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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT05521412




Registration number
NCT05521412
Ethics application status
Date submitted
22/08/2022
Date registered
30/08/2022
Date last updated
18/03/2024

Titles & IDs
Public title
EValuation of radIOLigand Treatment in mEn With Metastatic Castration-resistant Prostate Cancer With [161Tb]Tb-PSMA-I&T
Scientific title
EValuation of radIOLigand Treatment in mEn With Metastatic Castration-resistant Prostate Cancer With [161Tb]Tb-PSMA-I&T: Phase I/II Study
Secondary ID [1] 0 0
21/028
Universal Trial Number (UTN)
Trial acronym
VIOLET
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Prostate Cancer 0 0
Metastatic Castration-resistant Prostate Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Prostate

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - [ 161 Tb]Tb PSMA I&T

Experimental: Experimental: Treatment Arm - 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.


Treatment: Drugs: [ 161 Tb]Tb PSMA I&T
During dose escalation, doses of [161 Tb]Tb PSMA I&T will range between 4.4 GBq to 7.4 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).
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Maximum Tolerated dose (MTD)
Timepoint [1] 0 0
Dose escalation phase is expected to be completed 6 months from the time the first patient is recruited.
Primary outcome [2] 0 0
Adverse Events (AEs) and Serious Adverse Events (SAEs) measured using National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0
Timepoint [2] 0 0
Through study completion, up until 12 months after the last patient commences treatment
Primary outcome [3] 0 0
Dose Limiting toxicities (DLTs)
Timepoint [3] 0 0
Dose escalation phase is expected to be completed 6 months from the time the first patient is recruited.
Primary outcome [4] 0 0
Recommended Phase 2 Dose (RP2D)
Timepoint [4] 0 0
Up to 30 months from the time the first patient is recruited.
Secondary outcome [1] 0 0
Absorbed radiation dose
Timepoint [1] 0 0
On Day 4 of Cycle 1 (each Cycle is 42 days)
Secondary outcome [2] 0 0
50% Prostate-Specific Antigen Response Rate (PSA-RR)
Timepoint [2] 0 0
Through study completion, up until 12 months after the last patient commences treatment or until PSA progression
Secondary outcome [3] 0 0
Radiographic Progression-Free Survival (rPFS)
Timepoint [3] 0 0
Through study completion, up until 12 months after the last patient commences treatment
Secondary outcome [4] 0 0
PSA progression free survival (PSA-PFS)
Timepoint [4] 0 0
Through study completion, up until 12 months after the last patient commences treatment or until PSA progression
Secondary outcome [5] 0 0
Progression free survival (PFS)
Timepoint [5] 0 0
Through study completion, up until 12 months after the last patient commences treatment or until PSA progression
Secondary outcome [6] 0 0
Overall survival (OS)
Timepoint [6] 0 0
Through study completion, up until 12 months after the last patient commences treatment
Secondary outcome [7] 0 0
Objective response rate (ORR) by Response Evaluation Criteria in Solid Tumours version 1.1 (RECIST1.1) in patients with measurable disease
Timepoint [7] 0 0
Through study completion, up until 12 months after the last patient commences treatment
Secondary outcome [8] 0 0
Describe worst pain within 24 hours of Brief Pain Inventory-Short Form (BPI-SF) completion
Timepoint [8] 0 0
Pain will be assessed at baseline, then at 6, 12, 24, 36 and 48 weeks
Secondary outcome [9] 0 0
Health-related quality of life (HR-QoL)
Timepoint [9] 0 0
Through completion of 12 months after treatment commencement of last patient

Eligibility
Key inclusion criteria
1. Patient has provided written informed consent.

2. Male patients must be 18 years of age or older at the time of written informed
consent.

3. 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).

4. Eastern Cooperative Oncology Group (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 Response Evaluation Criteria in Solid Tumours
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 life expectancy = 6 months.

12. Patients must have adequate bone marrow, hepatic and renal function, defined as:

1. Haemoglobin = 100g/L independent of transfusions (no red blood cell transfusion
in last 4 weeks)

2. Absolute neutrophil count (ANC) = 1.5 x 10^9/L

3. Platelets = 150 x 10^9/L

4. 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

5. 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

6. Adequate renal function: patients must have a creatinine clearance estimated of =
40mL/min using the Cockcroft Gault equation (Appendix 3)

13. Sexually active patients are willing to use medically acceptable forms of barrier
contraception.

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.
Minimum age
18 Years
Maximum age
No limit
Sex
Males
Can healthy volunteers participate?
No
Key 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 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.

4. Symptomatic brain metastases or leptomeningeal metastases.

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.

Study design
Purpose of the study
Treatment
Allocation to intervention
N/A
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 1/Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
29/09/2022
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/12/2026
Actual
Sample size
Target
Accrual to date
Final
30
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
Peter MacCallum Cancer Centre - Melbourne
Recruitment postcode(s) [1] 0 0
3000 - Melbourne

Funding & Sponsors
Primary sponsor type
Other
Name
Peter MacCallum Cancer Centre, Australia
Address
Country

Ethics approval
Ethics application status

Summary
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).
Trial website
https://clinicaltrials.gov/ct2/show/NCT05521412
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries