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Trial registered on ANZCTR


Registration number
ACTRN12624000582550p
Ethics application status
Submitted, not yet approved
Date submitted
12/04/2024
Date registered
7/05/2024
Date last updated
7/05/2024
Date data sharing statement initially provided
7/05/2024
Type of registration
Prospectively registered

Titles & IDs
Public title
Evaluating the efficacy of bipolar androgen therapy in extending metastasis-free survival in patients with M0 castrate-resistant prostate cancer with prostate specific antigen progression but not radiological or clinical progression on darolutamide.
Scientific title
Evaluating the efficacy of bipolar androgen therapy in extending metastasis-free survival in patients with M0 castrate-resistant prostate cancer with prostate specific antigen progression but not radiological or clinical progression on darolutamide (WOMBAT) - ANZUP 2201
Secondary ID [1] 311949 0
Working Out M0 Bipolar Androgen Therapy (WOMBAT) - ANZUP 2201
Universal Trial Number (UTN)
Trial acronym
WOMBAT (Working Out M0 Bipolar Androgen Therapy)
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Prostate Cancer 333548 0
Condition category
Condition code
Cancer 330232 330232 0 0
Prostate

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The intervention is bipolar androgen therapy (BAT) which will be delivered in 56-day cycles. This involves an intramuscular injection of testosterone enanthate 500mg on day 1 of each 56-day cycle and darolutamide 600mg, orally, twice per day on days 29-56 of each 56-day cycle. Participants will have concomitant castration throughout via Luteinizing hormone-releasing hormone (LHRH) agonist/antagonist. The LHRH agonist/antagonist used will be as per standard of care treatment that participants were receiving prior to enrolling in the study. Participants will continue their treatment until evidence of metastatic disease on conventional imaging unless treated beyond progression. Formal drug accountability will not be performed during the study, however, will be estimated from a narrative review with each participant at appropriate clinic visits where treatment adherence will be assessed.
Intervention code [1] 328410 0
Treatment: Drugs
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 337978 0
Metastasis free survival
Timepoint [1] 337978 0
During screening and then every 8 weeks from time of commencing BAT to evidence of metastasis or death
Secondary outcome [1] 433968 0
The safety and tolerability of BAT + darolutamide
Timepoint [1] 433968 0
Continuously from time of commencing BAT until 30 days after last dose of treatment
Secondary outcome [2] 433970 0
The effect of BAT + darolutamide on Health-related Quality of Life
Timepoint [2] 433970 0
During screening and then every 2 weeks upon commencement of BAT for 8 weeks and then every 4 weeks until last dose of treatment
Secondary outcome [3] 433973 0
Prostate-specific antigen (PSA) response rate to BAT + darolutamide
Timepoint [3] 433973 0
During screening and then every 2 weeks from the time of commencing BAT for first 8 weeks and then every 4 weeks until last dose of treatment
Secondary outcome [4] 433974 0
Time to PSA progression on BAT + darolutamide
Timepoint [4] 433974 0
During screening and then every 2 weeks from the time of commencing BAT for first 8 weeks and then every 4 weeks until last dose of treatment
Secondary outcome [5] 433976 0
PSA and hormone kinetics in response to BAT + darolutamide. This will be assessed as a composite outcome.
Timepoint [5] 433976 0
Every 2 weeks for first 24 weeks from the time of commencing BAT
Secondary outcome [6] 433977 0
The effect of BAT + darolutamide on metabolic and bone turnover markers and bone mineral density. This will be assessed as a composite outcome.
Timepoint [6] 433977 0
Serum/plasma/urine - at screening and at 6 and 12 months on treatment.
Bone densitometry imaging - at screening and 12 months on treatment.

Eligibility
Key inclusion criteria
1. Histologically confirmed adenocarcinoma of the prostate
2. >=18 years of age
3. Eastern Cooperative Oncology Group (ECOG) performance status 0-1
4. PSA progression while on darolutamide defined as three rising PSA (1 baseline and 2 consecutive rises) levels at least 1 week apart despite castrate testosterone level (<1.7nmol/L).
5. PSA >2 ng/mL during screening
6. Serum testosterone <1.7nmol/L and on an LHRH agonist/antagonist
7. Adequate bone marrow function
8. Adequate liver function
9. Adequate renal function
10. Willingness and ability to comply with study requirements, including treatment and timing of treatment.
Minimum age
18 Years
Maximum age
No limit
Sex
Males
Can healthy volunteers participate?
No
Key exclusion criteria
1. Life expectancy <3 months.
2. Neuroendocrine or small cell prostate cancer on any prior diagnostic tissue sample.
3. Metastatic prostate cancer on conventional imaging (Whole body bone scan (WBBS) or CT scan). Metastatic prostate cancer evident only on Prostate Specific Membrane Antigen (PSMA) Positron Emission Tomography (PET) (without correlation on CT and bone scan or on the CT component of a PET/CT) is not an exclusion.
4. Current or prior treatment with enzalutamide, abiraterone, apalutamide, or cytotoxic chemotherapy. Ketoconazole and cyproterone are also excluded. Prior first generation Androgen receptor signalling inhibitor (ARSI) such as bicalutamide, flutamide, nilutamide are permitted.
5. Current or pre-existing cardiac or thromboembolic risk factors, including but not limited to:
i. Prior myocardial infarction, or unstable angina within 24 months of study entry,
ii. Uncontrolled or symptomatic cardiac disease including, but not limited to angina, dyspnoea on exertion, orthopnoea; cardiac failure (NYHA classification 3-4) or uncontrolled arrhythmias.
iii. Significant co-morbidities that increase cardiovascular risk, including significant hypertension (Baseline systolic BP>160 or diastolic BP>100 despite optimal treatment) that are uncontrolled, as assessed by the treating oncologist.
6. Another malignancy diagnosis within 5 years before registration. Participants with a history of treated carcinoma in situ, basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or non-muscle invasive urothelial carcinoma of the bladder are eligible. Participants with a history of other malignancies are eligible if they have been continuously disease-free for at least 5 years after definitive primary treatment or the chance of recurrence is sufficiently low as to be very unlikely to affect study outcomes according to the treating local oncologist.
7. Concurrent illness that could preclude the participant’s ability to participate in the study and follow protocol with reasonable safety.
8. Planned ongoing drug Interactions that are considered unable to be managed prior to study registration.
9. Radiation therapy within the previous 4 weeks (participants are permitted to have Stereotactic body radiotherapy (SBRT) to PSMA PET only disease prior to study enrolment if they continue on darolutamide. Note that if the metastases are visible on conventional imaging at the time of radiation treatment the participant is not eligible).

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)
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 2
Type of endpoint/s
Efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
6/09/2024
Actual
Date of last participant enrolment
Anticipated
31/08/2027
Actual
Date of last data collection
Anticipated
30/09/2027
Actual
Sample size
Target
69
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW

Funding & Sponsors
Funding source category [1] 316288 0
Commercial sector/Industry
Name [1] 316288 0
Bayer
Country [1] 316288 0
Australia
Primary sponsor type
Other Collaborative groups
Name
Australian and New Zealand Urogenital and Prostate Cancer Trials Group
Address
Country
Australia
Secondary sponsor category [1] 318477 0
None
Name [1] 318477 0
Address [1] 318477 0
Country [1] 318477 0
Other collaborator category [1] 283009 0
Other Collaborative groups
Name [1] 283009 0
The George Institute for Global Health
Address [1] 283009 0
Country [1] 283009 0
Australia

Ethics approval
Ethics application status
Submitted, not yet approved
Ethics committee name [1] 315104 0
St Vincent’s Hospital Human Research Ethics Committee
Ethics committee address [1] 315104 0
https://svhs.org.au/home/research-education/research-office
Ethics committee country [1] 315104 0
Australia
Date submitted for ethics approval [1] 315104 0
09/01/2024
Approval date [1] 315104 0
Ethics approval number [1] 315104 0

Summary
Brief summary
This is a study to assess the efficacy and safety of cyclical testosterone and darolutamide in non-metastatic castration-resistant prostate cancer.

Who is it for?
You may be eligible for this study if you are an adult male with castrate resistant prostate cancer, with no evidence of metastatic disease (M0) on conventional imaging [Whole Body Bone Scan (WBBS) and Computed Tomography (CT) scan at screening] and prostate specific antigen (PSA) only progression on darolutamide.

Study details
Study participants will receive cyclical treatment with intramuscular (IM) testosterone, darolutamide and ongoing medical/surgical castration. This will be delivered in 56-day cycles until evidence of metastatic disease on conventional imaging unless treated beyond progression. Participants will be asked to provide blood samples, complete questionnaires and undergo scans during their treatment.

It is hoped that findings from this study will help develop new treatment pathways for those with non-metastatic castration-resistant prostate cancer.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 133694 0
A/Prof Anthony Joshua
Address 133694 0
The Kinghorn Cancer Centre, Level 6, 370 Victoria Street, Darlinghurst, NSW 2010
Country 133694 0
Australia
Phone 133694 0
+61 2 9355 5655
Fax 133694 0
Email 133694 0
Anthony.Joshua@svha.org.au
Contact person for public queries
Name 133695 0
Antoinette Fontela
Address 133695 0
ANZUP Level 18, Tower 3, 300 Barangaroo Avenue, Barangaroo NSW 2000
Country 133695 0
Australia
Phone 133695 0
+61 290468954
Fax 133695 0
Email 133695 0
antoinette.fontela@anzup.org.au
Contact person for scientific queries
Name 133696 0
Anthony Joshua
Address 133696 0
The Kinghorn Cancer Centre, Level 6, 370 Victoria Street, Darlinghurst, NSW 2010
Country 133696 0
Australia
Phone 133696 0
+61 2 9355 5655
Fax 133696 0
Email 133696 0
Anthony.Joshua@svha.org.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Medical data pertaining to an individual will not be made public. Only aggregate summary data will be published.


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.