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)
• 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.