Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12625000971437
Ethics application status
Approved
Date submitted
25/07/2025
Date registered
3/09/2025
Date last updated
3/09/2025
Date data sharing statement initially provided
3/09/2025
Type of registration
Retrospectively registered

Titles & IDs
Public title
Dose Optimisation and Prostate-Specific Membrane Antigen (PSMA) Receptor intensification with 177Lu-PSMA Therapy: A Randomised Phase II trial: OPTIMAL-PSMA
Scientific title
Dose Optimisation and PSMA Receptor intensification with 177Lu-PSMA Therapy in Patients Diagnosed with Metastatic Castrate Resistant Prostate Cancer : A Randomised Phase II trial: OPTIMAL-PSMA
Secondary ID [1] 314996 0
Nil known
Universal Trial Number (UTN)
Trial acronym
OPTIMAL-PSMA
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Metastatic Castrate Resistant Prostate Cancer (mCRPC) 338321 0
Condition category
Condition code
Cancer 334614 334614 0 0
Prostate

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Arm 1: 3 doses of [177Lu]Lu-PSMA 7.5GBq will be administered intravenously on Cycle 1 (Days 1, 3 and 15). Following this, based on the results of a week 8 PSMA-PET scan and blood PSA (ng/mL) level, a further 3 doses (10 weeks apart) will be given on Cycles 2, 3 and 4 in a biomarker guided adaptive dosing schedule. A total of 6 doses will be given.

Arm 2: 6 doses of [177Lu]Lu-PSMA 7.5GBq will be administered intravenously on a 6 weekly schedule (Cycles 1-6). A total of 6 doses will be given.

Strategies to assess adherence to the intervention include routine safety blood tests prior to each dose and in between doses, PSA levels, and scheduled imaging with SPECT/CT post doses. The exact dose activity prepared, dispensed and administered will be documented, including time, route and any residual activity, to confirm accurate dosing.
Intervention code [1] 331585 0
Treatment: Drugs
Comparator / control treatment
Arm 2 - Standard Dosing Schedule is the comparator for this study. This study is comparing the frequency that the dose of [177Lu]Lu-PSMA 7.5GBq will be administered, against the standard dosing schedule (Arm 2).

In the comparator arm, 6 doses of [177Lu]Lu-PSMA 7.5GBq will be administered intravenously on a 6 weekly schedule (Cycles 1-6). A total of 6 doses will be given.
Control group
Dose comparison

Outcomes
Primary outcome [1] 342295 0
Proportion of participants achieving a Prostate Specific Antigen (PSA) 90% response rate to therapy.
Timepoint [1] 342295 0
Bloods tests are done before every dose and in between doses to track the PSA levels and the response rate will be calculated at the end of treatment and follow-up.at 6 weeks and 12 weeks post last dose.
Secondary outcome [1] 450260 0
PSA progression free survival
Timepoint [1] 450260 0
PSA levels assessed before every dose and in between doses and in follow-up at 6 weeks and 12 weeks post last dose..
Secondary outcome [2] 450261 0
Frequency and severity of adverse events, This will be assessed as a composite outcome. Examples of very common (more than 1 in 10) possible short term side effects (within days or weeks of treatment) include nausea and injury to salivary or tear glands, leading to dry mouth or eyes. Other common possible side-effects include: vomiting, short term increased pain or pressure at the site of tumour, flu-like symptoms and reduced blood counts.
Timepoint [2] 450261 0
Adverse Events will be assessed and collected from first dose then at each patient visit until 12 weeks after end of last dose.
Secondary outcome [3] 450262 0
Overall Survival
Timepoint [3] 450262 0
From first dose, then at each patient visit until death for a maximum of 5 years post dose.
Secondary outcome [4] 450263 0
PSA 50% response rate (PSA50)
Timepoint [4] 450263 0
Baseline, prior to every dose and inbetween doses.
Secondary outcome [5] 450264 0
PSMA PET upregulation between Day 1 and Day 3 on Arm 1
Timepoint [5] 450264 0
SPECT scans are done 4 hours post every dose. Data from Day 1 and Day 3 SPECT scans will be used for this outcome.
Secondary outcome [6] 450265 0
Clinical progression free survival
Timepoint [6] 450265 0
From first dose till end of follow-up at week 12 post dose.
Secondary outcome [7] 450266 0
Circulating tumour DNA (ctDNA) evaluation with intensive initial dosing compared to standard dosing (ctDNA fraction change). This will be assessed as a composite outcome.
Timepoint [7] 450266 0
Cycle 1 Day 1, Day 3, Day 15 and Week 8 for all participants, however Day 3 and Day 15 samples are optional for participants on Arm 2.

Eligibility
Key inclusion criteria
1. Written informed consent obtained prior to the initiation of study procedures.
2. Participants aged greater than or equal to 18 years.
3. Adenocarcinoma of the prostate defined by documented histopathology of prostate adenocarcinoma or, metastatic disease typical of prostate cancer on imaging with an elevated PSA.
4. Progressive disease defined as at least one of the following:
a. PSA progression defined as 2 consecutive increases in PSA over a previous reference value measured at least 1 week prior and a minimum of 2.0 ng/mL.
b. Radiological progression on CT or Whole Body Bone Scan (WBBS) as per PCWG3 criteria or RECIST.
c. Clinical progression as determined by treating physician.
5. Evidence of metastatic disease on PSMA PET/CT and significant PSMA avidity as defined by the VISION criteria.
6. Castration-resistant disease: defined as disease progression despite castration by orchiectomy or ongoing Luteinizing Hormone-Releasing Hormone (LHRH) treatment and serum testosterone less than or equal to 1.7 nmol/L
7. Prior Androgen Receptor Pathway Inhibitor (ARPI) (e.g., abiraterone, darolutamide, apalutamide, enzalutamide) for mHSPC or mCRPC.
8. Life expectancy greater than or equal to 12 weeks
9. Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
10. Adequate organ function; documented within 28 days prior to trial registration: Haemoglobin greater than or equal to 80, Platelet count greater than or equal to 100, Neutrophils greater than 1.0
11. Willing and able to comply with all study requirements.
Minimum age
18 Years
Maximum age
No limit
Sex
Males
Can healthy volunteers participate?
No
Key exclusion criteria
1. Symptomatic or impending cord compression that has not been adequately treated and stable for greater than or equal to 4 weeks on steroid doses less than or equal to equivalent of 10mg prednisolone
2. Prior treatment with PSMA targeted radionuclide therapy.
3. Uncontrolled intercurrent illness including but not limited to; illicit drug dependency, active/recently active malignancy or psychiatric illness that could, in investigator's opinion, potentially interfere with participation in this study or places the participant at undue risk, or complicates the interpretation of safety data.
4. Inability to follow radiation safety precautions related to trial treatment.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Central randomisation by REDCap database
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation using a randomisation table created by computer software and entered into a secure ranomised module in REDCap database.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
16/06/2025
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
120
Accrual to date
15
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 28241 0
St Vincent's Hospital (Darlinghurst) - Darlinghurst
Recruitment postcode(s) [1] 44452 0
2010 - Darlinghurst

Funding & Sponsors
Funding source category [1] 319546 0
Charities/Societies/Foundations
Name [1] 319546 0
Nick Politis AM and Family Cancer Initiative Fund
Country [1] 319546 0
Australia
Funding source category [2] 319547 0
Commercial sector/Industry
Name [2] 319547 0
Telix Pharmaceuticals Limited
Country [2] 319547 0
Australia
Primary sponsor type
Hospital
Name
St Vincent's Health Network
Address
Country
Australia
Secondary sponsor category [1] 322051 0
None
Name [1] 322051 0
Address [1] 322051 0
Country [1] 322051 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 318122 0
St Vincent’s Hospital Human Research Ethics Committee
Ethics committee address [1] 318122 0
Ethics committee country [1] 318122 0
Australia
Date submitted for ethics approval [1] 318122 0
24/02/2025
Approval date [1] 318122 0
01/04/2025
Ethics approval number [1] 318122 0
2025/ETH00384

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 143186 0
Prof Louise Emmett
Address 143186 0
St Vincent's Hospital Sydney, Theranostics and Nuclear Medicine Department, Level 2, 390 Victoria Street, Darlinghurst NSW 2010
Country 143186 0
Australia
Phone 143186 0
+61 411 331 065
Fax 143186 0
Email 143186 0
[email protected]
Contact person for public queries
Name 143187 0
Louise Emmett
Address 143187 0
St Vincent's Hospital Sydney, Theranostics and Nuclear Medicine Department, Level 2, 390 Victoria Street, Darlinghurst NSW 2010
Country 143187 0
Australia
Phone 143187 0
+61 02 8382 1807
Fax 143187 0
Email 143187 0
[email protected]
Contact person for scientific queries
Name 143188 0
Louise Emmett
Address 143188 0
St Vincent's Hospital Sydney, Theranostics and Nuclear Medicine Department, Level 2, 390 Victoria Street, Darlinghurst NSW 2010
Country 143188 0
Australia
Phone 143188 0
+61 02 8382 1807
Fax 143188 0
Email 143188 0
[email protected]

Data sharing statement
Will the study consider sharing individual participant data?
No


What supporting documents are/will be available?

No Supporting Document Provided


Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.