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

NCT06828263 | Recruiting

• 1 other identifier: CEMEN 2024-06
• Study Type: observational
• Target: 130
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Prostate Cancer Metastatic Disease

Keywords

Prostate cancer metastatic disease; [177Lu]Lu-PSMA; metastatic castration-resistant prostate cancer; mCRPC; LuPSMA-SPECT/CT imaging

Outcome Measures

Primary Outcomes (1)

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

  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 Outcomes (6)

• Validate prognostic value of interim PSMA-PET/CT performed at 10 weeks after initiation of [177Lu]Lu-PSMA

  From treatment initiation to at least 12 months after treatment initiation

• To compare cost-effectiveness of SPECT/CT versus PET/CT treatment response strategy

  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

  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

  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

  From treatment initiation to at least 12 months after treatment initiation

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients from the investigator's department only

You may qualify if:

• 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

You may not qualify if:

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

Sponsors & Collaborators

• LMU Klinikum: collaborator
• Gustave Roussy, Cancer Campus, Grand Paris: collaborator
• University Hospital, Grenoble: lead
• Johns Hopkins University: collaborator

Study Sites (1)

CHU Grenoble Alpes

Grenoble, 38053, France

RECRUITING

Related Publications (7)

• Gafita A, Djaileb L, Rauscher I, Fendler WP, Hadaschik B, Rowe SP, Herrmann K, Calais J, Rettig M, Eiber M, Weber M, Benz MR, Farolfi A. Response Evaluation Criteria in PSMA PET/CT (RECIP 1.0) in Metastatic Castration-resistant Prostate Cancer. Radiology. 2023 Jul;308(1):e222148. doi: 10.1148/radiol.222148.

  PMID: 37432081 RESULT

• Pathmanandavel S, Crumbaker M, Ho B, Yam AO, Wilson P, Niman R, Ayers M, Sharma S, Hickey A, Eu P, Stockler M, Martin AJ, Joshua AM, Nguyen A, Emmett L. Evaluation of 177Lu-PSMA-617 SPECT/CT Quantitation as a Response Biomarker Within a Prospective 177Lu-PSMA-617 and NOX66 Combination Trial (LuPIN). J Nucl Med. 2023 Feb;64(2):221-226. doi: 10.2967/jnumed.122.264398. Epub 2022 Aug 25.

  PMID: 36008120 RESULT

• John N, Pathmanandavel S, Crumbaker M, Counter W, Ho B, Yam AO, Wilson P, Niman R, Ayers M, Poole A, Hickey A, Agrawal S, Perkins G, Kallinen A, Eslick E, Stockler MR, Joshua AM, Nguyen A, Emmett L. 177Lu-PSMA SPECT Quantitation at 6 Weeks (Dose 2) Predicts Short Progression-Free Survival for Patients Undergoing 177Lu-PSMA-I&T Therapy. J Nucl Med. 2023 Mar;64(3):410-415. doi: 10.2967/jnumed.122.264677. Epub 2022 Sep 8.

  PMID: 36215568 RESULT

• Kendrick J, Francis RJ, Hassan GM, Rowshanfarzad P, Ong JS, McCarthy M, Alexander S, Ebert MA. Prognostic utility of RECIP 1.0 with manual and AI-based segmentations in biochemically recurrent prostate cancer from [68Ga]Ga-PSMA-11 PET images. Eur J Nucl Med Mol Imaging. 2023 Nov;50(13):4077-4086. doi: 10.1007/s00259-023-06382-2. Epub 2023 Aug 8.

  PMID: 37550494 RESULT

• Shagera QA, Karfis I, Kristanto P, Spyridon S, Diamand R, Santapau A, Peltier A, Roumeguere T, Flamen P, Artigas C. PSMA PET/CT for Response Assessment and Overall Survival Prediction in Patients with Metastatic Castration-Resistant Prostate Cancer Treated with Androgen Receptor Pathway Inhibitors. J Nucl Med. 2023 Dec 1;64(12):1869-1875. doi: 10.2967/jnumed.123.265874.

  PMID: 37770114 RESULT

• Gafita A, Rauscher I, Weber M, Hadaschik B, Wang H, Armstrong WR, Tauber R, Grogan TR, Czernin J, Rettig MB, Herrmann K, Calais J, Weber WA, Benz MR, Fendler WP, Eiber M. Novel Framework for Treatment Response Evaluation Using PSMA PET/CT in Patients with Metastatic Castration-Resistant Prostate Cancer (RECIP 1.0): An International Multicenter Study. J Nucl Med. 2022 Nov;63(11):1651-1658. doi: 10.2967/jnumed.121.263072. Epub 2022 Apr 14.

  PMID: 35422442 RESULT

• Sartor O, de Bono J, Chi KN, Fizazi K, Herrmann K, Rahbar K, Tagawa ST, Nordquist LT, Vaishampayan N, El-Haddad G, Park CH, Beer TM, Armour A, Perez-Contreras WJ, DeSilvio M, Kpamegan E, Gericke G, Messmann RA, Morris MJ, Krause BJ; VISION Investigators. Lutetium-177-PSMA-617 for Metastatic Castration-Resistant Prostate Cancer. N Engl J Med. 2021 Sep 16;385(12):1091-1103. doi: 10.1056/NEJMoa2107322. Epub 2021 Jun 23.

  PMID: 34161051 RESULT

Central Study Contacts

Loïc DJAÏLEB, PU-PH

CONTACT

04 76 76 54 55; ldjaileb@chu-grenoble.fr

Marine FAURE

CONTACT

04 76 76 68 72; MFaure6@chu-grenoble.fr

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Target Duration: 12 Months
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 10, 2025
• First Posted: February 14, 2025
• Study Start: August 1, 2023
• Primary Completion (Estimated): June 1, 2043
• Study Completion (Estimated): December 1, 2043
• Last Updated: December 26, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)