Clinical trial NCT01715285: A Study of Abiraterone Acetate Plus Low-Dose Prednisone Plus Androgen Deprivation Therapy (ADT) Versus ADT Alone in Newly Diagnosed Participants With High-Risk, Metastatic Hormone-Naive Prostate Cancer (mHNPC)
Official title: A Randomized, Double-blind, Comparative Study of Abiraterone Acetate Plus Low-Dose Prednisone Plus Androgen Deprivation Therapy (ADT) Versus ADT Alone in Newly Diagnosed Subjects With High-Risk, Metastatic Hormone-naive Prostate Cancer (mHNPC)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Prostate Neoplasms
Keywords: Prostate neoplasms
Prostate cancer
Metastatic prostate cancer
Abiraterone acetate
ZYTIGA
Prednisone
Androgen deprivation therapy
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
First posted: 2012-10-26
Enrollment: 1209
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 determine if newly diagnosed (within previous 3 months) participants with metastatic (spread of cancer cells from one part of the body to another ) hormone-naive prostate cancer (mHNPC) who have high-risk prognostic factors will benefit from the addition of abiraterone acetate plus low-dose prednisone to androgen deprivation therapy (ADT; lutenizing hormone releasing hormone \[LHRH\] agonists or surgical castration).

Detailed description: This is a randomized (the treatment group is assigned by chance), double-blind (neither physician nor participant knows the treatment that the participant receives), placebo (an inactive substance that is compared with a drug to test whether the drug has a real effect in a clinical trial)-controlled study designed to determine the efficacy of abiraterone acetate plus low-dose prednisone in participants with mHNPC. The study consists of 4 parts: Screening Phase (that is, 28 days before study commences on Day 1); Double-blind treatment Phase (consists of 4-week dosing cycles wherein abiraterone acetate will be administered as 1,000 milligram \[mg\] plus 5 mg prednisone or only placebo orally); Follow-up Phase (every 4 months up to 60 months or until death, lost to follow up, withdrawal of consent or study termination) Open-label Extension (OLE) Phase. Participants in the Double-blind Treatment Phase will have the opportunity to enroll into the OLE Phase. The OLE Phase will allow participants to receive active drug (abiraterone acetate plus prednisone) until Long-term Extension (LTE) Phase for an additional period of up to 3 years. Participants will discontinue study treatment at disease progression or unacceptable toxicity unless, in the Investigator's opinion, it is deemed that the participants will continue to derive benefit from study treatment. Participants will be randomized in a 1:1 ratio to the active treatment group (abiraterone acetate 1000 mg daily plus prednisone 5 mg daily plus ADT) or the control group (ADT plus placebos).Efficacy will be evaluated primarily by overall survival and radiographic progression-free survival. Participants' safety will be monitored throughout the study.

Eligibility criteria: Inclusion Criteria:

* Newly diagnosed metastatic prostate cancer within 3 months prior to randomization with histologically or cytologically confirmed adenocarcinoma of the prostate without neuroendocrine differentiation or small cell histology
* Distant metastatic disease documented by positive bone scan or metastatic lesions on computed tomography (CT) or magnetic resonance imaging (MRI) scan
* At least 2 of the following high-risk prognostic factors: Gleason score of greater than or equal to (\>=8); presence of 3 or more lesions on bone scan; presence of measurable visceral (excluding lymph node disease) metastasis on CT or MRI Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 scan
* Eastern Cooperative Oncology Group (ECOG) performance status grade of 0, 1 or 2
* Adequate hematologic, hepatic, and renal function
* Agrees to protocol-defined use of effective contraception

Exclusion Criteria:

* Active infection or other medical condition that would make prednisone use contraindicated
* Any chronic medical condition requiring a higher systemic dose of corticosteroid than 5 mg prednisone per day
* Pathological finding consistent with small cell carcinoma of the prostate
* Known brain metastasis
* Any prior pharmacotherapy, radiation therapy, or surgery for metastatic prostate cancer (the following exception are permitted): up to 3 months of androgen deprivation therapy (ADT) with lutenizing hormone releasing hormone agonists or antagonists or orchiectomy with or without concurrent anti-androgens prior Cycle 1 Day 1; participants may have one course of palliative radiation or surgical therapy to treat symptoms resulting from metastatic disease if it was administered at least 28 days prior to Cycle 1 Day 1)

Primary outcomes:
measure: Radiographic Progression-Free Survival (PFS)
timeFrame: Up to 44 months
measure: Overall Survival (OS)
timeFrame: Up to 66 months
Secondary outcomes:
measure: Time to Initiation of Chemotherapy
timeFrame: Up to 66 months
measure: Time to Subsequent Therapy for Prostate Cancer
timeFrame: Up to 66 months
measure: Time to Pain Progression
timeFrame: Up to 66 months
measure: Time to Skeletal-Related Event
timeFrame: Up to 66 months
measure: Time to Prostate-Specific Antigen (PSA) Progression
timeFrame: Up to 66 months
Other outcomes:
Locations:
city: Buenos Aires
country: Argentina
city: Caba
country: Argentina
city: Cordoba
country: Argentina
city: La Rioja
country: Argentina
city: Rosario
country: Argentina
city: Adelaide
country: Australia
city: Footscray
country: Australia
city: Liverpool
country: Australia
city: Malvern
country: Australia
city: Randwick
country: Australia
city: Wahroonga
country: Australia
city: Antwerpen
country: Belgium
city: Bonheiden
country: Belgium
city: Brasschaat
country: Belgium
city: Bruxelles
country: Belgium
city: Charleroi
country: Belgium
city: Liège
country: Belgium
city: Namur
country: Belgium
city: Ottignies
country: Belgium
city: Sint-Niklaas
country: Belgium
city: Yvoir
country: Belgium
city: Barretos
country: Brazil
city: Belo Horizonte
country: Brazil
city: Caxias Do Sul
country: Brazil
city: Curitiba
country: Brazil
city: Ijui
country: Brazil
city: Jau
country: Brazil
city: Natal
country: Brazil
city: Novo Hamburgo
country: Brazil
city: Porto Alegre
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city: Ribeirao Preto
country: Brazil
city: Rio de Janeiro
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city: Salvador
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city: Sao Jose Do Rio Preto
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city: Sao Paulo
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city: Gabrovo
country: Bulgaria
city: Sofia
country: Bulgaria
city: Edmonton
country: Canada
state: Alberta
city: Vancouver
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state: British Columbia
city: Winnipeg
country: Canada
state: Manitoba
city: Hamilton
country: Canada
state: Ontario
city: Kingston
country: Canada
state: Ontario
city: Oshawa
country: Canada
state: Ontario
city: Ottawa
country: Canada
state: Ontario
city: Toronto
country: Canada
state: Ontario
city: Montreal
country: Canada
state: Quebec
city: Quebec
country: Canada
city: Santiago
country: Chile
city: Beijing
country: China
city: Chengdu
country: China
city: Chongqing
country: China
city: Guangzhou
country: China
city: Hangzhou
country: China
city: Nanjing
country: China
city: Shanghai
country: China
city: Su Zhou
country: China
city: Tianjin
country: China
city: Wuhan
country: China
city: Bogota
country: Colombia
city: Floridablanca
country: Colombia
city: Medellin
country: Colombia
city: Hradec Kralove
country: Czechia
city: Olomouc
country: Czechia
city: Plzen
country: Czechia
city: Praha 10
country: Czechia
city: Praha 2
country: Czechia
city: Praha 4
country: Czechia
city: Aarhus N.
country: Denmark
city: Holsterbro
country: Denmark
city: Odense N/a
country: Denmark
city: Roskilde
country: Denmark
city: Vejle
country: Denmark
city: Oulu
country: Finland
city: Tampere
country: Finland
city: La Chaussee St Victor
country: France
city: Lille
country: France
city: Montpellier
country: France
city: Paris Cedex 14
country: France
city: Suresnes
country: France
city: Toulouse
country: France
city: Villejuif Cedex
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city: Düsseldorf
country: Germany
city: Hamburg
country: Germany
city: Nürtingen
country: Germany
city: Budapest N/a
country: Hungary
city: Budapest
country: Hungary
city: Győr
country: Hungary
city: Miskolc
country: Hungary
city: Pecs
country: Hungary
city: Szentes
country: Hungary
city: Beer Yaakov
country: Israel
city: Beer-Sheva
country: Israel
city: Haifa
country: Israel
city: Jerusalem
country: Israel
city: Kfar Saba
country: Israel
city: Petah-Tikva
country: Israel
city: Ramat Gan
country: Israel
city: Chiba
country: Japan
city: Gifu
country: Japan
city: Kashiwa
country: Japan
city: Matsuyama
country: Japan
city: Nankoku
country: Japan
city: Osaka-Sayama
country: Japan
city: Sakura
country: Japan
city: Tokushima
country: Japan
city: Tokyo
country: Japan
city: Ube
country: Japan
city: Yokohama
country: Japan
city: Yufu
country: Japan
city: Bucheon-Si
country: Korea, Republic of
city: Busan
country: Korea, Republic of
city: Daegu
country: Korea, Republic of
city: Daejeon
country: Korea, Republic of
city: Gyeonggi-do
country: Korea, Republic of
city: Seoul
country: Korea, Republic of
city: Kuala Lumpur
country: Malaysia
city: Kuching
country: Malaysia
city: Chihuahua
country: Mexico
city: Cuernavaca
country: Mexico
city: Durango
country: Mexico
city: Guadalajara
country: Mexico
city: Monterrey
country: Mexico
city: Oaxaca
country: Mexico
city: Pachuca de Soto
country: Mexico
city: Zapopan
country: Mexico
city: Alkmaar
country: Netherlands
city: Amsterdam Zuidoost
country: Netherlands
city: Amsterdam
country: Netherlands
city: Hilversum
country: Netherlands
city: Hoofddorp
country: Netherlands
city: Nieuwegein
country: Netherlands
city: Rotterdam
country: Netherlands
city: Auckland
country: New Zealand
city: Christchurch
country: New Zealand
city: Hamilton
country: New Zealand
city: Tauranga
country: New Zealand
city: Bydgoszcz
country: Poland
city: Gdansk
country: Poland
city: Lodz
country: Poland
city: Lublin
country: Poland
city: Warszawa
country: Poland
city: Braga
country: Portugal
city: Coimbra
country: Portugal
city: Lisboa
country: Portugal
city: Porto
country: Portugal
city: Brasov
country: Romania
city: Bucharest
country: Romania
city: Bucuresti
country: Romania
city: Cluj Napoca
country: Romania
city: Iasi
country: Romania
city: Chelyabinsk
country: Russian Federation
city: Ekaterinburg
country: Russian Federation
city: Ivanovo
country: Russian Federation
city: Izhevsk
country: Russian Federation
city: Moscow
country: Russian Federation
city: Nizhny Novgorod
country: Russian Federation
city: Obninsk
country: Russian Federation
city: Omsk
country: Russian Federation
city: Orenburg
country: Russian Federation
city: Pyatigorsk
country: Russian Federation
city: Rostov-on-Don
country: Russian Federation
city: Ryazan
country: Russian Federation
city: Sankt-Peterburg
country: Russian Federation
city: Saransk
country: Russian Federation
city: Saratov
country: Russian Federation
city: Sochi
country: Russian Federation
city: St.-Petersburg
country: Russian Federation
city: Stavropol
country: Russian Federation
city: Tumen
country: Russian Federation
city: Ufa
country: Russian Federation
city: Volgograd
country: Russian Federation
city: Yoshkar-Ola
country: Russian Federation
city: Košice-Šaca
country: Slovakia
city: Martin
country: Slovakia
city: Piestany
country: Slovakia
city: Prešov
country: Slovakia
city: Rimavska Sobota
country: Slovakia
city: Trnava
country: Slovakia
city: George
country: South Africa
city: Port Elizabeth
country: South Africa
city: Pretoria
country: South Africa
city: Vosloorus
country: South Africa
city: Barcelona
country: Spain
city: Cordoba
country: Spain
city: Coruña
country: Spain
city: Madrid N/a
country: Spain
city: Madrid
country: Spain
city: Murcia N/a
country: Spain
city: Göteborg
country: Sweden
city: Malmö
country: Sweden
city: Stockholm
country: Sweden
city: Umeå
country: Sweden
city: Uppsala
country: Sweden
city: Adana
country: Turkey
city: Ankara
country: Turkey
city: Istanbul
country: Turkey
city: Izmir
country: Turkey
city: Zonguldak
country: Turkey
city: Cherkassy
country: Ukraine
city: Dnepropetrovsk
country: Ukraine
city: Dnipro
country: Ukraine
city: Khakhiv
country: Ukraine
city: Kharkiv
country: Ukraine
city: Kyiv
country: Ukraine
city: Lviv
country: Ukraine
city: Makiivka
country: Ukraine
city: Odessa
country: Ukraine
city: Uzhgorod
country: Ukraine
city: Zaporizhzhia
country: Ukraine
city: Cambridge
country: United Kingdom
city: Glasgow
country: United Kingdom
city: Manchester
country: United Kingdom
city: Nottingham
country: United Kingdom
city: Oxford
country: United Kingdom
city: Plymouth
country: United Kingdom
Study officials:
affiliation: Janssen Research & Development, LLC
name: Janssen Research & Development, LLC Clinical Trial
role: STUDY_DIRECTOR
References:
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