Clinical trial NCT02489318: A Study of Apalutamide (JNJ-56021927, ARN-509) Plus Androgen Deprivation Therapy (ADT) Versus ADT in Participants With mHSPC
Official title: A Phase 3 Randomized, Placebo-controlled, Double-blind Study of Apalutamide Plus Androgen Deprivation Therapy (ADT) Versus ADT in Subjects With Metastatic Hormone-sensitive Prostate Cancer (mHSPC)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Prostate Cancer
Keywords: Prostate Cancer
JNJ-56021927
Androgen Deprivation Therapy
ARN-509
Apalutamide
TITAN
Metastatic Hormone-sensitive Prostate Cancer
Lead sponsor: Aragon Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2015-07-03
Enrollment: 1052
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 the addition of apalutamide to ADT provides superior efficacy in improving radiographic progression-free survival (rPFS) or overall survival (OS) for participants with mHSPC.

Detailed description: This is a randomized (study medication assigned to participants by chance), double-blind (neither the researchers nor the participants know what treatment the participant is receiving), placebo-controlled, multinational, multicenter study of apalutamide in participants with mHSPC. The study consists of 4 Phases: Screening Phase (up to 28 days before randomization), Treatment Phase (28 day treatment cycles until disease progression or the occurrence of unacceptable treatment related toxicity), an End of Treatment Phase (until 30 days after the last dose of study drug), and then a Survival Follow up Phase. In the event of a positive study result and notification of unblinding at either of the interim analyses or at the final analysis, participants in the treatment Phase will have the opportunity to enroll in an Open-label Extension Phase, which will allow participants to receive active drug (apalutamide) for approximately 3 years. Participants who are receiving apalutamide in the Open-label Extension Phase may continue receiving apalutamide in the Long-term Extension (LTE) Phase if they will continue to derive benefit from treatment (based on investigator assessment). Participants' safety will be monitored throughout the study.

Eligibility criteria: Inclusion Criteria:

* Diagnosis of prostate adenocarcinoma as confirmed by the investigator
* Metastatic disease documented by greater than or equal to (\>=) 1 bone lesions on 99mTc bone scan. Participants with a single bone lesion must have confirmation of bone metastasis by computed tomography (CT) or magnetic resonance imaging (MRI)
* Eastern Cooperative Oncology Group Performance Status (ECOG PS) grade of 0 or 1
* Participants who received docetaxel treatment must meet the following criteria: a) Received a maximum of 6 cycles of docetaxel therapy for mHSPC; b) Received the last dose of docetaxel \<=2 months prior to randomization; c) Maintained a response to docetaxel of stable disease or better, by investigator assessment of imaging and PSA, prior to randomization
* Other allowed prior treatment for mHSPC: a) Maximum of 1 course of radiation or surgical intervention; radiation therapy for metastatic lesions must be completed prior to randomization; b) Less than or equal to (\<=) 6 months of ADT prior to randomization
* Allowed prior treatments for localized prostate cancer (all treatments must have been completed \>= 1 year prior to randomization) a) \<= 3 years total of ADT; b) All other forms of prior therapies including radiation therapy, prostatectomy,lymph node dissection, and systemic therapies

Exclusion Criteria:

* Pathological finding consistent with small cell, ductal or neuroendocrine carcinoma of the prostate
* Known brain metastases
* Lymph nodes as only sites of metastases
* Visceral (ie, liver or lung) metastases as only sites of metastases
* Other prior malignancy less than or equal to 5 years prior to randomization with the exception of squamous or basal cell skin carcinoma or non-invasive superficial bladder cancer
* Prior treatment with other next generation anti-androgens or other CYP17 inhibitors, immunotherapy or radiopharmaceutical agents for prostate cancer
* History of seizures or medications known to lower seizure threshold

Primary outcomes:
measure: Radiographic Progression-free Survival (rPFS)
timeFrame: Up to 35 months
measure: Overall Survival (OS)
timeFrame: Up to 57 months
Secondary outcomes:
measure: Time to Initiation of Cytotoxic Chemotherapy
timeFrame: Up to 57 months
measure: Time to Pain Progression
timeFrame: Up to 57 months
measure: Time to Chronic Opioid Use
timeFrame: Up to 57 months
measure: Time to Skeletal-related Event (SRE)
timeFrame: Up to 57 months
Other outcomes:
Locations:
city: Homewood
country: United States
state: Alabama
city: Tucson
country: United States
state: Arizona
city: San Bernardino
country: United States
state: California
city: San Diego
country: United States
state: California
city: Denver
country: United States
state: Colorado
city: Norwalk
country: United States
state: Connecticut
city: Fort Myers
country: United States
state: Florida
city: Chicago
country: United States
state: Illinois
city: Fort Wayne
country: United States
state: Indiana
city: Jeffersonville
country: United States
state: Indiana
city: New Orleans
country: United States
state: Louisiana
city: Baltimore
country: United States
state: Maryland
city: Rockville
country: United States
state: Maryland
city: Lansing
country: United States
state: Michigan
city: Troy
country: United States
state: Michigan
city: Omaha
country: United States
state: Nebraska
city: Las Vegas
country: United States
state: Nevada
city: Bronx
country: United States
state: New York
city: Brooklyn
country: United States
state: New York
city: Poughkeepsie
country: United States
state: New York
city: Syracuse
country: United States
state: New York
city: Raleigh
country: United States
state: North Carolina
city: Salisbury
country: United States
state: North Carolina
city: Cleveland
country: United States
state: Ohio
city: Middleburg Heights
country: United States
state: Ohio
city: Springfield
country: United States
state: Oregon
city: Bala-Cynwyd
country: United States
state: Pennsylvania
city: Bryn Mawr
country: United States
state: Pennsylvania
city: Lancaster
country: United States
state: Pennsylvania
city: Charleston
country: United States
state: South Carolina
city: Nashville
country: United States
state: Tennessee
city: Dallas
country: United States
state: Texas
city: Houston
country: United States
state: Texas
city: San Antonio
country: United States
state: Texas
city: Salt Lake City
country: United States
state: Utah
city: Richmond
country: United States
state: Virginia
city: Virginia Beach
country: United States
state: Virginia
city: Burien
country: United States
state: Washington
city: Spokane
country: United States
state: Washington
city: Milwaukee
country: United States
state: Wisconsin
city: Berazategui
country: Argentina
city: C.a.b.a.
country: Argentina
city: Capital Federal
country: Argentina
city: Ciudad Automoma Buenos Aires
country: Argentina
city: Ciudad Autonoma de Buenos Aires
country: Argentina
city: Ciudad De Buenos Aires
country: Argentina
city: Cordoba
country: Argentina
city: La Plata
country: Argentina
city: Pergamino
country: Argentina
city: Rosario
country: Argentina
city: San Miguel de Tucuman
country: Argentina
city: San Salvador de Jujuy
country: Argentina
city: Albury
country: Australia
city: Elizabeth Vale
country: Australia
city: Kogarah
country: Australia
city: Port Macquarie
country: Australia
city: South Brisbane
country: Australia
city: St Leonards
country: Australia
city: Barretos
country: Brazil
city: Florianopolis
country: Brazil
city: Goiania
country: Brazil
city: Ijui
country: Brazil
city: Natal
country: Brazil
city: Ribeirao Preto
country: Brazil
city: Rio de Janeiro
country: Brazil
city: Salvador
country: Brazil
city: Santo Andre
country: Brazil
city: Sao Paulo
country: Brazil
city: Sorocaba
country: Brazil
city: São Paulo
country: Brazil
city: Calgary
country: Canada
state: Alberta
city: Vancouver
country: Canada
state: British Columbia
city: Hamilton
country: Canada
state: Ontario
city: Kingston
country: Canada
state: Ontario
city: Toronto
country: Canada
state: Ontario
city: Quebec
country: Canada
city: Beijing
country: China
city: ChengDu
country: China
city: ChongQing
country: China
city: Fuzhou
country: China
city: Guangzhou
country: China
city: Hangzhou
country: China
city: Nanjing
country: China
city: Shanghai
country: China
city: Suzhou
country: China
city: WuHan
country: China
city: Wuxi
country: China
city: Xi'An
country: China
city: Hradec Králove
country: Czechia
city: Liberec
country: Czechia
city: Nový Jicin
country: Czechia
city: Olomouc
country: Czechia
city: Opava
country: Czechia
city: Pardubice
country: Czechia
city: Praha 10
country: Czechia
city: Praha 2
country: Czechia
city: Praha 4
country: Czechia
city: Praha 5
country: Czechia
city: Praha 8
country: Czechia
city: Zlin
country: Czechia
city: Clermont Ferrand
country: France
city: Montpellier
country: France
city: Nancy
country: France
city: Paris
country: France
city: Pierre Bénite
country: France
city: Strasbourg
country: France
city: Suresnes
country: France
city: Bonn
country: Germany
city: Braunschweig
country: Germany
city: Hamburg
country: Germany
city: Hannover
country: Germany
city: Leipzig
country: Germany
city: Lubeck
country: Germany
city: Lutherstadt Eisleben
country: Germany
city: Nürtingen
country: Germany
city: Sindelfingen
country: Germany
city: Straubing
country: Germany
city: Budapest
country: Hungary
city: Győr
country: Hungary
city: Pécs
country: Hungary
city: Sopron
country: Hungary
city: Beer Sheva
country: Israel
city: Haifa
country: Israel
city: Holon
country: Israel
city: Kfar Saba
country: Israel
city: Petach Tikva
country: Israel
city: Ramat Gan
country: Israel
city: Zrifin
country: Israel
city: Chuo-ku
country: Japan
city: Hakata-Ku
country: Japan
city: Koshigaya
country: Japan
city: Matsuyama
country: Japan
city: Minami-Ku
country: Japan
city: Miyazaki
country: Japan
city: Nagano-shi
country: Japan
city: Nagasaki-shi
country: Japan
city: Osaka City
country: Japan
city: Osaka Sayama shi
country: Japan
city: Sakura
country: Japan
city: Sapporo
country: Japan
city: Yokohama
country: Japan
city: Yufu
country: Japan
city: Daegu
country: Korea, Republic of
city: Daejeon
country: Korea, Republic of
city: Goyang-Si
country: Korea, Republic of
city: Jeollanam-do
country: Korea, Republic of
city: Seongnam-si
country: Korea, Republic of
city: Seoul
country: Korea, Republic of
city: Ciudad de México
country: Mexico
city: Durango
country: Mexico
city: Guadalajara
country: Mexico
city: Leon
country: Mexico
city: Mexico City
country: Mexico
city: Mexico
country: Mexico
city: Morelia
country: Mexico
city: Zapopan
country: Mexico
city: Bialystok
country: Poland
city: Bydgoszcz
country: Poland
city: Krakow
country: Poland
city: Kutno
country: Poland
city: Lodz
country: Poland
city: Lublin
country: Poland
city: Siedlce
country: Poland
city: Sochaczew
country: Poland
city: Warszawa
country: Poland
city: Wroclaw
country: Poland
city: Bucharest
country: Romania
city: Cluj Napoca
country: Romania
city: Craiova
country: Romania
city: Targu Mures
country: Romania
city: Barnaul
country: Russian Federation
city: Ivanovo
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: Pyatigorsk
country: Russian Federation
city: Rostov-on-Don
country: Russian Federation
city: Ryazan
country: Russian Federation
city: Saint-Petersburg
country: Russian Federation
city: Saransk
country: Russian Federation
city: Sochi
country: Russian Federation
city: St Petersburg
country: Russian Federation
city: Tambov
country: Russian Federation
city: Tomsk
country: Russian Federation
city: Tyumen
country: Russian Federation
city: Ufa
country: Russian Federation
city: Vologda
country: Russian Federation
city: Barcelona
country: Spain
city: Cordoba
country: Spain
city: Jerez de la Frontera
country: Spain
city: Madrid
country: Spain
city: Pamplona
country: Spain
city: Göteborg
country: Sweden
city: Malmö
country: Sweden
city: Stockholm
country: Sweden
city: Umeå
country: Sweden
city: Uppsala
country: Sweden
city: Växjö
country: Sweden
city: Örebro
country: Sweden
city: Ankara
country: Turkey
city: Edirne
country: Turkey
city: Istanbul
country: Turkey
city: Izmir
country: Turkey
city: Mersin
country: Turkey
city: Cherkasy
country: Ukraine
city: Dnipo
country: Ukraine
city: Dnipro
country: Ukraine
city: Ivano-Frankivsk
country: Ukraine
city: Khakhiv
country: Ukraine
city: Kharkiv
country: Ukraine
city: Khmelnytsky
country: Ukraine
city: Kyiv
country: Ukraine
city: Lviv
country: Ukraine
city: Odesa
country: Ukraine
city: Poltava
country: Ukraine
city: Uzhgorod
country: Ukraine
city: Vinnitsa
country: Ukraine
city: Zaporizhzhya
country: Ukraine
city: Carlisle
country: United Kingdom
city: Dundee
country: United Kingdom
city: Glasgow
country: United Kingdom
city: London
country: United Kingdom
city: Newcastle Upon Tyne
country: United Kingdom
city: Oxford
country: United Kingdom
city: Plymouth
country: United Kingdom
city: Scunthorpe
country: United Kingdom
city: Stockton on Tees
country: United Kingdom
city: Wolverhampton
country: United Kingdom
Study officials:
affiliation: Janssen Research & Development, LLC
name: Janssen Research & Development, LLC Clinical Trial
role: STUDY_DIRECTOR
References:
citation: Agarwal N, McQuarrie K, Bjartell A, Chowdhury S, Pereira de Santana Gomes AJ, Chung BH, Ozguroglu M, Juarez Soto A, Merseburger AS, Uemura H, Ye D, Given R, Basch E, Miladinovic B, Lopez-Gitlitz A, Chi KN. Apalutamide plus Androgen Deprivation Therapy for Metastatic Castration-Sensitive Prostate Cancer: Analysis of Pain and Fatigue in the Phase 3 TITAN Study. J Urol. 2021 Oct;206(4):914-923. doi: 10.1097/JU.0000000000001841. Epub 2021 May 27.
citation: Chi KN, Chowdhury S, Bjartell A, Chung BH, Pereira de Santana Gomes AJ, Given R, Juarez A, Merseburger AS, Ozguroglu M, Uemura H, Ye D, Brookman-May S, Mundle SD, McCarthy SA, Larsen JS, Sun W, Bevans KB, Zhang K, Bandyopadhyay N, Agarwal N. Apalutamide in Patients With Metastatic Castration-Sensitive Prostate Cancer: Final Survival Analysis of the Randomized, Double-Blind, Phase III TITAN Study. J Clin Oncol. 2021 Jul 10;39(20):2294-2303. doi: 10.1200/JCO.20.03488. Epub 2021 Apr 29.
citation: Uemura H, Koroki Y, Iwaki Y, Imanaka K, Kambara T, Lopez-Gitlitz A, Smith A, Uemura H. Skin rash following Administration of Apalutamide in Japanese patients with Advanced Prostate Cancer: an integrated analysis of the phase 3 SPARTAN and TITAN studies and a phase 1 open-label study. BMC Urol. 2020 Sep 2;20(1):139. doi: 10.1186/s12894-020-00689-0.
citation: Agarwal N, McQuarrie K, Bjartell A, Chowdhury S, Pereira de Santana Gomes AJ, Chung BH, Ozguroglu M, Juarez Soto A, Merseburger AS, Uemura H, Ye D, Given R, Cella D, Basch E, Miladinovic B, Dearden L, Deprince K, Naini V, Lopez-Gitlitz A, Chi KN; TITAN investigators. Health-related quality of life after apalutamide treatment in patients with metastatic castration-sensitive prostate cancer (TITAN): a randomised, placebo-controlled, phase 3 study. Lancet Oncol. 2019 Nov;20(11):1518-1530. doi: 10.1016/S1470-2045(19)30620-5. Epub 2019 Sep 29.
citation: Chi KN, Agarwal N, Bjartell A, Chung BH, Pereira de Santana Gomes AJ, Given R, Juarez Soto A, Merseburger AS, Ozguroglu M, Uemura H, Ye D, Deprince K, Naini V, Li J, Cheng S, Yu MK, Zhang K, Larsen JS, McCarthy S, Chowdhury S; TITAN Investigators. Apalutamide for Metastatic, Castration-Sensitive Prostate Cancer. N Engl J Med. 2019 Jul 4;381(1):13-24. doi: 10.1056/NEJMoa1903307. Epub 2019 May 31.