Testing testosterone and darolutamide for non-metastatic prostate cancer

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

This study is testing if combining testosterone with darolutamide can help men with non-metastatic prostate cancer delay the spread of their disease.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 69 (estimated)
• Ages: 18 Years and up
• Sex: Male
• Sponsor: Australian and New Zealand Urogenital and Prostate Cancer Trials Group (Academic / other)
• Drugs / interventions: chemotherapy, Radiation
• Locations: 12 sites (Garran, Australian Capital Territory and 11 other locations)
• Trial ID: NCT06594926 on ClinicalTrials.gov

What this trial studies

The WOMBAT study aims to evaluate the efficacy and safety of cyclical testosterone enanthate combined with darolutamide in patients with non-metastatic castration-resistant prostate cancer (nmCRPC). Approximately 69 participants over the age of 18 will be enrolled from various sites in Australia, all of whom will receive continuous androgen deprivation therapy alongside the study interventions. Participants will undergo treatment in 56-day cycles, with regular monitoring through blood samples, questionnaires, and imaging scans to assess disease progression. The goal is to determine if this combination therapy can delay the onset of metastatic disease.

Who should consider this trial

Good fit: Ideal candidates include adults with histologically confirmed adenocarcinoma of the prostate who have nmCRPC and are experiencing PSA progression while on darolutamide.

Not a fit: Patients with evidence of metastatic disease or those who do not meet the specific eligibility criteria will not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could provide a new treatment pathway that prolongs the time before prostate cancer spreads to other areas of the body.

How similar studies have performed: While this approach is innovative, similar studies exploring the use of testosterone in conjunction with androgen deprivation therapy have shown promise, suggesting potential for success.

Eligibility criteria

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).

Where this trial is running

Garran, Australian Capital Territory and 11 other locations

• The Canberra Hospital — Garran, Australian Capital Territory, Australia (Recruiting)
• The Border Cancer Hospital — Albury, New South Wales, Australia (Terminated)
• St Vincents Hospital — Darlinghurst, New South Wales, Australia (Recruiting)
• GenesisCare North Shore — St Leonards, New South Wales, Australia (Recruiting)
• Sydney Adventist Hospital — Wahroonga, New South Wales, Australia (Recruiting)
• ICON Cancer Centre — Chermside, Queensland, Australia (Recruiting)
• Mater Misericordiae Ltd - QLD — South Brisbane, Queensland, Australia (Recruiting)
• Royal Adelaide Hospital — Adelaide, South Australia, Australia (Recruiting)
• Grampians Health — Ballarat, Victoria, Australia (Recruiting)
• Eastern Health - Box Hill — Box Hill, Victoria, Australia (Recruiting)
• Cabrini Health — Malvern, Victoria, Australia (Recruiting)
• Northeast Health Wangaratta — Wangaratta, Victoria, Australia (Recruiting)

Study contacts

• Study coordinator: Antoinette Fontela, BSc

Conditions Prostate Cancer; darolutamide; testosterone; bipolar androgen therapy