A trial to learn how well darolutamide plus androgen deprivation therapy (ADT) works in comparison to placebo plus ADT in men with prostate cancer that has spread to other parts of their body

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Bayer Consumer Care AG, Bayer AG

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male

Therapeutic area

Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]

Trial duration

22 Feb 2021 → 23 Jan 2026

Decision date (initial)

2023-05-20

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Bayer Consumer Care AG, Switzerland

External identifiers

EU CT number

2022-502244-12-00

EudraCT number

2020-003093-48

ClinicalTrials.gov

NCT04736199

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Efficacy, Pharmacogenetic, Safety, Pharmacodynamic, Others

To determine if darolutamide in addition to ADT is superior to placebo plus ADT by improving rPFS in participants with mHSPC.

Secondary objectives 3

1. To evaluate efficacy of darolutamide in addition to ADT compared to placebo plus ADT by improving OS, time to progress to CRPC, time to initiation of subsequent anti-cancer therapy, time to PSA progression, and undetectable PSA rates
2. To estimate the participant’s quality of life benefit of darolutamide in addition to ADT compared to placebo plus ADT by improving symptomatic time to pain progression
3. To assess the safety of darolutamide in addition to ADT compared to placebo plus ADT in participants with mHSPC

Conditions and MedDRA coding

Metastatic hormone-sensitive prostate cancer (mHSPC)

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

Plan to share IPD

No

IPD plan description

Availability of this study's data will later be determined according to Bayer's commitment to the EFPIA/PhRMA "Principles for responsible clinical trial data sharing". This pertains to scope, timepoint and process of data access. As such, Bayer commits to sharing upon request from qualified researchers patient-level clinical trial data, study-level clinical trial data, and protocols from clinical trials in patients for medicines and indications approved in the US and EU as necessary for conducting legitimate research. This applies to data on new medicines and indications that have been approved by the EU and US regulatory agencies on or after January 01, 2014. Interested researchers can use www.vivli.org to request access to anonymized patient-level data and supporting documents from clinical studies to conduct research. Information on the Bayer criteria for listing studies and other relevant information is provided in the member section of the portal.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 10

1. Written informed consent obtained. Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the ICF and in this protocol.
2. Males ≥18 years of age.
3. Histologically or cytologically confirmed adenocarcinoma of prostate.
4. Documented metastatic disease by conventional imaging method either by a positive 99mTc-phosphonate bone scan, or soft tissue or visceral metastases, either by contrastenhanced abdominal/pelvic/chest CT or MRI scan assessed by central review. Note: Metastatic disease is defined as either malignant lesions in bone scan or measurable lymph nodes above the aortic bifurcation or soft tissue/visceral lesions according to RECIST version 1.1. Lymph nodes are measurable if the short axis diameter is ≥15 mm, soft tissue/visceral lesions are measurable if the long axis diameter is ≥10 mm. Regional lymph node metastases only (N1, below the aortic bifurcation) will not be considered as metastases eligible for the study. Only participants with non-regional lymph node metastases (M1a) and/or bone metastases (M1b) and/or other sites of metastases with or without bone disease (M1c), assessed according to National Comprehensive Cancer Network (NCCN) classification, will be eligible.
5. Started ADT (LHRH agonist/antagonist or orchiectomy) with or without first generation anti–androgen, but no longer than 12 weeks before randomization. For participants receiving LHRH agonists, treatment in combination with a first generation anti–androgen for at least 14 days prior to randomization is recommended.
6. First generation anti–androgen must be discontinued at least 1 day before study treatment start.
7. Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0, 1 or 2.
8. Blood counts at Screening: hemoglobin ≥9.0 g/dL, absolute neutrophil count ≥1.5x10^9/L, platelet count ≥100x10^9/L (participant must not have received any growth factor within 4 weeks or a blood transfusion within 7 days of the hematology laboratory sample obtained at Screening).
9. Screening values of serum alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) ≤1.5 x ULN, total bilirubin ≤1.5 x ULN, creatinine ≤2.0 x ULN.
10. Sexually active male participants must agree to use condoms as an effective barrier method and refrain from sperm donation, and/or their female partners of reproductive potential to use a method of effective birth control, during the treatment with study drug/placebo and for 4 weeks after treatment with study drug/placebo.

Exclusion criteria 14

1. Pathological finding consistent with small cell, ductal or neuroendocrine carcinoma of the prostate
2. Known brain/ leptomeningeal metastases Note: Brain CT/MRI scan should be performed only in case of symptoms.
3. "Prior treatment with: - LHRH agonist/antagonists started >12 weeks before randomization starts except neoadjuvant and /or adjuvant therapy for a duration ≤ 24 months and completed ≥ 12 months prior to randomization - Second–generation androgen receptor (AR) inhibitors such as enzalutamide, darolutamide, apalutamide or other investigational AR inhibitors - Cytochrome P 17 enzyme inhibitor such as abiraterone acetate or oral ketoconazole as anti-cancer treatment for prostate cancer - Chemotherapy including docetaxel or immunotherapy for prostate cancer - Use of systemic corticosteroid with dose greater than the equivalent 10 mg of prednisone/day within 28 days prior to randomization - radiopharmaceuticals - Any other anti-cancer treatment for prostate cancer, excluding local therapies and ADT"
4. Treatment with radiotherapy (external beam radiation therapy [EBRT], brachytherapy) within 2 weeks before randomization.
5. Known hypersensitivity to any of the study drugs, study drug classes, or excipients in the formulation of the study drugs.
6. Contraindication to iodinated CT and gadolinium chelate MRI intravenous contrast agent(s).
7. Any prior malignancy (other than adequately treated basal cell or squamous cell skin cancer, superficial bladder cancer, or any other cancer in situ currently in complete remission) within 5 years prior to randomization.
8. An active viral hepatitis (defined as Hepatitis B surface antigen [HBsAg] reactive or detectable [qualitative] hepatitis B virus [HBV] DNA or defined as hepatitis C virus [HCV] ribonucleic acid [RNA] [qualitative] is detected), known human immunodeficiency virus (HIV) infection with detectable viral load, or chronic liver disease with a need of treatment. Note: No testing for Hepatitis B and/or Hepatitis C is required unless mandated by local authority. No HIV testing is required unless mandated by local authority.
9. Had 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).
10. Uncontrolled hypertension as indicated by a resting systolic BP ≥ 160 mmHg or diastolic BP ≥ 100 mmHg despite medical management.
11. A gastrointestinal (GI) disorder or procedure which is expected to interfere significantly with absorption of study drug.
12. Previous (within 28 days before the start of study drug or 5 half–lives of the investigational treatment of the previous study, whichever is longer) or concomitant participation in another clinical study with investigational medicinal product(s).
13. Any other serious or unstable illness, or medical, social, or psychological condition, that could jeopardize the safety of the participant and/or his/her compliance with study procedures or may interfere with the participant’s participation in the study or evaluation of the study results.
14. Inability to swallow oral medications.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Radiological progression-free survival

Secondary endpoints 7

1. Overall survival (OS)
2. Time to castration–resistant prostate cancer (CRPC)
3. Time to initiation of subsequent anti-cancer therapy
4. Time to PSA progression
5. Percentage of participants with detectable PSA values (≥0.2 ng/mL) at baseline which become undetectable (<0.2 ng/mL)
6. Time to pain progression
7. Number of participants with treatment emergent adverse events

Investigational products

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

Test 1

Placebo 1

Auxiliary 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Bayer Consumer Care AG

Sponsor organisation

Bayer Consumer Care AG

Address

Peter Merian-Strasse 84

City

Basel

Postcode

4052

Country

Switzerland

Scientific contact point

Organisation

Bayer AG

Contact name

Therapeutic Area Head

Public contact point

Organisation

Bayer AG

Contact name

Therapeutic Area Head

Third parties 2

Bayer AG

Sponsor organisation

Bayer AG

Address

-

City

Leverkusen

Postcode

51368

Country

Germany

Sponsor responsibilities

Article 77 compliance

Bayer Consumer Care AG

Article 77 implementation

Bayer Consumer Care AG

Locations

3 EU/EEA countries · 16 investigational sites

By country

Investigational sites

Country notifications

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

Results and documents

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

Documents 16 files

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

Application history

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