Working Out M0 Bipolar Androgen Therapy

About This Trial

This study is testing whether alternating between high doses of testosterone and a standard prostate cancer drug can help delay the cancer from spreading to other parts of the body.
It is for adults whose prostate cancer has not spread on regular scans, but whose PSA levels are rising while taking the medication darolutamide.
Participants will stay on their regular hormone-lowering therapy, receive a testosterone injection once every eight weeks, and take darolutamide pills for part of each cycle.
Before considering this trial, you should know that people with a history of serious heart problems or those who have previously received chemotherapy or certain other advanced hormone drugs are not eligible.

More Information

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)

Who Can Enroll

Age Range: 18 years and older
Gender: Male
Who This Trial is For: This study is testing whether alternating between high doses of testosterone and a standard prostate cancer drug can help delay the cancer from spreading to other parts of the body.

Study Details

Start Date: August 14, 2024
Lead Sponsor: Australian and New Zealand Urogenital and Prostate Cancer Trials Group

Full Eligibility Criteria

Inclusion Criteria

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 (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 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.

Exclusion Criteria

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) 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).