Prospective Evaluation of Imaging Response Biomarkers During [177Lu]Lu-PSMA in Metastatic Castration-resistant Prostate Cancer (68Ga-PSMA)

December 18, 2025 updated by: University Hospital, Grenoble

Lutetium-177 (177Lu) prostate-specific membrane antigen (177Lu-PSMA) is a radiolabelled small-molecule inhibitor that binds with high affinity to PSMA and delivers β particle radiation. [177Lu]Lu-PSMA-617 (Pluvicto) was approved by the U.S. Food and Drug administration (FDA) in patients with late-stage, PSMA positive metastatic castration-resistant prostate cancer (mCRPC) based on the results from the phase 3 VISION trial [1].

Early identification of tumor progression may reduce unnecessary therapy cycles and their associated risk of adverse events as well as reducing costs and improving patient care by initiating an earlier change in treatment towards a possibly more efficacious therapy.

Response Evaluation Criteria In PSMA-imaging (RECIP) version 1.0 is an evidence-based framework to evaluate therapeutic efficacy in metastatic prostate cancer using PSMA-imaging[2,3]. Interim PSMA-PET/CT by RECIP 1.0 criteria performed at 10 weeks after two cycles of PSMA theranostics ([177Lu]Lu-PSMA- 617 or [177Lu]Lu-PSMA-I&T) is prognostic for overall survival[2]. RECIP 1.0 criteria were validated based on overall survival outcome for measuring response in metastatic prostate cancer during androgen receptor-signaling inhibitors[4], as well as in early-stage prostate cancer in patients with biochemical recurrence after initial therapy[5].

Lutetium-177 is a beta therapy that also emits 11% gamma rays, which can be utilised to derive whole-body tomographic images similar to PSMA-PET/CT. Serial Lutetium-177 PSMA-targeted single photon emission tomography/computed tomography [177Lu]Lu-PSMA-SPECT/CT henceforth referred to as LuPSMASPECT/ CT has potential as an imaging response biomarker for 177Lu-PSMA therapy. This principle enables image quantitation and evaluation after every treatment dose. SPECT/CT post [177Lu]Lu-PSMA administration represents a potentially cost-effective alternative to interim PSMA-PET/CT.

Preliminary results have shown a good correlation between changes in LuPSMASPECT/ CT during PSMA theranostics and clinical outcome. LuPSMA-SPECT/CT can provide effective response information as early as 6 weeks after initiation of [177Lu]Lu-PSMA-I&T, i.e. any increase in total tumor volume on SPECT/CT imaging was associated with shorter PSA-PFS (median: 3.7 vs 6.7 months; HR, 2.5; 95% CI 1.5-4.2; p<0.001)[6]. Changes in total tumor volume on 12-week LuPSMASPECT/ CT were also found to be correlated with progression-free survival after [177Lu]Lu-PSMA-I&T[7].

The growing evidence suggesting that LuPSMA-SPECT/CT is a new, early surrogate marker for assessing response to treatment has several potential upsides, including the potential replacement of interim PSMA-PET/CT, therefore costsaving, radiation exposure-saving, and SPECT/CT imaging being more convenient and widely available.

Given that data regarding SPECT/CT-based treatment response monitoring during PSMA theranostics are limited, this study aims to prospectively investigate the role of LuPSMA-SPECT/CT imaging for response evaluation during treatment with [177Lu]Lu-PSMA in mCRPC patients.

Study Overview

Status

Recruiting

Conditions

Study Type

Observational

Enrollment (Estimated)

130

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • France
      • Grenoble, France, 38053
        • Recruiting
        • CHU Grenoble Alpes

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

Patients from the investigator's department only

Description

Inclusion Criteria:

  • Adult aged 18 or older with proven adenocarcinoma of the prostate
  • Diagnosis of progressive metastatic castration-resistant prostate cancer.
  • Progression or intolerance on a novel anti-androgen therapy (i.e. abiraterone, enzalutamide, apalutamide or darolutamide)
  • Prior therapy with at least one taxane-based chemotherapy during the course of prostate cancer or the patient is symptomatic and assessed as unfit for chemotherapy.
  • ECOG Performance status 0 to 2

Exclusion Criteria:

  • Patient opposed to the use of his data for clinical research.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Confirm prospectively the prognostic value of post-therapy SPECT/CT imaging for response evaluation during [177Lu]Lu- PSMA
Time Frame: From treatment initiation to at least 12 months after treatment initiation
Associations between response on 177Lu-PSMA-SPECT with OS, defined as the associations between best overall response achieved on LuPSMA-SPECT/CT at any time during treatment with overall survival. The associations will be considered positive if difference in OS between PD vs nPD is statistically significant (p<0.05) as per Kaplan-Meier analysis (log-rank test).
From treatment initiation to at least 12 months after treatment initiation

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Validate prognostic value of interim PSMA-PET/CT performed at 10 weeks after initiation of [177Lu]Lu-PSMA
Time Frame: From treatment initiation to at least 12 months after treatment initiation
Associations between response on 10-week PSMA-PET/CT with OS. The associations will be considered positive if difference in OS between PD vs nPD or PD vs SD vs PR according to RECIP 1.0 is statistically significant (p<0.05) as per Kaplan-Meier analysis (log-rank test).
From treatment initiation to at least 12 months after treatment initiation
To compare cost-effectiveness of SPECT/CT versus PET/CT treatment response strategy
Time Frame: From treatment initiation to at least 12 months after treatment initiation
Determine clinical significance of performing interim PSMA-PET/CT versus SPECT/CT for treatment response evaluation during [177Lu]Lu- PSMA. Percentage of participants with ≥1 new lesion detected on interim PSMA-PET that is not detected on LuPSMA-SPECT imaging performed at 6 weeks and/or 12 weeks. The interim PSMA-PET will be considered of clinical value if patients with ≥1 new lesion detected only on interim PSMAPET have statistically significant (p<0.05) shorter PFS and/or OS compared to patients without new lesions detected on PSMA-PET and/or LuPSMASPECT, as per Kaplan-Meier analysis (log-rank test).
From treatment initiation to at least 12 months after treatment initiation
Investigate added value of interim [18F]FDG PET to PSMA-PET/CT for response evaluation during [177Lu]Lu-PSMA
Time Frame: From treatment initiation to at least 12 months after treatment initiation
Determine the added value of interim [18F]FDG-PET to PSMA-PET/CT for response evaluation during [177Lu]Lu-PSMA. Presence of new lesion, volume and tumor uptake changing on [18F]FDG-PET performed at 10 weeks. The interim FDG-PET will be considered of clinical value if patients with progression on FDG-PET have statistically significant (p<0.05) shorter PFS and OS compared to patients without new lesions detected on PSMA-PET and/or LuPSMA-SPECT and/or CT images, as per Kaplan-Meier analysis (log-rank test).
From treatment initiation to at least 12 months after treatment initiation
Determine clinical impact of performing interim PSMA-PET/CT versus LuPSMA-SPECT/CT for response evaluation during [177Lu]Lu-PSMA
Time Frame: From treatment initiation to at least 12 months after treatment initiation

Correlations of LuPSMA-SPECT/CT progression-free survival (LuSPECTPFS) with OS. LuSPECT-PFS is defined as the time from treatment initiation to the date of progression on 177Lu-PSMA-SPECT/CT according to RECIP 1.0 criteria or death due to any cause, whichever occurs first [3].

The correlations will be significant if the Spearman coefficient r is higher than 0.6 and p<0.01 [8].
From treatment initiation to at least 12 months after treatment initiation
Inter-reader agreement
Time Frame: From treatment initiation to at least 12 months after treatment initiation
Inter-reader agreement for response evaluation using interim LuPSMA- SPECT/CT and PSMA-PET/CT according to RECIP 1.0.
From treatment initiation to at least 12 months after treatment initiation
Prognostic value of 177Lu-PSMA-SPECT/CT/PSMA PET derived tumor burden quantitative parameters for OS
Time Frame: From treatment initiation to at least 12 months after treatment initiation
Prognostic value of 177Lu-PSMA-SPECT/CT/PSMA PET derived tumor burden quantitative parameters for OS. Total tumor volume, SUVmax, SUVmean and more advanced parameters obtained using artificial intelligence algorithms will be assessed. Association between algorithm predicted outcome with observed outcome will be tested
From treatment initiation to at least 12 months after treatment initiation

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University Hospital, Grenoble

Collaborators

Johns Hopkins University
LMU Klinikum
Gustave Roussy, Cancer Campus, Grand Paris

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

August 1, 2023

Primary Completion (Estimated)

June 1, 2043

Study Completion (Estimated)

December 1, 2043

Study Registration Dates

First Submitted

February 10, 2025

First Submitted That Met QC Criteria

February 10, 2025

First Posted (Actual)

February 14, 2025

Study Record Updates

Last Update Posted (Actual)

December 26, 2025

Last Update Submitted That Met QC Criteria

December 18, 2025

Last Verified

December 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CEMEN 2024-06

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

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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