Prospective Evaluation of Imaging Response Biomarkers During [177Lu]Lu-PSMA in Metastatic Castration-resistant Prostate Cancer
Trial ID: NCT06828263
Status: RECRUITING
Study type: OBSERVATIONAL
Start date: 2023-08-01
Completion date: 2043-12
Sponsor: University Hospital, Grenoble
Collaborators: Johns Hopkins University; LMU Klinikum; Gustave Roussy, Cancer Campus, Grand Paris
Conditions: Prostate Cancer Metastatic Disease
Locations: CHU Grenoble Alpes
Countries: France
Enrollment: 130
Age range: 18 Years - None
Sex: MALE

Summary:
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.

Eligibility criteria:
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.

Outcomes:
Confirm prospectively the prognostic value of post-therapy SPECT/CT imaging for response evaluation during [177Lu]Lu- PSMA