Darolutamide and bipolar androgen therapy for mCRPC patients (DaroBAT)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Universitaet Muenster

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male

Therapeutic area

Diseases [C] - Male Urogenital Diseases [C12], Diseases [C] - Neoplasms [C04]

Trial duration

6 Aug 2025 → ongoing

Decision date (initial)

2025-07-24

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Bayer Vital GmbH

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety, Therapy

To compare the efficacy in Progression Free Survival (PFS) and Quality of Life of bipolar androgen therapy and Darolutamide in addition to androgen deprivation therapy (ADT) over Standard Of Care in addition to ADT.

Secondary objectives 3

1. To compare the efficacy of BAT and Darolutamide in addition to ADT over SOC in addition to ADT regarding PSA decline
2. To compare the efficacy of BAT and Darolutamide in addition to ADT over SOC in addition to ADT regarding time to symptomatic progression
3. To compare the efficacy of BAT and Darolutamide in addition to ADT over SOC in addition to ADT regarding overall survival

Conditions and MedDRA coding

metastatic castration-resistant prostate cancer

Regulatory references

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 14

1. Ability to understand and willingness to sign a written informed consent form (ICF) document
2. Eastern Cooperative Oncology Group Performance status (ECOG PS) grade ≤2
3. Men ≥18 years
4. Histologically-confirmed adenocarcinoma of the prostate
5. 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)
6. Documented castrate level of serum testosterone (<50 ng/dl)
7. Metastatic disease radiographically documented by CT/MRI, bone scan or PSMA-PET-CT
8. 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
9. Screening PSA ≥ 1.0 ng/mL
10. Acceptable liver function: •Bilirubin ≤ institutional upper limit of normal (ULN) •aspartate aminotransferase (AST/SGOT) and alanine aminotransferase (ALT/SGPT) < 1.5 times ULN
11. Acceptable renal function: •Serum creatinine < 2.0 times ULN
12. 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
13. At least 4 weeks since prior radiation
14. 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 21

1. Pain due to metastatic prostate cancer > NRS 3 and/or requiring opioid treatment
2. Prior systemic treatment for mCRPC
3. Visceral 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)
4. 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)
5. 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
6. Active uncontrolled infection, including known history of HIV/AIDS or hepatitis B or C
7. Any psychological, familial, sociological, or geographical condition that could potentially interfere with compliance with the study protocol and follow-up schedule
8. Prior history of a thromboembolic event within the last 12 months that is not being treated with systemic anticoagulation
9. Uncontrolled hypertension as indicated by a resting systolic blood pressure (BP) ≥ 160 mmHg or diastolic BP ≥ 100 mmHg despite medical treatment
10. 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
11. Known BRCA-mutations
12. Known hypersensitivity to any of the study drugs, study drug classes, or excipients in the formulation of the study drugs
13. Long QT-syndrome
14. Thrombophilia
15. Migraine
16. History of seizures
17. Prior malignancy, except prostate cancer, adequately treated basal cell or squamous cell carcinoma of skin or superficial bladder cancer (pTa) or cancer for which treatment has been completed ≥ 5 years before randomization and from which the participant has been disease-free
18. Brain metastases
19. 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
20. Any dependent relationship of the subject with the investigator, trial site or sponsor/sponsor’s delegate (e.g., employees or relatives)
21. Institutionalization because of legal or regulatory order

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. PFS defined as time from randomization to biochemical, clinical, or radiographic progression, or death from any cause, whichever occurs first.
2. QoL until progression measured using the German version of the FACIT-F scale

Secondary endpoints 5

1. 50% PSA response (PSA50) defined as a PSA decrease of ≥ 50% at any time compared to baseline value
2. Percentage of change in PSA from baseline to 12 weeks
3. Maximum decline in PSA that occurs at any point after start of treatment
4. Symptomatic progression-free survival defined as time from randomization to clinical progression or death from any cause, whichever occurs first.
5. Overall Survival (OS) defined as time from randomization to death from any cause

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Comparator 4

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Universitaet Muenster

Sponsor organisation

Universitaet Muenster

Address

Schlossplatz 2, Schlossbezirk Schlossbezirk

City

Muenster

Postcode

48149

Country

Germany

Scientific contact point

Organisation

Universitaet Muenster

Contact name

Dr. Katrin Schlack

Public contact point

Organisation

Universitaet Muenster

Contact name

Dr. Katrin Schlack

Locations

1 EU/EEA country · 5 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Urgent safety measures 1 · Art. 54 CTR

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 15 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications