Working Out M0 Bipolar Androgen Therapy

NCT06594926 | Recruiting Phase 2 DMC

• 1 other identifier: ANZUP 2201
• Study Type: interventional
• Target: 69
• Locations: 1 country
• Sites: 12

Brief Summary

The WOMBAT study will test if BAT can prolong the time it takes for nmCRPC prostate cancer to become detectable in other areas of the body (metastatic disease). Approximately 69 participants over the age of 18 with castrate resistant prostate cancer, no evidence of metastatic disease (M0) on conventional imaging (WBBS and CT scan at screening) and PSA only progression on darolutamide will be enrolled from approximately 8 sites within Australia. Participants will receive continuous androgen deprivation therapy with LHRH agonists/antagonists. The study intervention will be IM testosterone enthanate, injected on day 1 of each 56-day cycle. Concurrent darolutamide will be taken at a dose of 600mg BD on days 29-56 of each cycle. Both LHRH and agonist/antagonist and darolutamide are supplied through the PBS as standard of care medications. Administration of both testosterone and darolutamide will continue until disease progression, beyond disease progression, unacceptable toxicity, death, withdrawal of consent or study Sponsor termination of the study. Primary objective (endpoint) is to determine the metastasis-free survival (time from commencing BAT to evidence of metastases or death)

Conditions

Prostate Cancer

Keywords

darolutamide; testosterone; bipolar androgen therapy

Outcome Measures

Primary Outcomes (1)

• Metastases free survival

  Based on PCWG3 criteria (appendix 2) and/or RECIST1.1 (appendix 1) on CT and WBBS imaging.

  From date of commencing Bipolar Androgen Therapy (BAT) until first documented evidence of metastatic disease or date of death, assessed every 8 weeks, on average 4 years

Secondary Outcomes (7)

• Safety and tolerability of BAT + darolutamide

  Continuously throughout the study, from time of commencing BAT until 30 days after last dose of treatment

• The effect of BAT + darolutamide on Health-related Quality of Life QLQ-C30

  During screening and then every 2 weeks upon commencement of BAT for 8 weeks and then every 4 weeks until last dose of treatment, on average 2 years.

• The effect of BAT + darolutamide on Health-related Quality of Life QLQ-PR25

  During screening and then every 2 weeks upon commencement of BAT for 8 weeks and then every 4 weeks until last dose of treatment, on average 2 years.

• PSA response rate to BAT + darolutamide

  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, on average 2 years

• Time to PSA progression on BAT + darolutamide

  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, on average 2 years

Study Arms (1)

Testosterone enthanate

EXPERIMENTAL

Participants will receive continuous androgen deprivation therapy with LHRH agonists/antagonists. The study intervention will be IM testosterone enthanate, injected on day 1 of each 56-day cycle (+3 days) except for cycle 1. Concurrent darolutamide will be taken at a dose of 600mg BD on days 29-56 of each cycle. Both LHRH and agonist/antagonist and darolutamide are supplied through the PBS as standard of care medications.

Drug: Testosterone Enanthate

Interventions

Testosterone Enanthate DRUG

Testosterone enanthate is a depot formulation used in Australia typically for androgen replacement in people with confirmed testosterone deficiency.

Also known as: Primoteston Depot

Testosterone enthanate

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically confirmed adenocarcinoma of the prostate
• ≥18 years of age
• ECOG performance status 0-1
• 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). Patients with a minor subsequent PSA fall, provided there was no intervening therapy since the three consecutive rises, are eligible
• AJCC stage M0 on conventional imaging.
• Previous PSMA PET only M1 disease in the hormone-sensitive setting that is now M0 CRPC on conventional imaging following \>18 months of ADT + darolutamide are eligible.
• Nodes up to 2cm in short-axis in pelvis are permitted
• PSA \>1.0 ng/mL during screening
• Serum testosterone \<1.7nmol/L and on an LHRH agonist/antagonist
• Adequate bone marrow function (platelets \> 100 x 109/L, ANC \> 1.5 x 109/L, Hb \>90)
• Adequate liver function (ALT or AST \< 2.5 x ULN, bilirubin \< 1.5 x ULN)
• Adequate renal function (creatinine \<1.5 x ULN)
• Willingness and ability to comply with study requirements, including treatment and timing of treatment.

You may not qualify if:

• Life expectancy \<3 months.
• Neuroendocrine or small cell prostate cancer on any prior diagnostic tissue sample.
• Metastatic prostate cancer on conventional imaging (WBBS or CT scan) at any point in disease course (except for pathological nodes up to 2cm in short axis in the pelvis).
• Current or prior treatment with enzalutamide, abiraterone, apalutamide, or cytotoxic chemotherapy. Patients with pelvic nodal metastases (below the aortic bifurcation) \<2cm in short axis at original diagnosis who ceased cytotoxic chemotherapy (docetaxel) at least 12 months prior to C1D1 are eligible. Prior first generation ARSI such as bicalutamide, flutamide, nilutamide are permitted.
• 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.
• 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.
• Concurrent illness that could preclude the participant's ability to participate in the study and follow protocol with reasonable safety.
• Planned ongoing drug Interactions as per protocol section 5.2.4 that are considered unable to be managed prior to study registration.
• Radiation therapy within the previous 4 weeks (participants are permitted to have 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).

Sponsors & Collaborators

• Australian and New Zealand Urogenital and Prostate Cancer Trials Group: lead
• Bayer: collaborator
• The George Institute: collaborator
• HMRI: collaborator

Study Sites (12)

The Canberra Hospital

Garran, Australian Capital Territory, 2605, Australia

RECRUITING

The Border Cancer Hospital

Albury, New South Wales, 2640, Australia

TERMINATED

St Vincents Hospital

Darlinghurst, New South Wales, 2010, Australia

RECRUITING

GenesisCare North Shore

St Leonards, New South Wales, 2065, Australia

RECRUITING

Sydney Adventist Hospital

Wahroonga, New South Wales, 2076, Australia

RECRUITING

ICON Cancer Centre

Chermside, Queensland, 4032, Australia

RECRUITING

Mater Misericordiae Ltd - QLD

South Brisbane, Queensland, 4101, Australia

RECRUITING

Royal Adelaide Hospital

Adelaide, South Australia, 5000, Australia

RECRUITING

Grampians Health

Ballarat, Victoria, 3350, Australia

RECRUITING

Eastern Health - Box Hill

Box Hill, Victoria, 3128, Australia

RECRUITING

Cabrini Health

Malvern, Victoria, 3144, Australia

RECRUITING

Northeast Health Wangaratta

Wangaratta, Victoria, 3677, Australia

RECRUITING

Related Publications (1)

• Talmor B, Harris CA, Gianacas C, Pook D, Tan TH, Davis ID, Krieger L, Marx G, Anton A, Sharma S, Goh JC, Xu K, Pranavan G, Dhillon HM, Antonarakis ES, Denmeade SR, Horvath L, Oakes SR, Allen R, Fontela A, Reich E, Crumbaker M, Hurwitz J, Joshua AM. WOMBAT (ANZUP 2201): A Phase 2, Single-arm Study of Bipolar Androgen Therapy in Patients with Nonmetastatic Castration-resistant Prostate Cancer with Prostate-specific Antigen Progression on Darolutamide. Eur Urol Oncol. 2026 Feb 21:S2588-9311(26)00041-6. doi: 10.1016/j.euo.2026.02.004. Online ahead of print.

  PMID: 41724634 DERIVED

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

testosterone enanthate

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Study Officials

• Anthony Joshua

  St Vincent's Hospital, Sydney

  STUDY CHAIR

Central Study Contacts

Antoinette Fontela, BSc

CONTACT

+61 2 9046 8954; Trials@anzup.org.au

Jennifer Thompson, BSc

CONTACT

jennifer.thompson@anzup.org.au

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This is a single-arm phase 2 prospective, interventional study to assess the efficacy and safety of cyclical testosterone and darolutamide in non-metastatic castration-resistant prostate cancer.

Study Record Dates

• First Submitted: May 23, 2024
• First Posted: September 19, 2024
• Study Start: August 14, 2024
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2028
• Last Updated: April 24, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

AU (12)