Trial Title:
Working Out M0 Bipolar Androgen Therapy
NCT ID:
NCT06594926
Condition:
Prostate Cancer
Conditions: Official terms:
Prostatic Neoplasms
Methyltestosterone
Testosterone
Testosterone undecanoate
Testosterone enanthate
Testosterone 17 beta-cypionate
Conditions: Keywords:
darolutamide
testosterone
bipolar androgen therapy
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Intervention model description:
This is a single-arm phase 2 prospective, interventional study to assess the efficacy and
safety of cyclical testosterone and darolutamide in non-metastatic castration-resistant
prostate cancer.
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Testosterone Enanthate
Description:
Testosterone enanthate is a depot formulation used in Australia typically for androgen
replacement in people with confirmed testosterone deficiency.
Arm group label:
Testosterone enthanate
Other name:
Primoteston Depot
Summary:
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)
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.
Criteria for 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).
5. PSA >2 ng/mL during screening
6. Serum testosterone <1.7nmol/L and on an LHRH agonist/antagonist
7. Adequate bone marrow function (platelets > 100 x 109/L, ANC > 1.5 x 109/L, Hb >90)
8. Adequate liver function (ALT or AST < 2.5 x ULN, bilirubin < 1.5 x ULN)
9. Adequate renal function (creatinine <1.5 x ULN) 10. 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). Metastatic
prostate cancer evident only on PSMA PET (without correlation on CT and bone scan or
on the CT component of a PET/CT) is not an exclusion.
4. Current or prior treatment with enzalutamide, abiraterone, apalutamide, or cytotoxic
chemotherapy. Ketoconazole and cyproterone are also excluded. 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 5 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. Participants with a history of other malignancies are eligible
if they have been continuously disease-free for at least 5 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).
Gender:
Male
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
St Vincents Hospital
Address:
City:
Darlinghurst
Zip:
2010
Country:
Australia
Status:
Not yet recruiting
Contact:
Last name:
Angelina Lay
Email:
angelina.lay@svha.org.au
Investigator:
Last name:
Anthony Joshua, MBBS FRACP
Email:
Principal Investigator
Investigator:
Last name:
Megan Crumbaker
Email:
Principal Investigator
Facility:
Name:
GenesisCare North Shore
Address:
City:
St Leonards
Zip:
2065
Country:
Australia
Status:
Recruiting
Contact:
Last name:
Suzi Jakicic
Email:
Suzi.Jakicic@genesiscare.com
Investigator:
Last name:
Laurence Krieger
Email:
Principal Investigator
Facility:
Name:
Sydney Adventist Hospital
Address:
City:
Wahroonga
Zip:
2076
Country:
Australia
Status:
Recruiting
Contact:
Last name:
Gloria Jeong
Phone:
029480 6285
Email:
gloria.jeong@sah.org.au
Investigator:
Last name:
Gavin Marx
Email:
Principal Investigator
Facility:
Name:
Royal Adelaide Hospital
Address:
City:
Adelaide
Zip:
5000
Country:
Australia
Status:
Recruiting
Contact:
Last name:
Sonya Stephens
Email:
sonya.stephens@sa.gov.au
Investigator:
Last name:
Thean Hsiang Tan
Email:
Principal Investigator
Start date:
August 14, 2024
Completion date:
December 31, 2028
Lead sponsor:
Agency:
Australian and New Zealand Urogenital and Prostate Cancer Trials Group
Agency class:
Other
Collaborator:
Agency:
Bayer
Agency class:
Industry
Collaborator:
Agency:
The George Institute
Agency class:
Other
Collaborator:
Agency:
HMRI
Agency class:
Other
Source:
Australian and New Zealand Urogenital and Prostate Cancer Trials Group
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06594926
