Clinical trial NCT02799602: Darolutamide in Addition to Standard Androgen Deprivation Therapy and Docetaxel in Metastatic Hormone-Sensitive Prostate Cancer
Official title: A Randomized, Double-blind, Placebo Controlled Phase III Study of Darolutamide (ODM-201) Versus Placebo in Addition to Standard Androgen Deprivation Therapy and Docetaxel in Patients With Metastatic Hormone Sensitive Prostate Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Metastatic Hormone-sensitive Prostate Cancer
Lead sponsor: Bayer
Sponsor class: INDUSTRY
Collaborators: name: Orion Corporation, Orion Pharma
First posted: 2016-06-15
Enrollment: 1306
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 the study is to assess the efficacy and safety of BAY1841788 (darolutamide (ODM-201)) in combination with standard androgen deprivation therapy (ADT) and docetaxel in patients with metastatic hormone sensitive prostate cancer.

Detailed description: This is a randomized, double-blind, placebo-controlled, multicenter phase III study. The study population will consist of approximately 1300 subjects with metastatic hormone sensitive prostate cancer (mHSPC), who will be randomized (1:1 ratio) to receive 600 mg (2 x 300 mg tablets) of darolutamide (ODM-201)/placebo twice daily with food, equivalent to a total daily dose of 1200 mg, in addition to standard androgen deprivation therapy (ADT) and docetaxel. Subjects will be stratified at randomization for the extent of disease and for Alkaline Phosphatase levels. All subjects will be treated with ADT as standard therapy. Six cycles of docetaxel will be administered after randomization.

The subjects considered for inclusion in the study will have metastatic prostate cancer and will be candidates for ADT and docetaxel.

Treatment with darolutamide (ODM-201)/placebo will be administered until symptomatic progressive disease, change of antineoplastic therapy, unacceptable toxicity, until subject withdraws consent, withdrawal from the study at the discretion of the investigator or his/her designated associate(s), death, non-compliance, or if sponsor terminates the study.

Eligibility criteria: Inclusion Criteria:

* Histologically or cytologically confirmed adenocarcinoma of prostate.
* Metastatic disease
* Candidates for ADT and docetaxel.
* Started ADT with or without first generation anti androgen, but no longer than 12 weeks before randomization
* An Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
* Adequate bone marrow, liver and renal function

Exclusion Criteria:

* Prior treatment with: LHRH agonist/antagonists; second generation androgen receptor (AR) inhibitors such as enzalutamide, ARN-509, darolutamide (ODM-201), other investigational AR inhibitors; CYP17 enzyme inhibitor such as abiraterone acetate or oral ketoconazole as antineoplastic treatment for prostate cancer; chemotherapy or immunotherapy for prostate cancer prior to randomization.
* Treatment with radiotherapy/radiopharmaceuticals within 2 weeks before randomization.
* 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)
* Had a prior malignancy. Adequately treated basal cell or squamous cell carcinoma of skin or superficial bladder cancer that has not spread behind the connective tissue layer (i.e., pTis, pTa, and pT1) is allowed, as well as any other cancer for which treatment has been completed 5 years before randomization and from which the subject has been disease-free
* Gastrointestinal disorder or procedure which is expected to interfere significantly with absorption of study treatment.
* Inability to swallow oral medications

Primary outcomes:
measure: OS From Date of Randomization Until Death From Any Cause - Number of Events
timeFrame: From randomization of the first participant until death from any cause up to 25 OCT 2021 cut-off date 533 OS events were reached (approximate 59 months)
measure: OS From Date of Randomization Until Death From Any Cause - Month
timeFrame: From randomization of the first participant until death from any cause up to 25 OCT 2021 cut-off date 533 OS events were reached (approximate 59 months)
Secondary outcomes:
measure: Number of Participants With TEAEs
timeFrame: From the first dose of darolutamide or placebo until 30 days after the last dose of darolutamide or placebo administration up to cut-off date for the final completion analysis 11 APR 2023 (approximately 77 months)
measure: Time to Castration-Resistant Prostate Cancer (CRPC) - Number of Events
timeFrame: From randomization of the first participant to the first occurrence of an CRPC event up to 25 OCT 2021 cut-off date approximately 59 months
measure: Time to Castration-Resistant Prostate Cancer (CRPC) - Month
timeFrame: From randomization of the first participant to the first occurrence of an CRPC event up to 25 OCT 2021 cut-off date approximately 59 months
measure: Time to Pain Progression - Number of Events
timeFrame: From randomization of the first participant to the first occurrence of a pain progression event up to 25 OCT 2021 cut-off date approximately 59 months
measure: Time to Pain Progression - Month
timeFrame: From randomization of the first participant to the first occurrence of a pain progression event up to 25 OCT 2021 cut-off date approximately 59 months
measure: Symptomatic Skeletal Event Free Survival (SSE-FS) - Number of Events
timeFrame: From randomization of the first participant to the first occurrence of an SSE event or death from any cause, whichever occurred first up to 25 OCT 2021 cut-off date approximately 59 months
measure: Symptomatic Skeletal Event Free Survival (SSE-FS) - Month
timeFrame: From randomization of the first participant to the first occurrence of an SSE event or death from any cause, whichever occurred first up to 25 OCT 2021 cut-off date approximately 59 months
measure: Time to First Symptomatic Skeletal Event (SSE) - Number of Events
timeFrame: From randomization of the first participant to the first occurrence of an SSE event up to 25 OCT 2021 cut-off date approximately 59 months
measure: Time to First Symptomatic Skeletal Event (SSE) - Month
timeFrame: From randomization of the first participant to the first occurrence of an SSE event up to 25 OCT 2021 cut-off date approximately 59 months
measure: Time to Initiation of Subsequent Antineoplastic Therapy - Number of Events
timeFrame: From randomization of the first participant to the initiation of first subsequent systemic antineoplastic therapy up to 25 OCT 2021 cut-off date approximately 59 months
measure: Time to Initiation of Subsequent Antineoplastic Therapy - Month
timeFrame: From randomization of the first participant to the initiation of first subsequent systemic antineoplastic therapy up to 25 OCT 2021 cut-off date approximately 59 months
measure: Time to Worsening of Disease-Related Physical Symptoms - Number of Events
timeFrame: From randomization of the first participant to the first increase in disease-related physical symptoms based on the NCCN-FACT-FPSI-17 questionnaire up to 25 OCT 2021 cut-off date approximately 59 months
measure: Time to Worsening of Disease-Related Physical Symptoms - Month
timeFrame: From randomization of the first participant to the first increase in disease-related physical symptoms based on the NCCN-FACT-FPSI-17 questionnaire up to 25 OCT 2021 cut-off date approximately 59 months
measure: Time to Initiation of Opioid Use for ≥7 Consecutive Days - Number of Events
timeFrame: From randomization of the first participant to the first opioid use for ≥7 consecutive days up to 25 OCT 2021 cut-off date approximately 59 months
measure: Time to Initiation of Opioid Use for ≥7 Consecutive Days - Month
timeFrame: From randomization of the first participant to the first opioid use for ≥7 consecutive days up to 25 OCT 2021 cut-off date approximately 59 months
Other outcomes:
Locations:
city: Chandler
country: United States
state: Arizona
city: Tucson
country: United States
state: Arizona
city: Beverly Hills
country: United States
state: California
city: Duarte
country: United States
state: California
city: Los Angeles
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state: California
city: Stanford
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state: California
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state: District of Columbia
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state: New Hampshire
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state: Gyeonggido
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state: Seoul Teugbyeolsi
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state: Seoul Teugbyeolsi
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city: Seoul
country: Korea, Republic of
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country: Korea, Republic of
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city: Seoul
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city: Ciudad de Mexico
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state: Distrito Federal
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state: Distrito Federal
city: Cuernavaca
country: Mexico
state: Morelos
city: Monterrey
country: Mexico
state: Nuevo Leon
city: Santiago de Querétaro
country: Mexico
state: Querétaro
city: Mazatlán
country: Mexico
state: Sinaloa
city: Amsterdam
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city: Amsterdam
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city: Den Haag
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city: Dordrecht
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city: Geleen
country: Netherlands
city: Hilversum
country: Netherlands
city: Hoofddorp
country: Netherlands
city: Tilburg
country: Netherlands
city: Lodz
country: Poland
city: Lublin
country: Poland
city: Rybnik
country: Poland
city: Siedlce
country: Poland
city: Waliszew
country: Poland
city: Warszawa
country: Poland
city: Barnaul
country: Russian Federation
city: Chelyabinsk
country: Russian Federation
city: Chelyabinsk
country: Russian Federation
city: Moscow
country: Russian Federation
city: Moscow
country: Russian Federation
city: Novosibirsk
country: Russian Federation
city: Omsk
country: Russian Federation
city: St. Petersburg
country: Russian Federation
city: St. Petersburg
country: Russian Federation
city: St. Petersburg
country: Russian Federation
city: Sabadell
country: Spain
state: Barcelona
city: Palma De Mallorca
country: Spain
state: Illes Baleares
city: Malaga
country: Spain
state: Málaga
city: Barcelona
country: Spain
city: Barcelona
country: Spain
city: Barcelona
country: Spain
city: Barcelona
country: Spain
city: Cáceres
country: Spain
city: Córdoba
country: Spain
city: Lugo
country: Spain
city: Madrid
country: Spain
city: Madrid
country: Spain
city: Valencia
country: Spain
city: Göteborg
country: Sweden
city: Lund
country: Sweden
city: Stockholm
country: Sweden
city: Umea
country: Sweden
city: Uppsala
country: Sweden
city: Kaohsiung City
country: Taiwan
state: Kaohsiung
city: Taichung
country: Taiwan
city: Taipei
country: Taiwan
city: Taipei
country: Taiwan
city: Taoyuan
country: Taiwan
city: Colchester
country: United Kingdom
state: Essex
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country: United Kingdom
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country: United Kingdom
state: North Yorkshire
city: Belfast
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city: Glasgow
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city: London
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city: London
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city: London
country: United Kingdom
Study officials:
affiliation: Bayer
name: Bayer Study Director
role: STUDY_DIRECTOR
References:
citation: Smith MR, Hussain M, Saad F, Fizazi K, Sternberg CN, Crawford D, Manarite J, Muslin D, Farrington T, Tombal B. Darolutamide and survival in metastatic, hormone-sensitive prostate cancer: a patient and caregiver perspective and plain language summary of the ARASENS trial. Future Oncol. 2022 Jul;18(21):2585-2597. doi: 10.2217/fon-2022-0433. Epub 2022 Jun 3.
citation: Smith MR, Hussain M, Saad F, Fizazi K, Sternberg CN, Crawford ED, Kopyltsov E, Park CH, Alekseev B, Montesa-Pino A, Ye D, Parnis F, Cruz F, Tammela TLJ, Suzuki H, Utriainen T, Fu C, Uemura M, Mendez-Vidal MJ, Maughan BL, Joensuu H, Thiele S, Li R, Kuss I, Tombal B; ARASENS Trial Investigators. Darolutamide and Survival in Metastatic, Hormone-Sensitive Prostate Cancer. N Engl J Med. 2022 Mar 24;386(12):1132-1142. doi: 10.1056/NEJMoa2119115. Epub 2022 Feb 17.