Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12621000611820
Ethics application status
Approved
Date submitted
3/03/2021
Date registered
21/05/2021
Date last updated
8/06/2022
Date data sharing statement initially provided
21/05/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
Prostate-Specific Membrane Antigen (PSMA) Intensity Can be Altered by Androgen and phospho-SrC Obstruction
Scientific title
Prostate-Specific Membrane Antigen (PSMA) Intensity Can be Altered by Androgen and phospho-SrC Obstruction
Secondary ID [1] 303588 0
Nil Known
Universal Trial Number (UTN)
Nil Known
Trial acronym
PICAASO
Linked study record

Health condition
Health condition(s) or problem(s) studied:
metastatic castration-resistant prostate cancer 320956 0
Condition category
Condition code
Cancer 318769 318769 0 0
Prostate

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The phase 2 study will recruit men with confirmed metastatic castrate-resistant prostate cancer who have recently undergone a PSMA PET scan. Eligible participants will be assigned to either:

- Cohort A: Dasatinib 100mg once daily orally for 14 Days
- Cohort B: Dasatinib 100mg once daily and Darolumatide 600 mg twice daily orally for 14 Days

Participants can only be assigned to Cohort B once all available slots to Cohort A are filled and reviewed by investigators.

After 7 days of treatment, participants will be assessed by an investigator. After 14 (+/- 2 days) of treatment the participant will be re-imaged with a PSMA PET scan. Participants will be asked to maintain a record of drug dosing. A safety visit is scheduled at 30 days post treatment.
Intervention code [1] 319877 0
Treatment: Drugs
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 326713 0
Change in participant's tumour SUV measurements from PSMA PET scans following 2 week treatment of dasatinib alone or in combination with darolutamide
Timepoint [1] 326713 0
14 days post commencement of investigational product
Secondary outcome [1] 392455 0
To determine the safety of a 14-day course of dasatinib alone or in combination with darolutamide in men via clinical assessment by CTCAE 5.0 guidelines for adverse event(s)
Timepoint [1] 392455 0
14 days post commencement of investigational product

Eligibility
Key inclusion criteria
1. Male, aged 18 years or older
2. Pathologically confirmed adenocarcinoma of prostate or a clinical presentation consistent with prostate cancer
3. Metastatic castrate resistant prostate cancer previously confirmed on 68Ga-PSMA-11 and 18F-FDG imaging to be inadequate for future PSMA-directed theranostic treatment by a nuclear medicine physician based on FDG-discordance (FDG-positive, PSMA-negative sites of disease) OR low PSMA SUV values within 2 weeks of starting study drug
4. Adequate hematologic and organ function within 14 days before the first study treatment
5. Castrate levels of testosterone < 1.7 ng/ml
6. Provision of written informed consent.
Minimum age
18 Years
Maximum age
No limit
Sex
Males
Can healthy volunteers participate?
No
Key exclusion criteria
1. Patients who cannot lie still for at least 30 minutes or comply with imaging.
2. Previous dasatinib for prostate cancer or other condition, eg CLL
3. Allergy to dasatinib or darolutamide
4. Use of drugs that interact with interact pharmacologically with dasatinib within 1 week of study entry eg Use of CYP3A4 inducers (e.g. dexamethasone, phenytoin, carbamazepine, rifampicin, phenobarbital or St John’s Wort) and use of CYP3A4 substrates with narrow therapeutic index (e.g. astemizole, terfenadine, cisapride, pimozide, quinidine, bepridil or ergot analogues.
5. Use Concomitant use of H2 antagonists or proton pump inhibitors.
6. Current or previous (within the last 6 months) pleural effusion
7. Use of paracetamol during the study period
8. Subjects may not have any of the following: Clinical evidence of uncontrolled heart failure, myocardial infarction, or angina within the previous 6 months; prolonged QT interval Fridericia's (QTcF) > 450msec; history of unstable ventricular arrhythmias (ventricular tachycardia, ventricular fibrillation, or torsades de pointes); concomitant use of drugs known to cause torsades de pointes [quinidine, procainamide, disopyramide, amiodarone, sotalol, ibutilide, dofetilide, erythromycins, clarithromycin, chlorpromazine, haloperidol, mesoridazine,thioridazine, pimozide, cisapride, bepridil, droperidol, methadone, arsenic, chloroquine, domperidone, halofantrine, levomethadyl,pentamidine, sparfloxacin, lidoflazine] (these agents must have been discontinued at least 7 days prior to starting dasatinib)
9. Subjects may not be enrolled with any of the following: History of a significant bleeding disorder unrelated to cancer, including diagnosed congenital bleeding disorders (e.g., von Willebrand's disease), and diagnosed acquired bleeding disorder within one year (e.g., acquired anti-factor VIII antibodies); GI bleeding from any cause within 3 months

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Allocation is not concealed
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
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Efficacy
Statistical methods / analysis
The sample size of 22 patients is pragmatic rather than definitive. Based on our previous study findings(*), eleven patients will be recruited to each of two arms (dasatinib +/- Darolutamide).

Furthermore, this may allow a comparison between the arms with a 10% two-sided significance level and 80% power given a mean increase of 30% greater SUVmax mean increase with the combination with an expected SD of 20%. Additionally, descriptive statistics will be used to examine the changes in the other whole-body quantitative PET parameters (SUVmax per lesion, SUVmax, total molecular volume, SUVmean, total PSMA volume)

* Emmett, L., et al., Rapid Modulation of PSMA Expression by Androgen Deprivation: Serial (68)Ga-PSMA-11 PET in Men with Hormone-Sensitive and Castrate-Resistant Prostate Cancer Commencing Androgen Blockade. J Nucl Med, 2019. 60(7): p. 950-954.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
4/10/2021
Actual
2/11/2021
Date of last participant enrolment
Anticipated
1/02/2023
Actual
Date of last data collection
Anticipated
1/06/2023
Actual
Sample size
Target
22
Accrual to date
2
Final
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 18840 0
St Vincent's Hospital (Darlinghurst) - Darlinghurst
Recruitment hospital [2] 18841 0
Peter MacCallum Cancer Centre - Melbourne
Recruitment postcode(s) [1] 33339 0
2010 - Darlinghurst
Recruitment postcode(s) [2] 33340 0
3000 - Melbourne

Funding & Sponsors
Funding source category [1] 308009 0
Hospital
Name [1] 308009 0
St Vincent's Hospital, Sydney
Country [1] 308009 0
Australia
Funding source category [2] 308010 0
Commercial sector/Industry
Name [2] 308010 0
Bayer Australia Ltd
Country [2] 308010 0
Australia
Funding source category [3] 308011 0
Commercial sector/Industry
Name [3] 308011 0
Bristol-Myers Squibb Australia
Country [3] 308011 0
Australia
Primary sponsor type
Hospital
Name
St Vincent's Hospital, Sydney
Address
Level 6, 370 Victoria St
Darlinghurst
NSW 2010
Country
Australia
Secondary sponsor category [1] 308731 0
None
Name [1] 308731 0
None
Address [1] 308731 0
None
Country [1] 308731 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 308001 0
St Vincent's Hospital Sydney HREC
Ethics committee address [1] 308001 0
Ethics committee country [1] 308001 0
Australia
Date submitted for ethics approval [1] 308001 0
01/02/2021
Approval date [1] 308001 0
09/04/2021
Ethics approval number [1] 308001 0
2021/ETH00026

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

Contacts
Principal investigator
Name 109186 0
Prof Anthony Joshua
Address 109186 0
The Kinghorn Cancer Centre
St Vincent’s Hospital
370 Victoria St
DARLINGHURST NSW 2010
Country 109186 0
Australia
Phone 109186 0
+61 293555655
Fax 109186 0
Email 109186 0
[email protected]
Contact person for public queries
Name 109187 0
Research Manager
Address 109187 0
The Kinghorn Cancer Centre
Level 6, 370 Victoria St
DARLINGHURST NSW 2010
Country 109187 0
Australia
Phone 109187 0
+61 293555611
Fax 109187 0
61 2 9355 5735
Email 109187 0
[email protected]
Contact person for scientific queries
Name 109188 0
Anthony Joshua
Address 109188 0
The Kinghorn Cancer Centre
St Vincent’s Hospital
370 Victoria St
DARLINGHURST NSW 2010
Country 109188 0
Australia
Phone 109188 0
+61 293555655
Fax 109188 0
Email 109188 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
No individual participant data will be made available. All patient information will be de-identified as per standard SOP procedures and only presented in aggregate format to ensure patient confidentiality.


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.