Clinical trial NCT02200614: Efficacy and Safety Study of Darolutamide (ODM-201) in Men With High-risk Non-metastatic Castration-resistant Prostate Cancer
Official title: A Multinational, Randomised, Double-blind, Placebo-controlled, Phase III Efficacy and Safety Study of Darolutamide (ODM-201) in Men With High-risk Non-metastatic Castration-resistant Prostate Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Prostate Cancer Non-Metastatic
Castration-Resistant
Lead sponsor: Bayer
Sponsor class: INDUSTRY
Collaborators: name: Orion Corporation, Orion Pharma
First posted: 2014-07-25
Enrollment: 1509
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Metastasis-Free Survival
timeFrame: From randomization to the time approximately 385 MFS events were observed (approximately 48 months)
Secondary outcomes:
measure: Overall Survival - Primary Analysis
timeFrame: From randomization of the first subject to the time approximatively 140 death events were observed (approximately 48 months)
measure: Time to Pain Progression - Primary Analysis
timeFrame: From randomization until last study treatment (assessed every 4 months) (approximately 48 months)
measure: Time to Initiation of First Cytotoxic Chemotherapy for Prostate Cancer - Primary Analysis
timeFrame: From randomization until last study treatment (assessed every 4 months) (approximately 48 months)
measure: Time to First Symptomatic Skeletal Event (SSE) - Primary Analysis
timeFrame: From randomization until last study treatment (assessed every 4 months) (approximately 48 months)
measure: Overall Survival - Final Analysis
timeFrame: From randomization of the first subject to the time approximatively 254 death events were observed (approximately 56 months)
measure: Time to Pain Progression - Final Analysis
timeFrame: From randomization until last study treatment (assessed every 4 months) (approximately 48 months)
measure: Time to Initiation of First Cytotoxic Chemotherapy for Prostate Cancer - Final Analysis
timeFrame: From randomization until initiation of first cytotoxic chemotherapy treatment (approximately 59 months)
measure: Time to First Symptomatic Skeletal Event (SSE) - Final Analysis
timeFrame: From randomization until occurrence of first SSE event (approximately 59 months)
Other outcomes:
Locations:
city: Homewood
country: United States
state: Alabama
city: Anchorage
country: United States
state: Alaska
city: Tucson
country: United States
state: Arizona
city: Fountain Valley
country: United States
state: California
city: La Jolla
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state: California
city: Laguna Hills
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state: California
city: Los Angeles
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state: California
city: Los Angeles
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state: California
city: San Diego
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city: Denver
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city: Orlando
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city: Port Saint Lucie
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city: Coeur d'Alene
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state: Idaho
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state: Kansas
city: New Orleans
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city: Annapolis
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state: Maryland
city: Baltimore
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city: Grand Rapids
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state: Michigan
city: Royal Oak
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state: Michigan
city: Omaha
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state: Nebraska
city: Omaha
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city: Toyama
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city: Cheongju
country: Korea, Republic of
state: Chungcheongbugdo
city: Gwangju
country: Korea, Republic of
state: Gwangju Gwang''yeogsi
city: Seoul
country: Korea, Republic of
state: Seoul Teugbyeolsi
city: Seoul
country: Korea, Republic of
state: Seoul Teugbyeolsi
city: Daegu
country: Korea, Republic of
city: Daegu
country: Korea, Republic of
city: Incheon
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city: Seoul
country: Korea, Republic of
city: Seoul
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city: Seoul
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city: Seoul
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city: Daugavpils
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city: Leipaja
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city: Riga
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city: Riga
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city: Kaunas
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city: Kaunas
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city: La Victoria
country: Peru
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city: Elche
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state: Andalucía
city: L'Hospitalet de Llobregat
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state: Barcelona
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country: Spain
state: Barcelona
city: Terrassa
country: Spain
state: Barcelona
city: Jerez de la Frontera
country: Spain
state: Cádiz
city: Manacor
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state: Illes Baleares
city: Palma de Mallorca
country: Spain
state: Illes Baleares
city: Alcorcón
country: Spain
state: Madrid
city: Bilbao
country: Spain
state: Vizcaya
city: Barcelona
country: Spain
city: Barcelona
country: Spain
city: Córdoba
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city: Granada
country: Spain
city: Lugo
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city: Madrid
country: Spain
city: Madrid
country: Spain
city: Madrid
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city: Madrid
country: Spain
city: Málaga
country: Spain
city: Salamanca
country: Spain
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country: Spain
city: Sevilla
country: Spain
city: Valencia
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city: Valencia
country: Spain
city: Valencia
country: Spain
city: Göteborg
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city: Stockholm
country: Sweden
city: Uppsala
country: Sweden
city: Örebro
country: Sweden
city: Kaohsiung City ,
country: Taiwan
city: Kaoshiung
country: Taiwan
city: Taichung
country: Taiwan
city: Taipei
country: Taiwan
city: Taoyuan
country: Taiwan
city: Ankara
country: Turkey
city: Istanbul
country: Turkey
city: Izmir
country: Turkey
city: Izmir
country: Turkey
city: Manisa
country: Turkey
city: Sivas
country: Turkey
city: Chernivtsi
country: Ukraine
city: Dnipro
country: Ukraine
city: Kharkiv
country: Ukraine
city: Kryvyi Rih
country: Ukraine
city: Kyiv
country: Ukraine
city: Kyiv
country: Ukraine
city: Uzhgorod
country: Ukraine
city: Zaporozhye
country: Ukraine
city: Reading
country: United Kingdom
state: Berkshire
city: Llanelli
country: United Kingdom
state: Carmarthenshire
city: Romford
country: United Kingdom
state: Essex
city: Stevenage
country: United Kingdom
state: Hertfordshire
city: Dartford
country: United Kingdom
state: Kent
city: Maidstone
country: United Kingdom
state: Kent
city: Preston
country: United Kingdom
state: Lancashire
city: Bebington
country: United Kingdom
state: Merseyside
city: Scunthorpe
country: United Kingdom
state: North East Lincolnshire
city: Bath
country: United Kingdom
state: Somerset
city: Stoke-on-Trent
country: United Kingdom
state: Staffordshire
city: Dudley
country: United Kingdom
state: West Midlands
city: Huddersfield
country: United Kingdom
state: West Yorkshire
city: Wakefield
country: United Kingdom
state: West Yorkshire
city: Cardiff
country: United Kingdom
city: Glasgow
country: United Kingdom
city: London
country: United Kingdom
Study officials:
affiliation: Bayer
name: Bayer Study Director
role: STUDY_DIRECTOR
References:
citation: Chowdhury S, Oudard S, Uemura H, Joniau S, Dearden L, Capone C, Van Sanden S, Diels J, Hadaschik BA. Apalutamide Compared with Darolutamide for the Treatment of Non-metastatic Castration-Resistant Prostate Cancer: Efficacy and Tolerability in a Matching-Adjusted Indirect Comparison. Adv Ther. 2022 Jan;39(1):518-531. doi: 10.1007/s12325-021-01885-6. Epub 2021 Nov 19.
citation: Fizazi K, Blue I, Nowak JT. Darolutamide and survival in nonmetastatic, castration-resistant prostate cancer: a patient perspective of the ARAMIS trial. Future Oncol. 2021 May;17(14):1699-1707. doi: 10.2217/fon-2020-1291. Epub 2021 Feb 8.
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