Efficacy of Darolutamide and Bipolar Androgen Therapy in Metastatic Castration-Resistant Prostate Cancer: A Randomized Controlled Trial
- Trial ID
- 2025-521051-23-00
- Protocol
- UniMS22_0022
- Sponsor
- Universitaet Muenster
Trial statistics
Diseases & Conditions
Objectives
The primary objective of the DaroBAT trial is to evaluate the **efficacy** of bipolar androgen therapy (BAT) and **Darolutamide** in combination with androgen deprivation therapy (ADT) compared to the standard of care (SOC) with ADT in patients with **metastatic castration-resistant prostate cancer** (mCRPC). This is assessed by measuring **progression-free survival** (PFS) and **quality of life**. The clinical relevance of this objective lies in potentially improving treatment outcomes and quality of life for patients with mCRPC, a condition with limited therapeutic options.
Secondary objectives include:
- Comparing the efficacy of BAT and Darolutamide with ADT over SOC with ADT in terms of **PSA decline**.
- Assessing the time to **symptomatic progression** between the treatment groups.
- Evaluating **overall survival** rates in patients receiving BAT and Darolutamide with ADT compared to those receiving SOC with ADT.
Participants
The clinical trial focuses on **metastatic castration-resistant prostate cancer** and involves a study population exclusively composed of male subjects. Participants are required to be men aged 18 years and older, with a histologically-confirmed diagnosis of adenocarcinoma of the prostate. The trial does not include female subjects or vulnerable populations. The sponsor has not provided information regarding the total number of participants. Selection criteria emphasize the necessity for participants to have undergone continuous androgen ablative therapy, either through surgical castration or luteinizing hormone-releasing hormone (LHRH) agonist/antagonist, in combination with an androgen receptor inhibitor (ARI) such as Apalutamide, Darolutamide, or Enzalutamide. Participants must have documented castrate levels of serum testosterone and radiographically confirmed metastatic disease. Lifestyle considerations include the requirement for sexually active male subjects to use condoms and for their female partners of child-bearing potential to employ highly effective birth control methods during treatment and for six months thereafter. The trial does not involve any vulnerable populations, and the selection process ensures that participants have acceptable liver, renal, and hematologic function, as well as an Eastern Cooperative Oncology Group Performance status grade of 2 or lower.
Plans and Procedures
The clinical trial is designed to evaluate the efficacy of **darolutamide** in combination with bipolar androgen therapy (BAT) for patients with metastatic castration-resistant prostate cancer (mCRPC). This is a Phase II, randomized, double-blind, controlled trial. The trial aims to compare the progression-free survival (PFS) and quality of life (QoL) outcomes of the experimental treatment against the standard of care. The trial is expected to commence recruitment on July 1, 2025, and conclude by December 31, 2027.
Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to assess eligibility based on criteria such as acceptable liver and renal function, hematologic status, and documented disease progression. Following successful screening, participants will be randomized to receive either the experimental treatment or the standard of care. The trial will include regular follow-up visits to monitor treatment efficacy and safety, with assessments of PSA levels, imaging studies, and QoL evaluations using the FACIT-F scale. The end-of-study visit will occur upon completion of the treatment period or upon reaching a primary endpoint, such as disease progression or death.
The expected duration of participant involvement is contingent upon the treatment arm and individual response, with a maximum treatment period of up to 30 weeks for certain medications. Conditions that may lead to early termination from the study include significant adverse events, withdrawal of consent, or non-compliance with study protocols. The trial will adhere to rigorous ethical standards, ensuring that all participants provide informed consent and that their safety is prioritized throughout the study.
Treatment
The clinical trial involves the administration of several treatments, including both experimental and comparator medications. The **experimental medication** is **Testogel Dosiergel 16.2 mg/g Gel**, which contains the active substance **testosterone**. This medication is formulated as a **transdermal gel** and is applied via **transdermal use**. The maximum daily dose is 81 mg, with a total maximum dose of 9072 mg over a treatment period of up to 4 weeks. This hormone therapy is not a pediatric formulation and is manufactured by Besins Healthcare Germany GmbH.
Another experimental treatment is **BAY 1841788**, which contains the active substance **darolutamide**. This medication is provided as a **film-coated tablet** for **oral use**. The maximum daily dose is 1200 mg, with a total maximum dose of 268.80 g over a treatment period of up to 8 weeks. This antiandrogen is produced by Bayer AG and is not a pediatric formulation.
The study also includes several **comparator treatments**. **Abiraterone** is administered as an **oral** medication with a maximum daily dose of 1000 mg and a total maximum dose of 448000 mg over a 16-week period. This antiandrogen is not a pediatric formulation.
**Docetaxel** is another comparator, administered via **IV infusion**. The maximum daily dose is 75 mg/m², with a total maximum dose of 750 mg/m² over a 30-week period. This chemotherapy agent is not formulated for pediatric use.
**Cabazitaxel 2-propanol solvate** is also administered via **IV infusion**. The maximum daily dose is 25 mg/m², with a total maximum dose of 250 mg/m² over a 30-week period. This chemotherapy agent is not a pediatric formulation.
Lastly, **Enzalutamide** is provided as an **oral** medication with a maximum daily dose of 160 mg and a total maximum dose of 72000 mg over a 16-week period. This antiandrogen is not formulated for pediatric use.
Throughout the trial, participant compliance with dosing schedules is monitored to ensure adherence to the treatment protocols. The trial aims to evaluate the efficacy of these treatments in patients with metastatic castration-resistant prostate cancer (mCRPC), focusing on progression-free survival and quality of life outcomes.
Efficacy
The efficacy of the clinical trial titled "Darolutamide with Bipolar Androgen Therapy (BAT) for Patients with Metastatic Castration Resistant Prostate Cancer (mCRPC) – the DaroBAT Trial" will be assessed using several primary and secondary endpoints. The primary endpoints include **Progression-Free Survival (PFS)**, defined as the time from randomization to biochemical, clinical, or radiographic progression, or death from any cause, whichever occurs first, and Quality of Life (QoL) until progression, measured using the German version of the FACIT-F scale.
Secondary endpoints for efficacy evaluation include the 50% PSA response (PSA50), defined as a PSA decrease of ≥ 50% at any time compared to baseline value, the percentage of change in PSA from baseline to 12 weeks, and the maximum decline in PSA that occurs at any point after the start of treatment. Additionally, symptomatic progression-free survival, defined as the time from randomization to clinical progression or death from any cause, and Overall Survival (OS), defined as the time from randomization to death from any cause, will also be assessed.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Ability to understand and willingness to sign a written informed consent form (ICF) document
- Eastern Cooperative Oncology Group Performance status (ECOG PS) grade ≤2
- Men ≥18 years
- Histologically-confirmed adenocarcinoma of the prostate
- Treatment with continuous androgen ablative therapy (either surgical castration or luteinizing hormone-releasing hormone (LHRH)-agonist/antagonist) in combination with an ARI (Apalutamide, Darolutamide, or Enzalutamide, as currently approved for mCSPC)
- Documented castrate level of serum testosterone (<50 ng/dl)
- Metastatic disease radiographically documented by CT/MRI, bone scan or PSMA-PET-CT
- Disease progression while on Apalutamide, Darolutamide or Enzalutamide as currently approved based on: PSA progression defined as an over 25% increase in PSA, as determined within two consecutive measurements separated by at least one week and/or Radiographic disease progression, based on RECIST 1.1 in patients with measurable soft tissue lesions, or PCWG3 for patients with bone disease
- Screening PSA ≥ 1.0 ng/mL
- Acceptable liver function: •Bilirubin ≤ institutional upper limit of normal (ULN) •aspartate aminotransferase (AST/SGOT) and alanine aminotransferase (ALT/SGPT) < 1.5 times ULN
- Acceptable renal function: •Serum creatinine < 2.0 times ULN
- Acceptable hematologic status: •Absolute neutrophil count (ANC) ≥ 1500 cells/mm3 (1.5 ×109/L) •Platelet count ≥ 100,000 platelet/mm3 (100 ×109/L) •Hemoglobin ≥ 9 g/dL
- At least 4 weeks since prior radiation
- Sexually active male subjects must agree to use condoms as an effective barrier method and refrain from sperm donation, and their female partners of child-bearing potential to use a method of highly effective birth control during treatment and for 6 months thereafter
Exclusion Criteria
- Pain due to metastatic prostate cancer > NRS 3 and/or requiring the onset or escalation of opioid treatment. Note: Patients should be on a stable dose for at least four weeks.
- Prior systemic treatment for mCRPC
- Hepatic metastases and/or evidence of disease in sites or extent that, in the opinion of the investigator, would put the patient at risk from therapy with testosterone (e.g., femoral metastases with concern over fracture risk, severe and extensive spinal metastases with concern over spinal cord compression, progression on first line antihormonal therapy within 6 months)
- Any of the following within 6 months before randomization: stroke, myocardial infarction, severe/unstable angina pectoris, coronary/peripheral artery bypass graft, congestive heart failure (New York Heart Association Class III or IV)
- Evidence of serious and/or unstable pre-existing medical, psychiatric or other condition (including laboratory abnormalities) that could interfere with patient safety or provision of informed consent to participate in this study
- Active uncontrolled infection, including known history of HIV/AIDS or hepatitis B or C
- Any psychological, familial, sociological, or geographical condition that could potentially interfere with compliance with the study protocol and follow-up schedule
- Prior history of a thromboembolic event within the last 12 months that is not being treated with systemic anticoagulation
- Uncontrolled hypertension as indicated by a resting systolic blood pressure (BP) ≥ 160 mmHg or diastolic BP ≥ 100 mmHg despite medical treatment
- Major surgery (e.g., requiring general anesthesia) within 4 weeks before screening, or patients not fully recovered from prior surgery (i.e., unhealed wound). Note: subjects with planned surgical procedures to be conducted under local anesthesia may participate
- Known BRCA-mutations
- Known hypersensitivity to any of the study drugs, study drug classes, or excipients in the formulation of the study drugs
- Long QT-syndrome
- Thrombophilia
- Migraine
- History of seizures
- Prior malignancy, except prostate cancer, adequately treated basal cell or squamous cell carcinoma of skin or superficial bladder cancer or cancer for which treatment has been completed ≥ 5 years before randomization and from which the participant has been disease-free
- Active brain metastases. Note: Subjects with treated, asymptomatic and clinically stable metastases are eligible.
- Current participation in any other clinical trial or use of any other IMP within the last 30 days prior to screening visit or within 5 half-lives of the IMP (whichever is longer) and throughout the trial
- Any dependent relationship of the subject with the investigator, trial site or sponsor/sponsor’s delegate (e.g., employees or relatives)
- Institutionalization because of legal or regulatory order
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Germany | Recruiting | 01 Jul 2025 | 60 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
ABIRATERONE | Comparator | PHF00245MIG | ORAL USE | 1000 | 16 | SCP132446 |
Testogel Dosiergel 16,2 mg/g Gel | Test | GEL | TRANSDERMAL USE | 81 | 4 | PRD9058939 |
DOCETAXEL | Comparator | PHF00230MIG | IV INFUSION | 75 | 30 | SCP126226 |
ENZALUTAMIDE | Comparator | PHF00007MIG | ORAL USE | 160 | 16 | SCP104122323 |
BAY 1841788 | Test | FILM-COATED TABLET | ORAL USE | 1200 | 8 | PRD1849573 |
CABAZITAXEL | Comparator | PHF00230MIG | IV INFUSION | 25 | 30 | SCP191833 |