A Phase 2 Trial of 61Cu-NU101 PET/CT Compared Against Current Standard-of-care 18F-piflufolastat (Pylarify®) PET/CT.

Official title

A Two Center Phase 2 Trial of 61Cu-noDAGa-PSMA I&T (61Cu-NU101) for Patients With Prostate Cancer

Overview

The purpose of this research is to test whether a new investigational Molecular Imaging (MI) agent called 61Cu-NU101 is equal to or better than a currently used MI agent, Pylarify, for the detection of prostate cancer metastases. 34 participants with biopsy-proven prostate cancer and cancer seen on a Pylarify PET scan will be enrolled in this study. The investigational 61Cu-NU101 PET/CT will be perfromed. If there is a difference between the standard Pylarify exam and the investigational 61Cu-NU101 exam, a biopsy of one lesion that is different between the two exams may be performed.

Detailed description

This is an open, phase 2, two center, non-randomized trial. Total of 34 subjects are planned, based on a statistical analysis to provide 80% power to determine non-inferiority of 61Cu-NU101 as compared to 18F-piflufolastat PET/CT. Each participant will have biopsy-proven prostate cancer visualized on standard-of-care 18F-piflufolastat PET/CT performed within 30 days of trial accrual. If participants have not had a diagnostic quality CT and/or a bone scan within 30 days of trial accrual, then will undergo a diagnostic quality CT and/or bone scan, as needed. Participants will undergo a research 61Cu-NU101 PET/CT, as follows: Each subject will receive a single administration of 61Cu-NU101, followed by PET/CT imaging at 1 and 4 hours. There will be optional 5-minute dynamic scans at tracer administration and 20- and 40-minutes post injection. Safety of 61Cu-NU101 will be evaluated by monitoring for unlikely adverse events. Ability of 61Cu-NU101to visualize malignant lesions will be evaluated by comparing the number of suspicious lesions demonstrated on the standard-of-care 18F-piflufolastat PET/CT with the number of suspicious lesions demonstrated on the experimental 61Cu-NU101PET/CT. Positive lesions will be considered to be foci greater than local background that are not physiologic/benign by location. If there is a discrepancy between the number of lesions detected by 18F-piflufolastat PET/CT and 61Cu-NU101PET/CT, then a discrepant lesion will be selected for biopsy to provide pathologic proof as a reference standard, if possible.

Determination of lesions suspicious for malignancy on 18F-piflufolastat PET/CT and 61Cu-NU101: The previously performed standard-of-care 18F-piflufolastat PET/CT and the on-trial research 61Cu-NU101will be evaluated using the same methodology, by radiologists with expertise in the interpretation of PSMA-targeted PET/CT imaging. Abnormal tracer accumulation will be defined as areas of uptake outside of sites considered physiologic or inflammatory. The locations of focal tracer abnormalities will be recorded. Radiotracer uptake will be graded on a scale of 1-5 where 1 = definitely normal, 2 = probably normal, 3 = equivocal, 4 = probably abnormal, and 5 = definitely abnormal. Semiquantitative analysis of tracer uptake will be performed for grade 4 and 5 lesions. Three-dimensional regions of interest (ROIs) will be placed in areas of tracer uptake and used for quantification of standardized uptake value (SUV), calculated as: SUV = decay-corrected mean ROI activity (μCi/ml) / (injected dose (μCi)/ body weight (g)). SUVmax will be recorded. Lesions graded as 4 (probably abnormal) or 5 (definitely abnormal) for malignancy will be counted and included in the number on lesions suspicious for malignancy in each examination.

Determination of lesions suspicious for malignancy on CT and bone scan: As a secondary objective, the number of lesions suspicious for malignancy will be compared between 61Cu-NU101and standard-of-care CT/bone scan. CT and bone scan will be interpreted by radiologists with expertise in the interpretation in CT and bone scans. Abnormal findings on CT and bone scan will be graded on a scale of 1-5 where 1 = definitely normal, 2 = probably normal, 3 = equivocal, 4 = probably abnormal, and 5 = definitely abnormal. No quantitative measurements will be made on CT and bone scan. For osseous lesions, a corresponding lesion on CT and bone scan will be counted as only 1 lesion. Lesions graded as 4 (probably abnormal) or 5 (definitely abnormal) for malignancy will be counted and included in the number on lesions suspicious for malignancy.

Interventions

• Drug Cu-NU101
  Subjects will receive a single dose of 61Cu-NU101, administered as a slow intravenous bolus over 10 seconds, with a dosage of 148 MBq (4 mCi) +/-10% , followed by PET/CT imaging 1 hour (+/- 10 minutes) and 4 hours (+/- 30 minutes) post radiotracer administration. There are no specific restrictions that should apply when administering 61Cu-NU101. There will be optional 5-minute dynamic scans at tracer administration and 20- and 40-minutes post injection.

Primary outcome measures

• Sensitivity of imaging with 61Cu- NU101, [Time frame: 4 hours post-administration]

Secondary outcome measures (1)

• Assessing the sensitivity of the 61Cu-NU101 scan [Time frame: 1 hour post-administration]

Eligibility criteria

Inclusion criteria

• Biopsy proven prostate adenocarcinoma
• Age ≥ 18 years
• ECOG 0 or 2 4 .Oligometastatic disease (1-5 radiotracer avid disease sites) on 18F- piflufolastat PET/CT within 30 days of trial recruitment

Exclusion criteria

• Known allergy/hypersensitivity to PSMA-targeted imaging agents
• Other active malignancy, other than the known prostate cancer

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Diagnostic

Study locations

United States · 2 centers

• Hoag Family Cancer Institute — Newport Beach
• Washington Univeristy School of Medicine — St Louis

Publications

• Roberts MJ, Maurer T, Perera M, Eiber M, Hope TA, Ost P, Siva S, Hofman MS, Murphy DG, Emmett L, Fendler WP. Using PSMA imaging for prognostication in localized and advanced prostate cancer. Nat Rev Urol. 2023 Jan;20(1):23-47. doi: 10.1038/s41585-022-00670-6. Epub 2022 Dec 6. PMID 36473945
• Ulaner GA, Bassett JC, Reddy R, Thomsen B, Reynolds D, Jerjian KJ, Wolfe R, Benjamin DJ, Fani M, O'Donoghue J, Baier M, Schubert N, Pais B, De Rose F, Jaafar L. 61Cu-NODAGA Prostate-specific Membrane Antigen Imaging and Therapy for Prostate Cancer: Phase 1 Trial of a New Class of 61Cu-labeled PET Radiotracers. Radiology. 2025 Dec;317(3):e251151. doi: 10.1148/radiol.251151. PMID 41363974
• van der Gaag S, Bartelink IH, Vis AN, Burchell GL, Oprea-Lager DE, Hendrikse H. Pharmacological Optimization of PSMA-Based Radioligand Therapy. Biomedicines. 2022 Nov 23;10(12):3020. doi: 10.3390/biomedicines10123020. PMID 36551776
• Chatalic KL, Heskamp S, Konijnenberg M, Molkenboer-Kuenen JD, Franssen GM, Clahsen-van Groningen MC, Schottelius M, Wester HJ, van Weerden WM, Boerman OC, de Jong M. Towards Personalized Treatment of Prostate Cancer: PSMA I&T, a Promising Prostate-Specific Membrane Antigen-Targeted Theranostic Agent. Theranostics. 2016 Apr 12;6(6):849-61. doi: 10.7150/thno.14744. eCollection 2016. PMID 27162555
• Lawhn-Heath C, Salavati A, Behr SC, Rowe SP, Calais J, Fendler WP, Eiber M, Emmett L, Hofman MS, Hope TA. Prostate-specific Membrane Antigen PET in Prostate Cancer. Radiology. 2021 May;299(2):248-260. doi: 10.1148/radiol.2021202771. Epub 2021 Mar 30. PMID 33787338
• Yilmaz U, Komek H, Can C, Altindag S. The role of (68Ga)PSMA I&T in biochemical recurrence after radical prostatectomy: detection rate and the correlation between the level of PSA, Gleason score, and the SUVmax. Ann Nucl Med. 2019 Aug;33(8):545-553. doi: 10.1007/s12149-019-01360-x. Epub 2019 May 8. PMID 31069696
• Komek H, Can C, Yilmaz U, Altindag S. Prognostic value of 68 Ga PSMA I&T PET/CT SUV parameters on survival outcome in advanced prostat cancer. Ann Nucl Med. 2018 Oct;32(8):542-552. doi: 10.1007/s12149-018-1277-5. Epub 2018 Jul 13. PMID 30006752
• Cytawa W, Seitz AK, Kircher S, Fukushima K, Tran-Gia J, Schirbel A, Bandurski T, Lass P, Krebs M, Polom W, Matuszewski M, Wester HJ, Buck AK, Kubler H, Lapa C. 68Ga-PSMA I&T PET/CT for primary staging of prostate cancer. Eur J Nucl Med Mol Imaging. 2020 Jan;47(1):168-177. doi: 10.1007/s00259-019-04524-z. Epub 2019 Sep 16. PMID 31529265

Identifiers

NCT: NCT07635524 · 149-25-CA

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗