EValuation of radIOLigand Treatment in mEn With Metastatic Castration-resistant Prostate Cancer With [161Tb]Tb-PSMA-I&T

NCT05521412 | Recruiting Phase 1 DMC

• 1 other identifier: 21/028
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 1

Brief Summary

This clinical trial will evaluate the safety and efficacy of \[161Tb\]Tb -PSMA-I\&T in men with metastatic castration-resistant prostate cancer (mCRPC).

Conditions

Prostate Cancer; Metastatic Castration-resistant Prostate Cancer

Keywords

Prostate cancer; PSMA; mCRPC; PSMA-I&T; [161Tb]Tb; Terbium-161

Outcome Measures

Primary Outcomes (4)

• Maximum Tolerated dose (MTD)

  The MTD is defined as the highest dose level at which the incidence of DLT was less than 1/3 or 2/6.

  Dose escalation phase is expected to be completed 6 months from the time the first patient is recruited.

• Adverse Events (AEs) and Serious Adverse Events (SAEs) measured using National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0

  Safety of the combination will be measured by AEs and SAEs.

  Through study completion, up until 12 months after the last patient commences treatment

• Dose Limiting toxicities (DLTs)

  A DLT is defined as a toxicity that prevents further administration of the trial treatment at that dose level. Each cohort of 3 patients will be assessed for DLTs after 6 weeks from administration of cycle 1.

  Dose escalation phase is expected to be completed 6 months from the time the first patient is recruited.

• Recommended Phase 2 Dose (RP2D)

  After the MTD is established, additional patients will be treated at the MTD. Safety and efficacy data from the study will be used to define the RP2D.

  Up to 30 months from the time the first patient is recruited.

Secondary Outcomes (9)

• Absorbed radiation dose

  On Day 4 of Cycle 1 (each Cycle is 42 days)

• 50% Prostate-Specific Antigen Response Rate (PSA-RR)

  Through study completion, up until 12 months after the last patient commences treatment or until PSA progression

• Radiographic Progression-Free Survival (rPFS)

  Through study completion, up until 12 months after the last patient commences treatment

• PSA progression free survival (PSA-PFS)

  Through study completion, up until 12 months after the last patient commences treatment or until PSA progression

• Progression free survival (PFS)

  Through study completion, up until 12 months after the last patient commences treatment or until PSA progression

Study Arms (1)

Experimental: Treatment Arm

EXPERIMENTAL

In this single-arm study, patients will receive doses of \[161 Tb\]Tb PSMA I\&T on Day 1 of every 6 week Cycle. The dose of \[161 Tb\]Tb PSMA I\&T will vary in dose-escalation. Up to 6 Cycles will be given.

Drug: [ 161 Tb]Tb PSMA I&T

Interventions

[ 161 Tb]Tb PSMA I&T DRUG

During dose escalation, doses of \[161 Tb\]Tb PSMA I\&T will range between 4.4 GBq to 9.5 GBq. The recommended phase 2 dose of \[161 Tb\]Tb PSMA I\&T will be used during dose expansion. \[161Tb\]Tb-PSMA-I\&T dose will be reduced by 0.4 GBq for each subsequent cycles (2 to 6).

Experimental: Treatment Arm

Eligibility Criteria

• Age: 18 Years+
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patient has provided written informed consent.
• Male patients must be 18 years of age or older at the time of written informed consent.
• Histologically or cytologically confirmed adenocarcinoma of the prostate, OR unequivocal diagnosis of metastatic prostate cancer (i.e., involving bone or pelvic lymph nodes or para-aortic lymph nodes) with an elevated serum prostate specific antigen (PSA).
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.
• Patients must have had prior treatment with at least one line of taxane chemotherapy, unless medically unsuitable.
• Patients must have had prior treatment with at least one second-generation androgen receptor (AR)-targeted agent (e.g., enzalutamide, abiraterone, apalutamide or darolutamide).
• Patients must have progressive disease defined according to The Prostate Cancer Clinical Trials Working Group 3 (PCWG3) as any one of the following:
• PSA progression - minimum of 2 rising PSA values from a baseline measurement with an interval of ≥ 1 week between each measurement
• Soft tissue progression as per Response Evaluation Criteria in Solid Tumours version 1.1 (RECIST 1.1) criteria
• Bone progression: ≥ 2 new lesions on bone scan
• Prior surgical orchiectomy or chemical castration maintained on luteinizing hormone-releasing hormone (LHRH) analogue (agonist or antagonist).
• Serum testosterone levels ≤ 1.75nmol/L (≤ 50ng/dL).
• Significant prostate specific membrane antigen (PSMA) avidity on PSMA positron emission tomography (PET)/computed tomography (CT), defined as a minimum uptake of maximum standardised uptake value (SUVmax) 20 at a site of disease, and SUVmax \> 10 at sites of measurable soft tissue disease ≥ 15mm (unless subject to factors explaining a lower uptake, e.g. respiratory motion, reconstruction artefact).
• Patients must have a life expectancy ≥ 6 months.
• Patients must have adequate bone marrow, hepatic and renal function, defined as:

You may not qualify if:

• Prior treatment with another radioisotope (i.e. PSMA radioligands, radium-223, strontium-89, samarium-153).
• Site(s) of discordant disease on PET imaging (Fluorodeoxyglucose \[FDG\]-positive and minimal PSMA-uptake).
• Other malignancies (in addition to the prostate cancer being treated on this study) within the previous 2-years prior to registration other than basal cell or squamous cell carcinomas of skin or other cancers that are unlikely to recur within 24 months.
• Symptomatic brain metastases or leptomeningeal metastases.
• Patients with symptomatic or impending cord compression unless appropriately treated beforehand and clinically stable for more than 4 weeks.
• Concurrent illness, including severe infection that may jeopardize the ability of the patient to undergo the procedures outlined in this protocol with reasonable safety.

Sponsors & Collaborators

• Peter MacCallum Cancer Centre, Australia: lead

Study Sites (1)

Peter MacCallum Cancer Centre

Melbourne, Victoria, 3000, Australia

RECRUITING

Related Publications (1)

• Buteau JP, Kostos L, Jackson PA, Xie J, Haskali MB, Alipour R, McIntosh LE, Emmerson B, MacFarlane L, Martin CA, Chan J, Williams SE, Jewell KE, Eifer M, Hamilton AJ, Harris WQ, Akhurst T, Au L, Cardin AJ, Furic L, Kashyap RK, Kong G, Ravi Kumar AS, Murphy DG, Ravi R, Saghebi J, Sandhu S, Tran B, Azad AA, Hofman MS. First-in-human results of terbium-161 [161Tb]Tb-PSMA-I&T dual beta-Auger radioligand therapy in patients with metastatic castration-resistant prostate cancer (VIOLET): a single-centre, single-arm, phase 1/2 study. Lancet Oncol. 2025 Aug;26(8):1009-1017. doi: 10.1016/S1470-2045(25)00332-8. Epub 2025 Jul 3.

  PMID: 40617237 DERIVED

MeSH Terms

Conditions

Prostatic Neoplasms

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Central Study Contacts

James Butaeu, MD

CONTACT

(03) 855 96650; James.Buteau@petermac.org

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 22, 2022
• First Posted: August 30, 2022
• Study Start: September 29, 2022
• Primary Completion: August 3, 2025
• Study Completion (Estimated): December 1, 2026
• Last Updated: April 6, 2025

Record last verified: 2025-04

Locations

AU (1)