Clinical trial NCT00887198: Abiraterone Acetate in Asymptomatic or Mildly Symptomatic Patients With Metastatic Castration-Resistant Prostate Cancer
Official title: A Phase 3, Randomized, Double-blind, Placebo-Controlled Study of Abiraterone Acetate (CB7630) Plus Prednisone in Asymptomatic or Mildly Symptomatic Patients With Metastatic Castration-Resistant Prostate Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Prostate Cancer
Keywords: Prostate cancer
Abiraterone acetate
CB7630
CRPC
Metastatic castration-resistant prostate cancer
hormone refractory prostate cancer
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
First posted: 2009-04-23
Enrollment: 1088
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: This is a phase 3 study to compare the clinical benefit of abiraterone acetate plus prednisone with placebo plus prednisone in asymptomatic or mildly symptomatic patients with metastatic castration-resistant prostate cancer (CRPC).

Detailed description: This is a randomized (individuals will be assigned by chance to study treatments), double-blind (individuals and study personnel will not know the identity of study treatments), 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 in approximately 1,000 medically or surgically castrated male patients with metastatic CRPC who have shown tumor progression and are asymptomatic or mildly symptomatic. The study period will consist of screening, treatment, and follow-up phases. Patients will receive study treatment (abiraterone acetate or placebo) plus prednisone until radiographic progression of disease and/or unequivocal clinical progression. Efficacy evaluations will be performed throughout the treatment period and safety will be assessed until 30 days after the last dose of abiraterone acetate. throughout the study. Follow-up will continue for up to 60 months (5 years) or until the patient dies, is lost to follow-up, or withdraws informed consent. At the interim analysis of overall survival (OS; 43% of death events), the independent data monitoring committee (IDMC) reviewed the efficacy and safety data and concluded that all of the data pointed to a significant advantage for patients in one arm of the study compared with the other arm thereby unanimously recommending unblinding the study and allowing crossover from the placebo arm to active therapy. Patients currently receiving placebo will be offered crossover therapy to abiraterone acetate. Treatment for patients who were originally randomized to the abiraterone acetate treatment group will not change. Patients will be discontinued from long term follow-up at the time of the Clinical Cut-Off Date for Final Analysis (CCO-FA); however, patients still receiving treatment with abiraterone acetate at the CCO-FA will be offered to receive continued treatment for an additional period of up to 3 years or until disease progression or unacceptable toxicity. For these patients, safety assessment will be performed while continuing treatment, and for 30 days after the last dose of abiraterone acetate.

Eligibility criteria: Inclusion Criteria:

* Metastatic castration-resistant prostate cancer (CRPC)
* Previous anti-androgen therapy and progression after withdrawal
* ECOG performance status of either 0 or 1
* Medical or surgical castration with testosterone less than 50 ng/dL
* Life expectancy of at least 6 months

Exclusion Criteria:

* Prior cytotoxic chemotherapy or biologic therapy for CRPC
* Prior ketoconazole for prostate cancer
* Known brain metastasis or visceral organ metastasis
* Use of opiate analgesics for cancer-related pain, including codeine and dextropropoxyphene, currently or anytime within 4 weeks of Cycle 1 Day 1

Primary outcomes:
measure: Overall Survival
timeFrame: From randomization (Day 1) up to end of study (Month 60)
measure: Radiographic Progression-free Survival (rPFS)
timeFrame: From randomization (Day 1) up to first radiographic progression or cutoff date (Month 18)
Secondary outcomes:
measure: Time to Opiate Use for Prostate Cancer Pain
timeFrame: From randomization (Day 1) up to first opiate use or end of study (Month 60)
measure: Time to Initiation of Cytotoxic Chemotherapy
timeFrame: From randomization (Day 1) up to initiation of cytotoxic chemotherapy or cutoff date (Month 18)
measure: Time to Deterioration in Eastern Cooperative Oncology Group (ECOG) Performance Score by >=1 Point
timeFrame: From randomization (Day 1) up to first radiographic progression or cutoff date (Month 18)
measure: Time to Prostate-specific Antigen (PSA) Progression
timeFrame: From randomization (Day 1) up to date of PSA progerssion or cutoff date (Month 18)
measure: Number of Participants With Treatment Emergent Adverse Events
timeFrame: From first dose of study drug up to 30 days after the last dose of study drug
measure: Mean Plasma Concentrations of Abiraterone
timeFrame: Up to Cycle 5, Day 1
measure: Maximum Plasma Concentrations of Abiraterone
timeFrame: Up to Cycle 5, Day 1
measure: Area Under the Plasma Concentration-time Curve From Time 0 to Time the Last Quantifiable Concentration of Abiraterone (AUC[0-infinity])
timeFrame: Up to Cycle 5, Day 1
measure: Elimination Half-Life (t1/2)
timeFrame: Up to Cycle 5, Day 1
Other outcomes:
Locations:
city: Birmingham
country: United States
state: Alabama
city: Tucson
country: United States
state: Arizona
city: Bellflower
country: United States
state: California
city: Los Angeles
country: United States
state: California
city: Marina Del Rey
country: United States
state: California
city: Sacramento
country: United States
state: California
city: San Diego
country: United States
state: California
city: San Francisco
country: United States
state: California
city: Stanford
country: United States
state: California
city: Aurora
country: United States
state: Colorado
city: New Haven
country: United States
state: Connecticut
city: Boca Raton
country: United States
state: Florida
city: Fort Myers
country: United States
state: Florida
city: Gainesville
country: United States
state: Florida
city: Atlanta
country: United States
state: Georgia
city: Honolulu
country: United States
state: Hawaii
city: Kansas City
country: United States
state: Kansas
city: Metairie
country: United States
state: Louisiana
city: New Orleans
country: United States
state: Louisiana
city: Baltimore
country: United States
state: Maryland
city: Boston
country: United States
state: Massachusetts
city: Dearborn
country: United States
state: Michigan
city: Saint Louis Park
country: United States
state: Minnesota
city: Saint Louis
country: United States
state: Missouri
city: Billings
country: United States
state: Montana
city: Omaha
country: United States
state: Nebraska
city: Las Vegas
country: United States
state: Nevada
city: East Syracuse
country: United States
state: New York
city: New Hyde Park
country: United States
state: New York
city: New York
country: United States
state: New York
city: Syracuse
country: United States
state: New York
city: Durham
country: United States
state: North Carolina
city: Raleigh
country: United States
state: North Carolina
city: Canton
country: United States
state: Ohio
city: Cleveland
country: United States
state: Ohio
city: Portland
country: United States
state: Oregon
city: Philadelphia
country: United States
state: Pennsylvania
city: Pittsburgh
country: United States
state: Pennsylvania
city: Columbia
country: United States
state: South Carolina
city: Myrtle Beach
country: United States
state: South Carolina
city: Chattanooga
country: United States
state: Tennessee
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: Norfolk
country: United States
state: Virginia
city: Seattle
country: United States
state: Washington
city: Madison
country: United States
state: Wisconsin
city: Adelaide
country: Australia
city: Camperdown
country: Australia
city: Footscray
country: Australia
city: Frankston
country: Australia
city: Garran
country: Australia
city: Geelong
country: Australia
city: Heidelberg
country: Australia
city: Herston
country: Australia
city: Hornsby
country: Australia
city: Kogarah
country: Australia
city: Kurralta Park
country: Australia
city: Lismore
country: Australia
city: Liverpool
country: Australia
city: Malvern
country: Australia
city: Parkville
country: Australia
city: Perth
country: Australia
city: South Brisbane
country: Australia
city: Southport
country: Australia
city: Subiaco
country: Australia
city: Aalst
country: Belgium
city: Antwerpen
country: Belgium
city: Gent
country: Belgium
city: Hasselt
country: Belgium
city: Leuven
country: Belgium
city: Roeselare
country: Belgium
city: Calgary
country: Canada
state: Alberta
city: Edmonton
country: Canada
state: Alberta
city: Kelowna
country: Canada
state: British Columbia
city: Vancouver
country: Canada
state: British Columbia
city: Victoria
country: Canada
state: British Columbia
city: Hamilton
country: Canada
state: Ontario
city: London
country: Canada
state: Ontario
city: Toronto
country: Canada
state: Ontario
city: Montreal
country: Canada
state: Quebec
city: Quebec
country: Canada
city: Caen
country: France
city: Clichy
country: France
city: Dijon Cedex
country: France
city: La Roche sur Yon
country: France
city: Lyon Cedex 03
country: France
city: Lyon
country: France
city: Montpellier
country: France
city: Paris Cedex 15
country: France
city: Tours
country: France
city: Villejuif
country: France
city: Aachen
country: Germany
city: Berlin
country: Germany
city: Braunschweig
country: Germany
city: Dresden
country: Germany
city: Düsseldorf
country: Germany
city: Hamburg
country: Germany
city: Hannover
country: Germany
city: Homburg
country: Germany
city: Kempen
country: Germany
city: Leipzig
country: Germany
city: Muenchen
country: Germany
city: Münster
country: Germany
city: Wuppertal
country: Germany
city: Athens
country: Greece
city: Larisa
country: Greece
city: Amsterdam
country: Netherlands
city: Heerlen
country: Netherlands
city: Nijmegen
country: Netherlands
city: Rotterdam
country: Netherlands
city: Barcelona
country: Spain
city: Coruña
country: Spain
city: Hospitalet de Llobregat
country: Spain
city: Madrid
country: Spain
city: Oviedo
country: Spain
city: Santander N/a
country: Spain
city: Santiago De Compostela
country: Spain
city: Göteborg
country: Sweden
city: Malmö N/a
country: Sweden
city: Stockholm
country: Sweden
city: Uppsala
country: Sweden
city: Växjö
country: Sweden
city: Birmingham
country: United Kingdom
city: Cambridge
country: United Kingdom
city: Glasgow
country: United Kingdom
city: Leeds
country: United Kingdom
city: London
country: United Kingdom
city: Manchester
country: United Kingdom
city: Newcastle Upon Tyne
country: United Kingdom
city: Oxford
country: United Kingdom
city: Sutton
country: United Kingdom
city: Whitchurch
country: United Kingdom
city: Wirral
country: United Kingdom
Study officials:
affiliation: Janssen Research & Development, LLC
name: Janssen Research & Development, LLC Clinical Trial
role: STUDY_DIRECTOR
References:
citation: Lorente D, Llacer C, Lozano R, de Velasco G, Romero-Laorden N, Rodrigo M, Sanchez-Iglesias A, di Capua C, Castro E, Ferrer C, Sanchez-Hernandez A, Olmos D. Prognostic Score and Benefit from Abiraterone in First-line Metastatic, Castration-resistant Prostate Cancer. Eur Urol. 2021 Nov;80(5):641-649. doi: 10.1016/j.eururo.2021.07.014. Epub 2021 Aug 6.
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citation: Ryan CJ, Smith MR, de Bono JS, Molina A, Logothetis CJ, de Souza P, Fizazi K, Mainwaring P, Piulats JM, Ng S, Carles J, Mulders PF, Basch E, Small EJ, Saad F, Schrijvers D, Van Poppel H, Mukherjee SD, Suttmann H, Gerritsen WR, Flaig TW, George DJ, Yu EY, Efstathiou E, Pantuck A, Winquist E, Higano CS, Taplin ME, Park Y, Kheoh T, Griffin T, Scher HI, Rathkopf DE; COU-AA-302 Investigators. Abiraterone in metastatic prostate cancer without previous chemotherapy. N Engl J Med. 2013 Jan 10;368(2):138-48. doi: 10.1056/NEJMoa1209096. Epub 2012 Dec 10.