Working Out M0 Bipolar Androgen Therapy (WOMBAT)

April 22, 2026 updated by: Australian and New Zealand Urogenital and Prostate Cancer Trials Group

Evaluating the Efficacy of Bipolar Androgen Therapy in Extending Metastasis-free Survival in Patients With M0 Castrate-resistant Prostate Cancer With PSA Progression But Not Radiological or Clinical Progression on Darolutamide

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)

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

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

Adults 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 may be eligible.

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.

Study Type

Interventional

Enrollment (Estimated)

69

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Australia
    • Australian Capital Territory
      • Garran, Australian Capital Territory, Australia, 2605
    • New South Wales
      • Albury, New South Wales, Australia, 2640
        • Terminated
        • The Border Cancer Hospital
      • Darlinghurst, New South Wales, Australia, 2010
        • Recruiting
        • St Vincents Hospital
        • Principal Investigator:
          • Anthony Joshua, MBBS FRACP
        • Principal Investigator:
          • Megan Crumbaker
        • Contact:
      • St Leonards, New South Wales, Australia, 2065
      • Wahroonga, New South Wales, Australia, 2076
        • Recruiting
        • Sydney Adventist Hospital
        • Principal Investigator:
          • Gavin Marx
        • Contact:
    • Queensland
      • Chermside, Queensland, Australia, 4032
        • Recruiting
        • Icon Cancer Centre
        • Principal Investigator:
          • Jeffrey Goh
        • Contact:
      • South Brisbane, Queensland, Australia, 4101
    • South Australia
      • Adelaide, South Australia, Australia, 5000
        • Recruiting
        • Royal Adelaide Hospital
        • Principal Investigator:
          • Thean Hsiang Tan
        • Contact:
    • Victoria
      • Ballarat, Victoria, Australia, 3350
        • Recruiting
        • Grampians Health
        • Contact:
        • Principal Investigator:
          • Sharad Sharma
      • Box Hill, Victoria, Australia, 3128
        • Recruiting
        • Eastern Health - Box Hill
        • Contact:
        • Contact:
        • Principal Investigator:
          • Arsha Anton
      • Malvern, Victoria, Australia, 3144
        • Recruiting
        • Cabrini Health
        • Principal Investigator:
          • David Pook
        • Contact:
      • Wangaratta, Victoria, Australia, 3677
        • Recruiting
        • Northeast Health Wangaratta
        • Contact:
        • Principal Investigator:
          • Kay Xu

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Histologically confirmed adenocarcinoma of the prostate
  2. ≥18 years of age
  3. 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). Patients with a minor subsequent PSA fall, provided there was no intervening therapy since the three consecutive rises, are eligible

  5. AJCC stage M0 on conventional imaging.

    1. 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.
    2. 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 (platelets > 100 x 109/L, ANC > 1.5 x 109/L, Hb >90)
  9. Adequate liver function (ALT or AST < 2.5 x ULN, bilirubin < 1.5 x ULN)
  10. Adequate renal function (creatinine <1.5 x ULN)
  11. Willingness and ability to comply with study requirements, including treatment and timing of treatment.

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 (WBBS or CT scan) at any point in disease course (except for pathological nodes up to 2cm in short axis in the pelvis).
  4. 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.

  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 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 as per protocol section 5.2.4 that are considered unable to be managed prior to study registration.
  9. 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).

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Testosterone enthanate
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
Testosterone enanthate is a depot formulation used in Australia typically for androgen replacement in people with confirmed testosterone deficiency.
Other Names:
  • Primoteston Depot

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Metastases free survival
Time Frame: 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
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Safety and tolerability of BAT + darolutamide
Time Frame: Continuously throughout the study, from time of commencing BAT until 30 days after last dose of treatment
The safety and tolerability of BAT + darolutamide (Incidence and grade of AEs by NCI CTCAE v5.0 Common Terminology Criteria for Adverse Events will be used to grade and classify adverse events after each cycle. Adverse events will be reported as all grade, grade 3-4, grade 5 and Adverse events of special interest (related to bipolar androgen therapy).
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
Time Frame: 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.
Using the European Organisation for Research Treatment of Cancer (EORTC) quality of life (QOL) questionnaire QLQ-C30. QLQ-C30 uses 28 questions about overall QOL with each question answerable using a scale from 1 (not at all) to 4 (very much). Overall scores can be from a minimum of 28 indicating a better QOL and higher scores with a maximum of 112 indicating lower overall QOL. It has two summary questions which asks participants to rank, 1) overall health and 2) overall QOL on scale from 1: very poor, to 7; excellent.
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
Time Frame: 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.
Using the European Organisation for Research Treatment of Cancer (EORTC) quality of life (QOL) questionnaire QLQ-PR25. QLQ-PR25 is a supplement to QLQ-C30 and designed to assess symptoms related to prostate cancer, treatment, and aspects of life related to prostate cancer.QLQ-PR25 uses 25 questions about overall QOL with each question answerable using a scale from 1 (not at all) to 4 (very much). Overall scores can be from a minimum of 25 indicating a better QOL and higher scores with a maximum of 100 indicating lower overall QOL.
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
Time Frame: 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
By testing PSA level in blood. PSA response rate is defined as a PSA reduction of >=50% from baseline as per PCWG3 criteria
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
Time Frame: 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
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)
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
PSA and hormone kinetics in response to BAT + darolutamide. This will be assessed as a composite outcome.
Time Frame: Every 2 weeks for first 24 weeks from the time of commencing BAT
Blood tests assessing change in PSA, testosterone, oestradiol, Dihydrotestosterone (DHT), Dehydroepiandrosterone (DHEA), sex hormone-binding globulin (SBHG)
Every 2 weeks for first 24 weeks from the time of commencing BAT
The effect of BAT + darolutamide on metabolic and bone turnover markers and bone mineral density. This will be assessed as a composite outcome.
Time Frame: Serum/plasma/urine - at screening and at 6 and 12 months on treatment. Bone densitometry imaging - at screening and 12 months on treatment.
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.
Serum/plasma/urine - at screening and at 6 and 12 months on treatment. Bone densitometry imaging - at screening and 12 months on treatment.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Australian and New Zealand Urogenital and Prostate Cancer Trials Group

Collaborators

Bayer
The George Institute
HMRI

Investigators

  • Study Chair: Anthony Joshua, St Vincent's Hospital, Sydney

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

August 14, 2024

Primary Completion (Estimated)

December 31, 2026

Study Completion (Estimated)

December 31, 2028

Study Registration Dates

First Submitted

May 23, 2024

First Submitted That Met QC Criteria

September 10, 2024

First Posted (Actual)

September 19, 2024

Study Record Updates

Last Update Posted (Actual)

April 24, 2026

Last Update Submitted That Met QC Criteria

April 22, 2026

Last Verified

April 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ANZUP 2201

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Prostate Cancer

Clinical Trials on Testosterone Enanthate

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Switzerland

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe