Clinical Trial Protocol for VIOLET: A Single-Center, Phase I/II Trial Evaluation of Radioligand Treatment in Patients with Metastatic Castration-Resistant Prostate Cancer with [161Tb]Tb-PSMA-I&T
- Author(s)
- Buteau, JP; Kostos, L; Alipour, R; Jackson, P; McInstosh, L; Emmerson, B; Haskali, MB; Xie, J; Medhurst, E; Ravi, R; Gonzalez, BD; Fettke, H; Blyth, B; Furic, L; Owen, K; Sandhu, S; Murphy, DG; Azad, AA; Hofman, MS;
- Details
- Publication Year 2024-08-01,Volume 65,Issue #8,Page 1231-1238
- Journal Title
- Journal of Nuclear Medicine
- Publication Type
- Protocol
- Abstract
- [(177)Lu]Lu-PSMA is an effective class of therapy for patients with metastatic castration-resistant prostate cancer (mCRPC); however, progression is inevitable. The limited durability of response may be partially explained by the presence of micrometastatic deposits, which are energy-sheltered and receive low absorbed radiation with (177)Lu due to the approximately 0.7-mm mean pathlength. (161)Tb has abundant emission of Auger and conversion electrons that deposit a higher concentration of radiation over a shorter path, particularly to single tumor cells and micrometastases. (161)Tb has shown in vitro and in vivo efficacy superior to that of (177)Lu. We aim to demonstrate that [(161)Tb]Tb-PSMA-I&T will deliver effective radiation to sites of metastatic prostate cancer with an acceptable safety profile. Methods: This single-center, single-arm, phase I/II trial will recruit 30 patients with mCRPC. Key eligibility criteria include a diagnosis of mCRPC with progression after at least one line of taxane chemotherapy (unless medically unsuitable) and androgen receptor pathway inhibitor; prostate-specific membrane antigen-positive disease on [(68)Ga]Ga-PSMA-11 or [(18)F]DCFPyL PET/CT (SUV(max) ≥ 20); no sites of discordance on [(18)F]FDG PET/CT; adequate bone marrow, hepatic, and renal function; an Eastern Cooperative Oncology Group performance status of no more than 2, and no prior treatment with another radioisotope. The dose escalation is a 3 + 3 design to establish the safety of 3 prespecified activities of [(161)Tb]Tb-PSMA-I&T (4.4, 5.5, and 7.4 GBq). The maximum tolerated dose will be defined as the highest activity level at which a dose-limiting toxicity occurs in fewer than 2 of 6 participants. The dose expansion will include 24 participants at the maximum tolerated dose. Up to 6 cycles of [(161)Tb]Tb-PSMA-I&T will be administered intravenously every 6 wk, with each subsequent activity reduced by 0.4 GBq. The coprimary objectives are to establish the maximum tolerated dose and safety profile (Common Terminology Criteria for Adverse Events version 5.0) of [(161)Tb]Tb-PSMA-I&T. Secondary objectives include measuring absorbed radiation dose (Gy), evaluating antitumor activity (prostate-specific antigen 50% response rate, radiographic and prostate-specific antigen progression-free survival, overall survival, objective response rate), and evaluating pain (Brief Pain Inventory-Short Form) and health-related quality of life (Functional Assessment of Cancer Therapy-Prostate and Functional Assessment of Cancer Therapy-Radionuclide Therapy). Conclusion: Enrollment was completed in February 2024. Patients are still receiving [(161)Tb]Tb-PSMA-I&T.
- Publisher
- Society of Nuclear Medicine and Molecular Imaging
- Keywords
- Male; Humans; *Prostatic Neoplasms, Castration-Resistant/radiotherapy/pathology; *Neoplasm Metastasis; Ligands; Radiopharmaceuticals/therapeutic use; Aged; Middle Aged; 161Tb; Auger electrons; Psma; prostate cancer; theranostics
- Department(s)
- Cancer Imaging; Medical Oncology; Biostatistics and Clinical Trials; Laboratory Research; Surgical Oncology
- Publisher's Version
- https://doi.org/10.2967/jnumed.124.267650
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2024-08-29 01:48:27
Last Modified: 2024-08-29 01:49:12