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Darolutamide in Addition to ADT Versus ADT in Metastatic Hormone-sensitive Prostate Cancer

Phase 3
Active, not recruiting
Conditions
Prostatic Neoplasms
Interventions
Drug: Placebo
Other: Androgen deprivation therapy (ADT)
Registration Number
NCT04736199
Lead Sponsor
Bayer
Brief Summary

The purpose of the study is to assess the efficacy and safety of darolutamide in combination with standard androgen deprivation therapy (ADT) in patients with metastatic hormone sensitive prostate cancer.

Detailed Description

Not available

Recruitment & Eligibility

Status
ACTIVE_NOT_RECRUITING
Sex
Male
Target Recruitment
662
Inclusion Criteria
  • Histologically or cytologically confirmed adenocarcinoma of prostate
  • Metastatic disease
  • Started ADT (LHRH agonist/antagonist or orchiectomy) with or without first generation anti-androgen, but not earlier than 12 weeks before randomization
  • Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0, 1 or 2
  • Adequate bone marrow, liver and renal function
Exclusion Criteria
  • Prior treatment with: LHRH agonist/antagonists except neoadjuvant and /or adjuvant therapy; Second-generation androgen receptor (AR) inhibitors such as enzalutamide, darolutamide, apalutamide or other investigational AR inhibitors; Cytochrome P17 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.
  • Treatment with radiotherapy within 2 weeks before randomization
  • Contraindication to iodinated CT and gadolinium chelate MRI intravenous contrast agent(s)
  • 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)
  • Uncontrolled hypertension as indicated by a resting systolic BP ≥ 160 mmHg or diastolic BP ≥ 100 mmHg despite medical management
  • A gastrointestinal (GI) disorder or procedure which is expected to interfere significantly with absorption of study drug
  • 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
  • Inability to swallow oral medications

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Darolutamide+ADTAndrogen deprivation therapy (ADT)Participants will receive darolutamide 600 mg (2 tablets of 300 mg) twice daily with food and ADT of investigator's choice as standard therapy
Placebo+ADTPlaceboParticipants will receive placebo twice daily with food and ADT of investigator's choice as standard therapy
Placebo+ADTAndrogen deprivation therapy (ADT)Participants will receive placebo twice daily with food and ADT of investigator's choice as standard therapy
Darolutamide+ADTDarolutamide (Nubeqa, BAY1841788)Participants will receive darolutamide 600 mg (2 tablets of 300 mg) twice daily with food and ADT of investigator's choice as standard therapy
Primary Outcome Measures
NameTimeMethod
Radiological progression-free survival (rPFS)36 months

Time from the date of randomization to the date of first documentation of radiological progressive disease or death due to any cause, whichever occurs first.

Secondary Outcome Measures
NameTimeMethod
Overall survival (OS)Up to 55 months

Time from the date of randomization to the date of death from any cause.

Time to castration-resistant prostate cancer (CRPC)Up to 55 months

Time from the date of randomization to the date of first castration resistant event (radiological progression, PSA progression or symptomatic skeletal events, whichever occurs first).

Time to initiation of subsequent anti-cancer therapyUp to 55 months

Time from the date of randomization to initiation of first subsequent anti-cancer therapy for prostate cancer.

Time to PSA progressionUp to 55 months

Time from the date of randomization to the date of first prostate-specific antigen (PSA) progression. PSA progression is defined as a ≥25% increase above the nadir (lowest Screening or baseline) value, which is confirmed by a second value 3 or more weeks later, and an increase in absolute value of ≥ 2 ng/mL above nadir, at least 12 weeks from baseline.

PSA undetectable rates (<0.2 ng/mL)Up to 55 months

The percentage of participants with detectable PSA values (≥0.2 ng/mL) at baseline which become undetectable (\<0.2 ng/mL) during the study treatment.

Time to pain progressionUp to 55 months

Time from the date of randomization to pain progression, where progression is defined as an increase of 2 or more points from baseline. Pain to be assessed with a patient reported questionaire.

Number of participants with adverse events as a measure of safetyUp to 55 months

Trial Locations

Locations (131)

Nepean Hospital

🇦🇺

Kingswood, New South Wales, Australia

Northern Cancer Institute

🇦🇺

St Leonards, New South Wales, Australia

Macquarie University Hospital

🇦🇺

Sydney, New South Wales, Australia

Cancer Research South Australia

🇦🇺

Adelaide, South Australia, Australia

Peninsula Oncology Centre

🇦🇺

Frankston, Victoria, Australia

Austin Health

🇦🇺

Heidelberg, Victoria, Australia

Assistência Multidisciplinar em Oncologia (AMO)

🇧🇷

Salvador, Bahia, Brazil

Hosp. Araujo Jorge da Associação de Combate ao Câncer

🇧🇷

Goiânia, Goiás, Brazil

Hospital da Universidade Federal de Minas Gerais

🇧🇷

Belo Horizonte, Minas Gerais, Brazil

Cetus Oncologia Hospital Dia

🇧🇷

Belo Horizonte, Minas Gerais, Brazil

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Nepean Hospital
🇦🇺Kingswood, New South Wales, Australia
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