Working Out M0 Bipolar Androgen Therapy

Launched by AUSTRALIAN AND NEW ZEALAND UROGENITAL AND PROSTATE CANCER TRIALS GROUP · Sep 10, 2024

Keywords

ClinConnect Summary

The WOMBAT study is a clinical trial aimed at exploring whether a specific type of therapy, known as Bipolar Androgen Therapy (BAT), can help delay the spread of prostate cancer that is resistant to standard hormone therapy and has not yet spread to other parts of the body. This study will involve about 69 men aged 18 and older who have been diagnosed with castrate-resistant prostate cancer but do not show any signs of the disease spreading on standard imaging tests. Eligible participants must have rising prostate-specific antigen (PSA) levels while on a medication called darolutamide. They will receive a combination of hormone treatments, including an injection of testosterone and the oral medication darolutamide, over a series of 56-day cycles until the cancer progresses or they decide to withdraw from the study.

Men interested in participating should know that they will need to meet certain criteria, such as having a confirmed diagnosis of prostate cancer and adequate organ function. They should also not have any serious heart conditions or other significant health issues that could interfere with their participation. Throughout the study, participants will be closely monitored for any side effects or changes in their condition, and they will play a crucial role in helping researchers understand how effective this new treatment approach can be in managing prostate cancer.

Gender

MALE

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).