Trial Review

The ANZCTR website will be unavailable from 1-2pm (AEST) on Thursday 22nd May for website maintenance. Please be sure to log out of the system in order to avoid any loss of data.

Reset your password and enable multi-factor authentication (MFA)


For ANZCTR account holders: to help ensure the cyber safety of your account, you’ll need to reset your password and set-up multi-factor authentication (MFA) as per the instructions below.


  1. Go to the Login page, click ‘reset password’ and follow the instructions.
  2. Check your email for the link to set a new password.
  3. Create a new password that meets requirements. New passwords must include at least one lowercase letter, one uppercase letter, one number and one special character (e.g. !#$%&@).
  4. Return to the Login page and enter your new password. A verification code will be sent to your email.
  5. Check your email for the code and enter it on the Login page. If the code is entered incorrectly, you can re-enter the correct one or request a new one.

Learn more about MFA and its importance on the Australian Signals Directorate website.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial registered on ANZCTR


Registration number
ACTRN12624000582550
Ethics application status
Approved
Date submitted
12/04/2024
Date registered
7/05/2024
Date last updated
27/04/2025
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
Assessment method [1] 337978 0
Assessed by site investigators using (computed tomography) CT scans and (Response evaluation criteria in solid tumors) RECIST v1.1 criteria or PCWG3 criteria.
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
Assessment method [1] 433968 0
Incidence and grade of adverse events (AE) by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) criteria v.5.0
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
Assessment method [2] 433970 0
Using the European Organisation for Research Treatment of Cancer (EORTC) quality of life questionnaires QLQ-C30 and QLQ-PR25. This will be assessed as a composite outcome.
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
Assessment method [3] 433973 0
By testing PSA level in blood. PSA response rate is defined as a PSA reduction of >=50% from baseline as per PCWG3 criteria
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
Assessment method [4] 433974 0
By testing PSA level in blood. PSA progression is defined as a PSA increase of >=25% from baseline or nadir, confirmed on subsequent test >=1 week later as per PCWG3)
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.
Assessment method [5] 433976 0
Blood tests assessing change in PSA, testosterone, oestradiol, Dihydrotestosterone (DHT), Dehydroepiandrosterone (DHEA), sex hormone-binding globulin (SBHG)
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.
Assessment method [6] 433977 0
Testing bone turnover markers via serum procollagen type I N propeptide (PINP) and plasma C-terminal cross-linking telopeptide of type I collagen (CTX). Bone densitometry imaging.
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 (18 months of ADT + darolutamide are eligible.
b. Nodes up to 2cm in short-axis in pelvis are permitted
6. PSA >1.0 ng/mL during screening
7. Serum testosterone <1.7nmol/L and on an LHRH agonist/antagonist
8. Adequate bone marrow function
9. Adequate liver function
10. Adequate renal function
11. 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 160 or diastolic BP>100 despite optimal treatment) that are uncontrolled, as assessed by the treating oncologist.
6. Another malignancy diagnosis within 2 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 if malignancy has been treated with curative intent. Participants with a history of other malignancies are eligible if they have been continuously disease-free for at least 2 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
Recruiting
Date of first participant enrolment
Anticipated
1/11/2024
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
0
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 27276 0
Sydney Adventist Hospital - Wahroonga
Recruitment hospital [2] 27277 0
The Royal Adelaide Hospital - Adelaide
Recruitment hospital [3] 27278 0
GenesisCare – North Shore - St Leonards
Recruitment hospital [4] 27477 0
Cabrini Hospital - Malvern - Malvern
Recruitment hospital [5] 27478 0
Icon Cancer Care Chermside - Chermside
Recruitment hospital [6] 27479 0
Ballarat Health Services (Base Hospital) - Ballarat Central
Recruitment hospital [7] 27837 0
The Border Cancer Hospital - Albury
Recruitment hospital [8] 27838 0
St Vincent's Hospital (Darlinghurst) - Darlinghurst
Recruitment hospital [9] 27839 0
Eastern Health - Box Hill
Recruitment postcode(s) [1] 43363 0
2076 - Wahroonga
Recruitment postcode(s) [2] 43364 0
5000 - Adelaide
Recruitment postcode(s) [3] 43365 0
2065 - St Leonards
Recruitment postcode(s) [4] 43586 0
3144 - Malvern
Recruitment postcode(s) [5] 43587 0
4032 - Chermside
Recruitment postcode(s) [6] 43588 0
3350 - Ballarat Central
Recruitment postcode(s) [7] 44032 0
2640 - Albury
Recruitment postcode(s) [8] 44033 0
2010 - Darlinghurst
Recruitment postcode(s) [9] 44034 0
3128 - Box Hill

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
Country
Australia
Secondary sponsor category [1] 318477 0
None
Name [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
Country [1] 283009 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 315104 0
St Vincent’s Hospital Human Research Ethics Committee
Ethics committee address [1] 315104 0
Ethics committee country [1] 315104 0
Australia
Date submitted for ethics approval [1] 315104 0
09/01/2024
Approval date [1] 315104 0
16/05/2024
Ethics approval number [1] 315104 0
2024/ETH00057

Summary
Brief summary
Trial website
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
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
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
Email 133696 0
Anthony.Joshua@svha.org.au

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