Prostate CancerPhase 1/2VIOLETNCT05521412
EValuation of radIOLigand Treatment in mEn With Metastatic Castration-resistant Prostate Cancer With [161Tb]Tb-PSMA-I&T
A Phase 1/2 study testing [ 161 Tb]Tb PSMA I&T in people with Prostate Cancer and Metastatic Castration-resistant Prostate Cancer, run by Peter MacCallum Cancer Centre, Australia at 1 site in Australia.
Trial 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 more about this study
- Who is it for?
- Ages 18 years and older, men only
- Conditions the study is for
- Prostate Cancer, Metastatic Castration-resistant Prostate Cancer
- What is being tested?
- [ 161 Tb]Tb PSMA I&T
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 66 participants
- Where
- 1 siteAustralia
- Study dates
- 29 Sep 2022to Dec 2028
- Phase
- Phase 1/2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Men only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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).
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- 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:
- Haemoglobin ≥ 100g/L independent of transfusions (no red blood cell transfusion in last 4 weeks)
- Absolute neutrophil count (ANC) ≥ 1.5 x 10^9/L
- Platelets ≥ 150 x 10^9/L
- Total bilirubin ≤ 1.5x upper limit of normal (ULN) except for patients with known Gilbert's syndrome, where this applies for the unconjugated bilirubin component
- Aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 3x ULN if there is no evidence of liver metastasis or ≤ 5x ULN in the presence of liver metastases
- Adequate renal function: patients must have a creatinine clearance estimated of ≥ 40mL/min using the Cockcroft Gault equation (Appendix 3)
- Sexually active patients are willing to use medically acceptable forms of barrier contraception.
- Willing and able to comply with all study requirements, including all treatments and the timing and nature of all required assessments.
- At least 3 weeks since the completion of surgery or radiotherapy prior to registration.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Australia1 site, 1 recruiting
- Recruiting
Peter MacCallum Cancer Centre
Melbourne, Victoria, 3000
James Buteau, MD
About this study
Official title: EValuation of radIOLigand Treatment in mEn With Metastatic Castration-resistant Prostate Cancer With [161Tb]Tb-PSMA-I&T: Phase I/II Study
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.
- Being tested
- [ 161 Tb]Tb PSMA I&T
- Keywords
- Prostate cancer, PSMA, mCRPC, PSMA-I&T, [161Tb]Tb, Terbium-161
- Medical subject headings
- Prostatic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
[ 161 Tb]Tb PSMA I&TDrug
[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.
| Study group | Role | What they receive |
|---|---|---|
| Experimental: Treatment Arm | Experimental | 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. Receives: Drug: [ 161 Tb]Tb PSMA I&T |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Up to 30 months from the time the first patient is recruited.
Secondary outcomes (9)
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
Measured: On Day 4 of Cycle 1 (each Cycle is 42 days)
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.
Measured: Through study completion, up until 12 months after the last patient commences treatment or until PSA progression
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
Measured: Through study completion, up until 12 months after the last patient commences treatment
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.
Measured: Through study completion, up until 12 months after the last patient commences treatment or until PSA progression
Progression free survival (PFS)
PFS is defined as the time to PSA progression, radiographic progression, or death due to any cause
Measured: Through study completion, up until 12 months after the last patient commences treatment or until PSA progression
Overall survival (OS)
OS is defined as the time from treatment initiation to the date of death due to any cause.
Measured: Through study completion, up until 12 months after the last patient commences treatment
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.
Measured: Through study completion, up until 12 months after the last patient commences treatment
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).
Measured: Pain will be assessed at baseline, then at 6, 12, 24, 36 and 48 weeks
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
Measured: Through completion of 12 months after treatment commencement of last patient
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Aug 2022
- Study start29 Sep 2022
- Primary completionSep 2028 (estimated)
- Study completionDec 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Prostate CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 66 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Peter MacCallum Cancer Centre, Australia
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05521412
- Sponsor's protocol ID
- 21/028
- Acronym
- VIOLET
- Status last verified
- Sep 2026
- First submitted
- 22 Aug 2022
- Last updated
- 21 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
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 40617237Buteau 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