Clinical trial NCT00638690: Abiraterone Acetate in Castration-Resistant Prostate Cancer Previously Treated With Docetaxel-Based Chemotherapy
Official title: A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study of Abiraterone Acetate (CB7630) Plus Prednisone in Patients With Metastatic Castration-Resistant Prostate Cancer Who Have Failed Docetaxel-Based Chemotherapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Prostatic Neoplasms
Keywords: Metastatic Castration-Resistant Prostate Cancer
CRPC
Abiraterone Acetate
CB7630
Lead sponsor: Cougar Biotechnology, Inc.
Sponsor class: INDUSTRY
First posted: 2008-03-19
Enrollment: 1195
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 patients with metastatic castration-resistant prostate cancer (CRPC) who have failed one or two chemotherapy regimens. At least one of the previous chemotherapies must have contained docetaxel.

Detailed description: Abiraterone acetate is a steroidal irreversible inhibitor of CYP17 (17α hydroxylase/C17, 20-lyase), blocking 2 important enzymatic activities in the synthesis of testosterone. The goal of this study is to compare the clinical benefit of abiraterone acetate plus prednisone with placebo plus prednisone in patients with metastatic castration-resistant prostate cancer (CRPC) who have failed one or two chemotherapy regimens, one of which contains docetaxel. All patients involved in the study will be randomized (assigned by chance) into one of two arms and will not know what study drug is being given to them. Study drug randomization allocation will be 2:1 (abiraterone acetate: placebo). The study will be conducted in the United States, Canada, Australia, and the EU. The study will consist of screening, treatment, and follow-up. In this study, patients will receive study treatment (abiraterone acetate or placebo) plus prednisone until progression of clinical disease. Follow-up will continue until patient dies, is lost to follow-up, or withdraws informed consent. After providing written informed consent, patients will have screening procedures completed to determine eligibility. Safety evaluations at the screening procedure will include a physical examination, vital signs, and clinical blood laboratory tests, ECG, radiographs, urine tests, and recording of any adverse events including details of current prostate cancer symptoms. Patients will be asked to use a method of birth control with adequate barrier protection as determined to be acceptable by the principal investigator and sponsor during the study and for 13 weeks after last study drug administration.

Study medication, abiraterone acetate,is an oral (by mouth) medication to be administered as four (4) 250mg abiraterone acetate tablets or 4 placebo tablets to be taken at least one hour before or two hours after a meal anytime up to 10PM everyday. Prednisone will be administered as 5mg orally twice a day for both groups. Each cycle will be 28 days. Study treatment will continue until disease progression as determined by investigator or when the patient meets criteria for withdrawal from study.

Eligibility criteria: Inclusion Criteria:

* Metastatic Castration-Resistant Prostate Cancer Progression after one or two prior cytotoxic chemotherapies
* At least one chemotherapy must have contained docetaxel
* Eastern Cooperative Oncology Group (ECOG) Performance Status \<= 2
* Medical or surgical castration with testosterone \< 50 ng/dL
* Adequate bone marrow, hepatic and renal function
* Potassium \>= 3.5 mmol/L
* Able to swallow the study drug whole as a tablet
* Informed Consent

Exclusion Criteria:

* More than two prior cytotoxic chemotherapy regimens
* Prior Ketoconazole for prostate cancer
* Prior abiraterone acetate or other CYP17 inhibitor or investigational agents targeting the androgen receptor for prostate cancer
* Uncontrolled hypertension
* Active or symptomatic viral hepatitis or chronic liver disease
* History of pituitary or adrenal dysfunction
* Clinically significant heart disease
* Other malignancy
* Known brain metastasis
* GI disorder affecting absorption
* Not willing to use contraception

Primary outcomes:
measure: Overall Survival
timeFrame: Up to 60 months
Secondary outcomes:
measure: Time to Prostate-Specific Antigen Progression According to Prostate Specific Antigen Working Group Criteria
timeFrame: Up to 12 months
measure: Number of Patients Achieving a Prostate-Specific Antigen Decline >=50%
timeFrame: Up to 12 months
measure: Radiographic Progression-free Survival
timeFrame: Up to 11 months
Other outcomes:
Locations:
city: Birmingham
country: United States
state: Alabama
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
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: Aurora
country: United States
state: Colorado
city: Bristol
country: United States
state: Connecticut
city: New Haven
country: United States
state: Connecticut
city: Stamford
country: United States
state: Connecticut
city: Boca Raton
country: United States
state: Florida
city: Fort Lauderdale
country: United States
state: Florida
city: Fort Myers
country: United States
state: Florida
city: West Palm Beach
country: United States
state: Florida
city: Atlanta
country: United States
state: Georgia
city: Honolulu
country: United States
state: Hawaii
city: Chicago
country: United States
state: Illinois
city: Galesburg
country: United States
state: Illinois
city: Indianapolis
country: United States
state: Indiana
city: Westwood
country: United States
state: Kansas
city: Wichita
country: United States
state: Kansas
city: Marrero
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: Detroit
country: United States
state: Michigan
city: Robbinsdale
country: United States
state: Minnesota
city: St. 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: Box 302
country: United States
state: New York
city: East Setauket
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: Stony Brook
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: Cincinnati
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: 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: Virgiania Beach
country: United States
state: Virginia
city: Seattle
country: United States
state: Washington
city: Adelaide
country: Australia
city: Camperdown
country: Australia
city: Footscray
country: Australia
city: Geelong
country: Australia
city: Heidelberg
country: Australia
city: Herston
country: Australia
city: Hobart
country: Australia
city: Hornsby
country: Australia
city: Kogarah
country: Australia
city: Kurralta Park
country: Australia
city: Liverpool
country: Australia
city: Milton
country: Australia
city: Parkville
country: Australia
city: Perth
country: Australia
city: Subiaco
country: Australia
city: Wodonga
country: Australia
city: Wollongong
country: Australia
city: Linz
country: Austria
city: Salzburg
country: Austria
city: Wien
country: Austria
city: Antwerpen
country: Belgium
city: Bonheiden
country: Belgium
city: Bruxelles
country: Belgium
city: Gent
country: Belgium
city: Hasselt
country: Belgium
city: Kortrijk
country: Belgium
city: Leuven
country: Belgium
city: Liege
country: Belgium
city: Roeselare
country: Belgium
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: Halifax
country: Canada
state: Nova Scotia
city: Hamilton
country: Canada
state: Ontario
city: Toronto
country: Canada
state: Ontario
city: Montreal
country: Canada
state: Quebec
city: Regina
country: Canada
state: Saskatchewan
city: Calgary Ab
country: Canada
city: London
country: Canada
city: Angers Cedex 01
country: France
city: Caen
country: France
city: Cannes
country: France
city: Dijon
country: France
city: Lyon
country: France
city: Paris
country: France
city: Saint Herblain
country: France
city: Vandoeuvre Les Nancy Cedex
country: France
city: Villejuif N/A
country: France
city: Aachen
country: Germany
city: Berlin
country: Germany
city: Dresden
country: Germany
city: Hamburg
country: Germany
city: Homburg/Saar
country: Germany
city: Pecs
country: Hungary
city: Szombathely
country: Hungary
city: Cork
country: Ireland
city: Dublin 7
country: Ireland
city: Dublin
country: Ireland
city: Nijmegen
country: Netherlands
city: Badalona
country: Spain
city: Barcelona
country: Spain
city: Madrid
country: Spain
city: Belfast
country: United Kingdom
city: Birmingham
country: United Kingdom
city: Cambridge
country: United Kingdom
city: Glasgow
country: United Kingdom
city: London
country: United Kingdom
city: Manchester
country: United Kingdom
city: Newcastle Upon Tyne
country: United Kingdom
city: Northwood
country: United Kingdom
city: Oxford
country: United Kingdom
city: Sutton
country: United Kingdom
city: Whitchurch
country: United Kingdom
Study officials:
affiliation: Cougar Biotechnology, Inc.
name: Cougar Biotechnology, Inc Clinical Trial
role: STUDY_DIRECTOR
References:
citation: Heller G, McCormack R, Kheoh T, Molina A, Smith MR, Dreicer R, Saad F, de Wit R, Aftab DT, Hirmand M, Limon A, Fizazi K, Fleisher M, de Bono JS, Scher HI. Circulating Tumor Cell Number as a Response Measure of Prolonged Survival for Metastatic Castration-Resistant Prostate Cancer: A Comparison With Prostate-Specific Antigen Across Five Randomized Phase III Clinical Trials. J Clin Oncol. 2018 Feb 20;36(6):572-580. doi: 10.1200/JCO.2017.75.2998. Epub 2017 Dec 22.
citation: Chi KN, Kheoh T, Ryan CJ, Molina A, Bellmunt J, Vogelzang NJ, Rathkopf DE, Fizazi K, Kantoff PW, Li J, Azad AA, Eigl BJ, Heng DY, Joshua AM, de Bono JS, Scher HI. A prognostic index model for predicting overall survival in patients with metastatic castration-resistant prostate cancer treated with abiraterone acetate after docetaxel. Ann Oncol. 2016 Mar;27(3):454-60. doi: 10.1093/annonc/mdv594. Epub 2015 Dec 18.
citation: Fizazi K, Flaig TW, Stockle M, Scher HI, de Bono JS, Rathkopf DE, Ryan CJ, Kheoh T, Li J, Todd MB, Griffin TW, Molina A, Ohlmann CH. Does Gleason score at initial diagnosis predict efficacy of abiraterone acetate therapy in patients with metastatic castration-resistant prostate cancer? An analysis of abiraterone acetate phase III trials. Ann Oncol. 2016 Apr;27(4):699-705. doi: 10.1093/annonc/mdv545. Epub 2015 Nov 25.
citation: Antoun S, Bayar A, Ileana E, Laplanche A, Fizazi K, di Palma M, Escudier B, Albiges L, Massard C, Loriot Y. High subcutaneous adipose tissue predicts the prognosis in metastatic castration-resistant prostate cancer patients in post chemotherapy setting. Eur J Cancer. 2015 Nov;51(17):2570-7. doi: 10.1016/j.ejca.2015.07.042. Epub 2015 Aug 13.
citation: Xu XS, Ryan CJ, Stuyckens K, Smith MR, Saad F, Griffin TW, Park YC, Yu MK, Vermeulen A, Poggesi I, Nandy P. Correlation between Prostate-Specific Antigen Kinetics and Overall Survival in Abiraterone Acetate-Treated Castration-Resistant Prostate Cancer Patients. Clin Cancer Res. 2015 Jul 15;21(14):3170-7. doi: 10.1158/1078-0432.CCR-14-1549. Epub 2015 Mar 31.
citation: Scher HI, Heller G, Molina A, Attard G, Danila DC, Jia X, Peng W, Sandhu SK, Olmos D, Riisnaes R, McCormack R, Burzykowski T, Kheoh T, Fleisher M, Buyse M, de Bono JS. Circulating tumor cell biomarker panel as an individual-level surrogate for survival in metastatic castration-resistant prostate cancer. J Clin Oncol. 2015 Apr 20;33(12):1348-55. doi: 10.1200/JCO.2014.55.3487. Epub 2015 Mar 23.
citation: Mulders PF, Molina A, Marberger M, Saad F, Higano CS, Chi KN, Li J, Kheoh T, Haqq CM, Fizazi K. Efficacy and safety of abiraterone acetate in an elderly patient subgroup (aged 75 and older) with metastatic castration-resistant prostate cancer after docetaxel-based chemotherapy. Eur Urol. 2014 May;65(5):875-83. doi: 10.1016/j.eururo.2013.09.005. Epub 2013 Sep 20.
citation: Harland S, Staffurth J, Molina A, Hao Y, Gagnon DD, Sternberg CN, Cella D, Fizazi K, Logothetis CJ, Kheoh T, Haqq CM, de Bono JS, Scher HI; COU-AA-301 Investigators. Effect of abiraterone acetate treatment on the quality of life of patients with metastatic castration-resistant prostate cancer after failure of docetaxel chemotherapy. Eur J Cancer. 2013 Nov;49(17):3648-57. doi: 10.1016/j.ejca.2013.07.144. Epub 2013 Aug 22.
citation: Ryan CJ, Molina A, Li J, Kheoh T, Small EJ, Haqq CM, Grant RP, de Bono JS, Scher HI. Serum androgens as prognostic biomarkers in castration-resistant prostate cancer: results from an analysis of a randomized phase III trial. J Clin Oncol. 2013 Aug 1;31(22):2791-8. doi: 10.1200/JCO.2012.45.4595. Epub 2013 Jul 1.
citation: Logothetis CJ, Basch E, Molina A, Fizazi K, North SA, Chi KN, Jones RJ, Goodman OB, Mainwaring PN, Sternberg CN, Efstathiou E, Gagnon DD, Rothman M, Hao Y, Liu CS, Kheoh TS, Haqq CM, Scher HI, de Bono JS. Effect of abiraterone acetate and prednisone compared with placebo and prednisone on pain control and skeletal-related events in patients with metastatic castration-resistant prostate cancer: exploratory analysis of data from the COU-AA-301 randomised trial. Lancet Oncol. 2012 Dec;13(12):1210-7. doi: 10.1016/S1470-2045(12)70473-4. Epub 2012 Nov 9.
citation: Fizazi K, Scher HI, Molina A, Logothetis CJ, Chi KN, Jones RJ, Staffurth JN, North S, Vogelzang NJ, Saad F, Mainwaring P, Harland S, Goodman OB Jr, Sternberg CN, Li JH, Kheoh T, Haqq CM, de Bono JS; COU-AA-301 Investigators. Abiraterone acetate for treatment of metastatic castration-resistant prostate cancer: final overall survival analysis of the COU-AA-301 randomised, double-blind, placebo-controlled phase 3 study. Lancet Oncol. 2012 Oct;13(10):983-92. doi: 10.1016/S1470-2045(12)70379-0. Epub 2012 Sep 18.
citation: de Bono JS, Logothetis CJ, Molina A, Fizazi K, North S, Chu L, Chi KN, Jones RJ, Goodman OB Jr, Saad F, Staffurth JN, Mainwaring P, Harland S, Flaig TW, Hutson TE, Cheng T, Patterson H, Hainsworth JD, Ryan CJ, Sternberg CN, Ellard SL, Flechon A, Saleh M, Scholz M, Efstathiou E, Zivi A, Bianchini D, Loriot Y, Chieffo N, Kheoh T, Haqq CM, Scher HI; COU-AA-301 Investigators. Abiraterone and increased survival in metastatic prostate cancer. N Engl J Med. 2011 May 26;364(21):1995-2005. doi: 10.1056/NEJMoa1014618.