ClinicalTrials.gg
RecruitingNCT05521412VIOLETUpdated Sep 21, 2026

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

A Phase 1/2 interventional study of [ 161 Tb]Tb PSMA I&T in Prostate Cancer and Metastatic Castration-resistant Prostate Cancer, sponsored by Peter MacCallum Cancer Centre, Australia. Recruiting at 1 site in Australia. Open to male participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-09-21.

Sponsored by Peter MacCallum Cancer Centre, Australia · Phase 1/2, Interventional, and Treatment

From the registry’s dates

  • Started Sep 2022; still recruiting 4 years 1 month later.
Phase
Phase 1/2
Study type
Interventional
Enrollment
66
Allocation
Not applicable
Ages
18 Years and older
Sex
Male
01

Study 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).

Read the detailed description

This prospective, single-centre, single-arm phase I/II trial will assess the safety, efficacy and anti-tumour activity of [161Tb]Tb-PSMA-I\&T in patients with mCRPC.

This study aims to assess and establish the maximum tolerated dose (MTD), dose-limiting toxicities (DLTs) and recommended phase 2 dose (RP2D) of [161Tb]Tb-PSMA-I\&T in patients with mCRPC.

66 men with mCRPC who have progressed with at least one line of taxane chemotherapy and at least one second-generation androgen receptor (AR)-targeted agent will be enrolled in this trial in two stages: dose escalation and a dose expansion phase.

02

Conditions studied

  • Prostate Cancer
  • Metastatic Castration-resistant Prostate Cancer

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Keywords

  • Prostate cancer
  • PSMA
  • mCRPC
  • PSMA-I&T
  • [161Tb]Tb
  • Terbium-161
03

In context

Prostatic Neoplasms

7,046 studies on the registry are indexed under Prostatic Neoplasms; 1,580 are open to participants now.

This study's planned enrollment of 66 is close to the median of 60 across 5,348 interventional studies indexed under Prostatic Neoplasms.

Browse Prostatic Neoplasms studies →

Lead sponsor

Peter MacCallum Cancer Centre, Australia is the lead sponsor of 82 studies on the registry; 25 are open to participants now.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
Male
Accepts healthy volunteers
No

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

Inclusion criteria

  1. Patient has provided written .
  2. Male patients must be 18 years of age or older at the time of written informed consent.
  3. or cytologically confirmed adenocarcinoma of the prostate, OR unequivocal diagnosis of prostate cancer (i.e., involving bone or pelvic lymph nodes or para-aortic lymph nodes) with an elevated serum prostate specific antigen (PSA).
  4. (ECOG) performance status ≤ 2.
  5. Patients must have had prior treatment with at least one line of taxane chemotherapy, unless medically unsuitable.
  6. Patients must have had prior treatment with at least one second-generation androgen receptor (AR)-targeted agent (e.g., enzalutamide, abiraterone, apalutamide or darolutamide).
  7. Patients must have progressive disease defined according to The Prostate Cancer Clinical Trials Working Group 3 (PCWG3) as any one of the following:

    1. PSA progression - minimum of 2 rising PSA values from a baseline measurement with an interval of ≥ 1 week between each measurement
    2. Soft tissue progression as per version 1.1 (RECIST 1.1) criteria
    3. Bone progression: ≥ 2 new lesions on bone scan
  8. Prior surgical orchiectomy or chemical castration maintained on luteinizing hormone-releasing hormone (LHRH) analogue (agonist or antagonist).
  9. Serum testosterone levels ≤ 1.75nmol/L (≤ 50ng/dL).
  10. 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).
  11. Patients must have a ≥ 6 months.
  12. Patients must have adequate bone marrow, hepatic and renal function, defined as:

    1. ≥ 100g/L independent of transfusions (no red blood cell transfusion in last 4 weeks)
    2. (ANC) ≥ 1.5 x 10\^9/L
    3. ≥ 150 x 10\^9/L
    4. Total ≤ 1.5x (ULN) except for patients with known Gilbert's syndrome, where this applies for the unconjugated bilirubin component
    5. (AST) and alanine transaminase (ALT) ≤ 3x ULN if there is no evidence of liver metastasis or ≤ 5x ULN in the presence of liver metastases
    6. Adequate renal function: patients must have a estimated of ≥ 40mL/min using the Cockcroft Gault equation (Appendix 3)
  13. Sexually active patients are willing to use medically acceptable forms of barrier .
  14. Willing and able to comply with all study requirements, including all treatments and the timing and nature of all required assessments.
  15. At least 3 weeks since the completion of surgery or radiotherapy prior to registration.

Exclusion criteria

Exclusion Criteria:

  1. Prior treatment with another radioisotope (i.e. PSMA radioligands, radium-223, strontium-89, samarium-153).
  2. Site(s) of discordant disease on PET imaging (Fluorodeoxyglucose [FDG]-positive and minimal PSMA-uptake).
  3. Other (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.
  4. Symptomatic or .
  5. Patients with symptomatic or impending cord compression unless appropriately treated beforehand and clinically stable for more than 4 weeks.
  6. Concurrent illness, including severe infection that may jeopardize the ability of the patient to undergo the procedures outlined in this protocol with reasonable safety.
Terms in these criteria, in plain language(17)

Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.

Informed consent

Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.

You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.

Histologically or cytologically confirmed

The diagnosis was confirmed by looking at a sample under a microscope: tissue from a biopsy or surgery (histology), or cells from a fluid or needle sample (cytology).

Your pathology report is the document that shows this.

Metastases

Cancer that has spread from where it began to other parts of the body. “Metastatic” cancer is cancer that has spread this way.

ECOG performance status

A scale of how much an illness limits everyday activity. For people being assessed to join a study, scores run from 0 (fully active) to 4; lower is more active.

0
Fully active, no restrictions.
1
Limited in strenuous activity, but walking and able to do light work, such as housework or office work.
2
Walking and able to look after yourself, but unable to work; up and about more than half of waking hours.
3
Able to look after yourself only in part; in bed or a chair more than half of waking hours.
4
Unable to look after yourself at all; in bed or a chair all day.

Studies most often ask for 0–1 or 0–2. Your doctor gives the score; the WHO scale uses the same steps. The full scale also has 5, which records death.

RECIST

The standard rules for measuring tumours on CT or MRI scans, to tell whether a cancer is shrinking, stable or growing during treatment.

“Measurable disease per RECIST 1.1” usually means at least one tumour 10 mm or more at its longest on a CT scan, or a lymph node 15 mm or more across its short axis.

Life expectancy

The study doctor’s estimate of how long someone is likely to live. Criteria use it so that people can stay in the study long enough for it to answer its question.

Hemoglobin (Hb)

The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).

Absolute neutrophil count (ANC)

The number of neutrophils, white blood cells that help fight infection, in a given amount of blood. Too few raises the risk of infection.

It is a count, not a percentage of the white cells. Limits are written in units that mean the same: ≥ 1.5 × 10⁹/L is ≥ 1,500 per mm³ (µL). Each lab has its own reference range.

Platelets

Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.

Bilirubin

A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.

Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.

ULN (upper limit of normal)

The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.

“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.

ALT and AST (liver enzymes)

Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.

Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.

Creatinine clearance (CrCl)

How quickly the kidneys clear creatinine, a waste product, from the blood. A study may estimate it from a blood test with age, weight and sex (often by the Cockcroft–Gault formula), or measure it using blood and urine collected over a set time. Given in mL/min; higher is better.

Contraception

Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.

Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.

Cancer (malignancy)

Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.

Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.

Brain metastases

Cancer deposits in the brain from a cancer that started elsewhere in the body (CNS metastases include the spinal cord).

Studies differ: some leave out any brain metastases, some accept ones treated and stable for some weeks. Check what this study allows.

Leptomeningeal disease

Cancer that has spread to the leptomeninges, the thin layers covering the brain and spinal cord, and the fluid between them. It is not the same as brain metastases.

Criteria often treat it separately, and many studies leave it out even where treated brain metastases are allowed.

05

Study design

Phase
Phase 1 / Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
66 participants (estimated)

Study arms

  • Experimental
    Experimental: Treatment Arm

    Experimental: Cohort A: 30 patients will patients will receive \[161Tb\]Tb PSMA I\&T on Day 1 of every 6 week Cycle. The administered activity for cycle 1 of will vary in dose-escalation ranging from 4.4 GBq to 7.4 GBq, using a 3+3 design. Cohort B: 12 patients will receive \[161Tb\]Tb PSMA I\&T on Day 1 of every 6 week Cycle. The administered activity for cycle 1 will be 9.5 GBq. Cohort C: 24 patients will receive a modified schedule of treatment. \[161Tb\]Tb -PSMA-I\&T will be administered at Weeks 0, 2, 6, 12, 20, and 30 (Week 0 = Cycle 1 Day 1). In Cycle 1, administration occurs on Days 1 and 15. In Cycles 2-5, dosing occurs once on Day 1 of each cycle, with cycle durations of 6, 6, 8, 10, and 6 weeks. The administered activity for cycle 1 will be 9.5 GBq.

    Drug: [ 161 Tb]Tb PSMA I&T

Interventions

  • Drug[ 161 Tb]Tb PSMA I&T

    \[161Tb\]Tb PSMA I\&T commencing as specified for cycle 1, with administered activity reduced by 0.4 GBq for each cycle (2 to 6). The first 3 patients of each dose level or modified schedule of treatment will be subject to safety review prior to dose expansion phase.

06

What researchers measure

Primary outcomes

  1. 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.

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

  2. 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.

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

  3. 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.

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

  4. 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.

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

Secondary outcomes

  1. Absorbed radiation dose

    Absorbed radiation dose will be determined using the SPECT/CT imaging after administration of the first dose of \[161Tb\]Tb-PSMA-I\&T

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

  2. 50% Prostate-Specific Antigen Response Rate (PSA-RR)

    PSA will be assessed at baseline and every 3 weeks from Cycle 1 Day 1 during treatment, and every 6 weeks during follow-up. PSA response will be defined as a 50% or greater decrease in PSA from baseline to the lowest post-baseline PSA result.

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

  3. Radiographic Progression-Free Survival (rPFS)

    rPFS is defined as the time from registration to the first date of documented radiographic progression using conventional imaging or death due to any cause, whichever occurs first. Radiographic progression will be assessed by the Investigator per RECIST 1.1 for soft tissue and PCWG3 for bone lesions

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

  4. PSA progression free survival (PSA-PFS)

    PSA progression is defined as a rise in PSA by more than 25% AND more than 2ng/mL above the nadir (lowest PSA point). This needs to be confirmed by a repeat PSA performed at least 3 weeks later. Early rises in PSA prior to 12 weeks will be disregarded in determining PSA progression.

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

  5. Progression free survival (PFS)

    PFS is defined as the time to PSA progression, radiographic progression, or death due to any cause

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

  6. Overall survival (OS)

    OS is defined as the time from treatment initiation to the date of death due to any cause.

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

  7. Objective response rate (ORR) by Response Evaluation Criteria in Solid Tumours version 1.1 (RECIST1.1) in patients with measurable disease

    Objective Response (OR) is only applicable for the subset of patients with measurable disease by RECIST1.1. OR is defined as a partial response (PR) or complete response (CR) at any stage from time of commencement of protocol treatment to the time of subsequent systemic anti-cancer treatment. The ORR is calculated as the proportion of patients with a best response of CR or PR.

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

  8. Describe worst pain within 24 hours of Brief Pain Inventory-Short Form (BPI-SF) completion

    Pain will be assessed using the Brief Pain Inventory-Short Form (BPI-SF).

    Time frame: Pain will be assessed at baseline, then at 6, 12, 24, 36 and 48 weeks

  9. Health-related quality of life (HR-QoL)

    HR-QoL will be assessed using the Functional Assessment of Cancer Therapy-Prostate (FACT-P) questionnaire. The endpoint is the trial outcome index (TOI) score from FACT-P

    Time frame: Through completion of 12 months after treatment commencement of last patient

07

Study locations

1 of 1 sites recruiting
08

References and documents

Publications

  • 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. PubMed 40617237 ↗
  • 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. 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. J Nucl Med. 2024 Aug 1;65(8):1231-1238. doi: 10.2967/jnumed.124.267650. PubMed 38991752 ↗
09

Timeline

Tracking since Sep 25, 2026
ElapsedEstimatedEstimated, not yet reachedSimilar studies: half by the dot; the band is the middle halfHalf of similar studies reached it by the dot; the band is the middle half, from a quarter to three quarters

Started Sep 2022 (actual). Primary completion is estimated for Sep 2028, 72 months after the start.

Of 114 non-industry phase 1/2 interventional studies under Prostatic Neoplasms, half reached primary completion within 65 months of starting (the median), counting those still running; a quarter within 28 and three quarters within 85. This study's planned 72 months is above that.

Counting every sponsor, half of 210 studies reached it within 61 months; a quarter within 30 and three quarters within 85.

How these figures are worked out, and which studies are left out of them.

Registered
Aug 22, 2022
First posted
Aug 30, 2022
StartActual
Sep 29, 2022
Primary completionEst.
Sep 2028
CompletionEst.
Dec 2028
Last update
Sep 21, 2026
What these dates mean
Start.
When the first participant enrolled; while estimated, when the study expects to open to recruitment.
Primary completion.
When the last participant was examined or treated to collect data for the study's main question, its primary outcome. A study that stopped early gives the date its data collection stopped.
Completion.
When the last participant's last visit took place, for every outcome, secondary ones and side effects included: the end of the study. Often later than primary completion, sometimes the same day.
Actual and Est.
Actual means the registry says the date has happened. Est. (estimated) is a date the sponsor plans or expects. It can still move, and the sponsor is expected to change it to actual once it has passed.
No changes since tracking began. The registry record was last updated on Sep 21, 2026, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
10

Registry details

Key details

Study ID
NCT05521412
Lead sponsor
Peter MacCallum Cancer Centre, Australia
Responsible party
Sponsor
First posted
Aug 30, 2022
Start date
Sep 29, 2022
Primary completion
Sep 2028 (estimated)
Completion
Dec 2028 (estimated)
Last update
Sep 21, 2026

Study contacts

James Butaeu, MD
Contact
James.Buteau@petermac.org
(03) 855 96650

Oversight

Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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