber@mri.tum.de
    • Principal Investigator: Matthias Eiber, Prof.
  • Wuerzburg, Germany
    • Recruiting
    • University hospital Wuerzburg - Department of Nuclear Medicine
    • Contact: Kerstin Michalski, MD; Phone Number: +4993120135931; Email: michalski_k@ukw.de
    • Contact: Email: michalski_k@ukw.de
    • Principal Investigator: Kerstin Michalski, MD

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

Patients with metastatic castration-resistant prostate cancer undergoing PSMA radioligand therapy

Description

Inclusion Criteria:

• Patients with mCRPC eligble for PSMA RLT
• In-lable use for PSMA RLT
• PSMA PET/CT not older than 8 weeks prior to first cycle of PSMA RLT
• One previous line of antiandrogen receptor pathway treatment and one previous line of taxan based therapy
• Age ≥ 18 years
• Written informed consent
• Sufficient knowledge of the German language or presence of a translator

Exclusion Criteria:

• Unwilling to adhere to study procedures
• Missing interdisciplinary tumor conference advise for PSMA RLT

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Prognostic value of LBx (precisely ctDNA) before PSMA RLT	identification of responders (partial response and stable disease)/non-responders (progressive disease) after 2 cycles of PSMA RLT, time-to-event analysis that could provide insights into overall survival or progression-free survival based on ctDNA level	16-18 weeks
Comparison of response assessment using LBx with biochemical response (PSA) after 2 cycles of PSMA RLT		16-18 weeks
Comparison of response assessment using LBx with imaging-based response (PSMA PET/CT) after 2 cycles of PSMA RLT		16-18 weeks

Collaborators and Investigators

• Sponsor: Wuerzburg University Hospital
• Collaborators: German Research Foundation; Technical University of Munich; University Hospital Augsburg
• Investigators: Principal Investigator: Kerstin Michalski, MD, University hospital Wuerzburg - Department of Nuclear Medince; Principal Investigator: Rainer Claus, Prof., University hospital Augsburg - Internal Medicine II

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2024
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): August 1, 2028

Study Registration Dates

• First Submitted: July 28, 2025
• First Submitted That Met QC Criteria: August 8, 2025
• First Posted (Actual): August 12, 2025

Study Record Updates

• Last Update Posted (Actual): August 12, 2025
• Last Update Submitted That Met QC Criteria: August 8, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Keywords: mCRPC; PSMA; cfDNA; liquid biopsy; radioligand therapy
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Prostatic Diseases; Male Urogenital Diseases; Prostatic Neoplasms
• Other Study ID Numbers: GZ: MI 3238/1-1

Drug and device information, study documents

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