Efficacy and Safety Study of Darolutamide (ODM-201) in Men With High-risk Non-metastatic Castration-resistant Prostate Cancer (ARAMIS)

Bayer

Status and phase: Completed; Phase 3

Conditions: Castration-Resistant; Prostate Cancer Non-Metastatic

Treatments: Drug: Darolutamide (Nubeqa, BAY1841788); Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT02200614

17712

2013-003820-36 (EudraCT Number)

Details and patient eligibility

About

The purpose of this study is to assess the safety and efficacy of BAY1841788 (ODM-201) in patients with non-metastatic castration-resistant prostate cancer.

Enrollment: 1,509 patients

Sex: Male

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Histologically or cytologically confirmed adenocarcinoma of prostate without neuroendocrine differentiation or small cell features.
• Castration-resistant prostate cancer (CRPC) with castrate level of serum testosterone.
• Prostate-specific Antigen (PSA) doubling time of ≤ 10 months and PSA > 2ng/ml.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
• Blood counts at screening: haemoglobin ≥ 9.0 g/dl,absolute neutrophil count ≥ 1500/µl, platelet count ≥ 100,000/µl.
• Screening values of serum alanine aminotransferase (ALT) and/or aspartate transaminase (AST) ≤ 2.5 x upper limit of normal (ULN), total bilirubin ≤ 1.5 x ULN, creatinine ≤ 2.0 x ULN.
• Sexually active patients, unless surgically sterile, must agree to use condoms as an effective barrier method and refrain from sperm donation during the study treatment and for 3 months after the end of the study treatment.

Exclusion criteria

• History of metastatic disease at any time or presence of detectable metastases.
• Acute toxicities of prior treatments and procedures not resolved to grade ≤ 1 or baseline before randomisation.
• Prior treatment with: second generation androgen receptor (AR) inhibitors, other investigational AR inhibitors, or CYP17 enzyme inhibitor.
• Use of estrogens or 5-α reductase inhibitors or AR inhibitors.
• Prior chemotherapy or immunotherapy for prostate cancer.
• Use of systemic corticosteroid.
• Radiation therapy within 12 weeks before randomisation.
• Severe or uncontrolled concurrent disease, infection or co-morbidity.
• Treatment with bisphosphonate or denosumab within 12 weeks before randomisation.
• Known hypersensitivity to the study treatment or any of its ingredients.
• Major surgery within 28 days before randomisation.
• Any of the following within 6 months before randomisation: stroke, myocardial infarction, severe/unstable angina pectoris, coronary/peripheral artery bypass graft; congestive heart failure New York Heart Association (NYHA) Class III or IV.
• Uncontrolled hypertension.
• Prior malignancy.
• Gastrointestinal disorder or procedure which expects to interfere significantly with absorption of study treatment.
• Active viral hepatitis, active human immunodeficiency virus (HIV) or chronic liver disease.
• Treatment with any investigational drug within 28 days before randomisation.
• Any condition that in the opinion of the investigator would impair the patients' ability to comply with the study procedures.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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1,509 participants in 2 patient groups, including a placebo group

Darolutamide (BAY1841788)

Experimental group

Description:

Participants received Darolutamide 600 mg (2 tablets of 300 mg) twice daily with food, equal to a total daily dose of 1200 mg.

Treatment:

Drug: Darolutamide (Nubeqa, BAY1841788)

Placebo

Placebo Comparator group

Description:

Participants received matching placebo 2 tablets twice daily with food.

Treatment:

Drug: Placebo