Safety Study of Continued Enzalutamide Treatment In Prostate Cancer Patients
- Conditions
- Prostate Cancer
- Interventions
- Registration Number
- NCT01995513
- Lead Sponsor
- Pfizer
- Brief Summary
The purpose of this study is to determine if continued treatment with Enzalutamide is effective in patients with metastatic prostate cancer.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Male
- Target Recruitment
- 509
- Men with metastatic castration-resistant prostate cancer
- Progressive disease on androgen deprivation therapy
- Patients must agree to continue androgen deprivation therapy with a GnRH agonist/antagonist throughout the study or have had a prior bilateral orchiectomy
- ECOG performance score ≤ 1
- Estimated life expectancy of ≥ 12 months
- Prior cytotoxic chemotherapy, aminoglutethimide, ketoconazole, abiraterone, or enzalutamide for the treatment of prostate cancer
- Prior participation in a clinical trial of an investigational agent that inhibits the androgen receptor or androgen synthesis (unless the treatment was placebo)
- History of brain metastasis, active leptomeningeal disease or seizure
- Severe cardiovascular or hepatic disease
- Pituitary or adrenal dysfunction
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Enzalutamide & Abiraterone/prednisone Prednisone Enzalutamide (160 mg) administered as four 40-mg capsules by mouth once daily in combination with abiraterone (1000 mg) administered as four 250-mg tablets by mouth once daily and prednisone (10 mg) administered as one 5-mg tablet by mouth twice daily Enzalutamide placebo & Abiraterone/prednisone Placebo for Enzalutamide Enzalutamide placebo (placebo) capsules (identical in appearance to enzalutamide) administered as 4 capsules by mouth once daily in combination with abiraterone (1000 mg) administered as four 250-mg tablets by mouth once daily and prednisone (10 mg) administered as one 5-mg tablet by mouth twice daily. Enzalutamide & Abiraterone/prednisone Enzalutamide Enzalutamide (160 mg) administered as four 40-mg capsules by mouth once daily in combination with abiraterone (1000 mg) administered as four 250-mg tablets by mouth once daily and prednisone (10 mg) administered as one 5-mg tablet by mouth twice daily Enzalutamide & Abiraterone/prednisone Abiraterone Enzalutamide (160 mg) administered as four 40-mg capsules by mouth once daily in combination with abiraterone (1000 mg) administered as four 250-mg tablets by mouth once daily and prednisone (10 mg) administered as one 5-mg tablet by mouth twice daily Enzalutamide placebo & Abiraterone/prednisone Abiraterone Enzalutamide placebo (placebo) capsules (identical in appearance to enzalutamide) administered as 4 capsules by mouth once daily in combination with abiraterone (1000 mg) administered as four 250-mg tablets by mouth once daily and prednisone (10 mg) administered as one 5-mg tablet by mouth twice daily. Enzalutamide placebo & Abiraterone/prednisone Prednisone Enzalutamide placebo (placebo) capsules (identical in appearance to enzalutamide) administered as 4 capsules by mouth once daily in combination with abiraterone (1000 mg) administered as four 250-mg tablets by mouth once daily and prednisone (10 mg) administered as one 5-mg tablet by mouth twice daily.
- Primary Outcome Measures
Name Time Method Progression Free Survival (PFS) From randomization until disease progression, last tumor assessment without disease progression or death due to any cause, whichever occurred first (maximum up to 20.3 months) PFS = time from randomization to first documentation of radiographic progression (RP),unequivocal clinical progression or death due to any cause (death within 112 days of treatment discontinuation without objective evidence of RP),whichever occurred first as per investigator. Unequivocal disease progression was pain requiring chronic administration of analgesics, decline of prostate cancer of Eastern Cooperative Oncology Group (ECOG) performance status score to 3 or higher or initiation of new anticancer therapy/radiation therapy or surgical intervention due to tumor progression. ECOG score range= 0(no severity) to 5(maximum severity).RP for bone disease was evaluated by appearance of 2 or more new bone lesions as per Prostate Cancer Clinical Trials Working Group 2 (PCWG2) or for soft tissue disease according to Response Evaluation Criteria in Solid Tumor version 1.1. Participants with no PFS event at analysis date were censored at last tumor assessment date prior to data cutoff date.
- Secondary Outcome Measures
Name Time Method Change From Baseline in Quality of Life as Assessed by Functional Assessment of Cancer Therapy-Prostate (FACT-P) Physical Well-Being Domain Scores Baseline, Week 9, 13, 17, 21, 25, 29, 33, 37, 41, 45, 49, 53, 57, 61, 65, 69, 73, 77, 81, 85, 89 The FACT-P is a multidimensional, self-reported quality of life instrument consisting of 27 core items that assess participant function in 4 domains: physical, social/family, emotional, functional well-being, and supplemented by 12 site-specific items to assess for prostate-related symptoms. Each item is rated on a 0 to 4 Likert-type scale, and then combined to produce subscale scores for each domain. Total subscale score range for physical well-being domain is from 0 (worst response) to 28 (best response), where higher score indicate better quality of life.
Prostate Specific Antigen (PSA) Response Rate From randomization until disease progression, last tumor assessment without disease progression, whichever occurred first (maximum up to 11.1 months) PSA response rate was defined as percentage of participants with \>=30% and \>=50% decrease in PSA from baseline at randomization to the maximal PSA response with a threshold of 30% and 50% respectively. PSA response was confirmed if another assessment measured at least 3 weeks later met the criterion as well.
Objective Response Rate (ORR) From randomization until CR or PR, whichever occurred first (maximum up to 21.3 months) Objective response rate as assessed by the investigator according to Response Evaluation Criteria in Solid Tumor version 1.1 (RECIST v1.1) was defined as 1) Percentage of participants with confirmed best overall complete response (CR) and partial response (PR); 2) Percentage of participants with CR, PR and stable disease (SD) for target lesions or non-progressive disease for non-target lesions. CR: Disappearance of all non-nodal target and non-target lesions, including target and non-target lymph nodes reduction to \<10 millimeter (mm) in short axis. No new lesions and disappearance of all non-target lesions. PR: \>= 30% decrease in sum of diameters of target lesions, compared to the sum at baseline. The short axis was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions.
Rate of Pain Progression Month 6 Rate of pain progression was defined as percentage of participants with an increase of \>=30% from baseline in the mean Brief Pain Inventory-Short Form (BPI-SF) pain intensity item scores of 4 items assessing average, worst, least, and intermediate pain severity. BPI-SF is an 11-item self-report questionnaire that is designed to assess the severity and impact of pain on daily functions of a participant. BPI-sf includes 4 questions that assess pain intensity (worst, least, average, right now) and 7 questions that assess impact of pain on daily functions (general activity, mood, walking ability, normal work, relations with other people, sleep, enjoyment of life). BPI-sf score range for each item was from 0=no pain to 10=worst possible pain. Total score was reported as average of individual questions ranges from 0 to 10, where lower scores indicated less pain or less pain interference.
Change From Baseline in Quality of Life as Assessed by Functional Assessment of Cancer Therapy-Prostate (FACT-P) Social/Family Well-Being Domain Scores Baseline, Week 9, 13, 17, 21, 25, 29, 33, 37, 41, 45, 49, 53, 57, 61, 65, 69, 73, 77, 81, 85, 89 The FACT-P is a multidimensional, self-reported quality of life instrument consisting of 27 core items that assess participant function in 4 domains: physical, social/family, emotional, functional well-being, and supplemented by 12 site-specific items to assess for prostate-related symptoms. Each item is rated on a 0 to 4 Likert-type scale, and then combined to produce subscale scores for each domain. Total subscale score range for social/family well-being domain is from 0 (worst response) to 32 (best response), where higher score indicate better quality of life.
Change From Baseline in Quality of Life as Assessed by Functional Assessment of Cancer Therapy-Prostate (FACT-P) Global Score Baseline, Week 9, 13, 17, 21, 25, 29, 33, 37, 41, 45, 49, 53, 57, 61, 65, 69, 73, 77, 81, 85, 89 The FACT-P is a multidimensional, self-reported quality of life instrument consisting of 27 core items that assess participant function in 4 domains: physical, social/family, emotional, functional well-being, and supplemented by 12 site-specific items to assess for prostate-related symptoms. Each item is rated on a 0 to 4 Likert-type scale, and then combined to produce subscale scores for each domain, as well as a global quality of life score which is the sum of all 5 domain scores and ranges from 0 to 156 where higher scores represent better quality of life.
Change From Baseline in Quality of Life as Assessed by Functional Assessment of Cancer Therapy-Prostate (FACT-P) Emotional Well-Being Domain Scores Baseline, Week 9, 13, 17, 21, 25, 29, 33, 37, 41, 45, 49, 53, 57, 61, 65, 69, 73, 77, 81, 85, 89 The FACT-P is a multidimensional, self-reported quality of life instrument consisting of 27 core items that assess participant function in 4 domains: physical, social/family, emotional, functional well-being, and supplemented by 12 site-specific items to assess for prostate-related symptoms. Each item is rated on a 0 to 4 Likert-type scale, and then combined to produce subscale scores for each domain. Total subscale score range for emotional well-being domain is from 0 (worst response) to 24 (best response), where higher score indicate better quality of life.
Time to Prostate Specific Antigen (PSA) Progression From randomization until disease progression, last tumor assessment without disease progression, whichever occurred first (maximum up to 11.1 months) Time from date of randomization to the date of first confirmed PSA progression as per Prostate Cancer Clinical Trials Working Group 2 (PCWG2). For participant's whose PSA decreased at Week 13 after randomization, progression was defined as 25 percent (%) PSA increase relative to nadir or absolute increase of \>=2 nanogram/milliliter (ng/mL) above nadir. Progression was confirmed if another assessment measured at least 3 weeks later met the criterion as well. For participant's whose PSA did not decrease at Week 13 after randomization, progression was defined as 25% PSA increase relative to baseline assessed 12 weeks after baseline. Participants who were not known to have had a PFS event at the analysis date were censored at last PSA assessment date prior to data cutoff date.
Time to First Use of New Antineoplastic Therapy for Prostate Cancer From randomization until date of first use of any antineoplastic therapy (after last dose date of Period 2, maximum up to 22.3 months It was defined as time from randomization to the date of first use of subsequent antineoplastic therapy for prostate cancer. For participants who had not started subsequent antineoplastic therapy as of data analysis cutoff date, the time to first use of subsequent antineoplastic therapy was censored at the date of last assessment.
Change From Baseline in Quality of Life as Assessed by Functional Assessment of Cancer Therapy-Prostate (FACT-P) Prostate Cancer Domain Scores Baseline, Week 9, 13, 17, 21, 25, 29, 33, 37, 41, 45, 49, 53, 57, 61, 65, 69, 73, 77, 81, 85, 89 The FACT-P is a multidimensional, self-reported quality of life instrument consisting of 27 core items that assess participant function in 4 domains: physical, social/family, emotional, functional well-being, and supplemented by 12 site-specific items to assess for prostate-related symptoms. Each item is rated on a 0 to 4 Likert-type scale, and then combined to produce subscale scores for each domain. Total subscale score range for prostate cancer domain is from 0 (worst response) to 48 (best response), where higher score indicated better quality of life with fewer symptoms.
Change From Baseline in Quality of Life as Assessed by Functional Assessment of Cancer Therapy-Prostate (FACT-P) Functional Well-Being Domain Scores Baseline, Week 9, 13, 17, 21, 25, 29, 33, 37, 41, 45, 49, 53, 57, 61, 65, 69, 73, 77, 81, 85, 89 The FACT-P is a multidimensional, self-reported quality of life instrument consisting of 27 core items that assess participant function in 4 domains: physical, social/family, emotional, functional well-being, and supplemented by 12 site-specific items to assess for prostate-related symptoms. Each item is rated on a 0 to 4 Likert-type scale, and then combined to produce subscale scores for each domain. Total subscale score range for functional well-being domain is from 0 (worst response) to 28 (best response), where higher score indicate better quality of life.
Time to Degradation of the Functional Assessment of Cancer Therapy-Prostate (FACT-P) Global Score From randomization up to maximum of 18.4 months Time to degradation of FACT-P was defined as the time from randomization to first assessment with at least a 10-point decrease from baseline in the global FACT-P score for each participant. The FACT-P is a multidimensional, self-reported quality of life instrument consisting of 27 core items that assess participant function in 4 domains: physical, social/family, emotional, and functional well-being, and supplemented by 12 site-specific items to assess for prostate-related symptoms. Each item is rated on a 0 to 4 Likert-type scale, and then combined to produce subscale scores for each domain, as well as a global quality of life score which is the sum of all 5 domain scores and ranges from 0 to 156 with higher scores representing better quality of life. Participants with no score degradation at the time of analysis data cutoff were censored at the date of last assessment showing no degradation.
Trial Locations
- Locations (89)
Dana Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
Box Hill Hospital
🇦🇺Box Hill, Victoria, Australia
Universitaire Ziekenhuizen Leuven
🇧🇪Leuven, Belgium
Icon Cancer Care
🇦🇺South Brisbane, Queensland, Australia
Monash Medical Centre
🇦🇺Clayton, Victoria, Australia
SCDU Oncologia Medica II Pad, A.O.U. San Luigi Gonzaga
🇮🇹Orbassano TO, Italy
Bratislavske radiodiagnosticke centrum,a.s.
🇸🇰Bratislava, Slovakia
CUIMED, s.r.o., urologicka ambulancia
🇸🇰Bratislava, Slovakia
Frederiksberg Hospital
🇩🇰Frederiksberg, Denmark
Brigham & Women's Hospital
🇺🇸Boston, Massachusetts, United States
Urology of Virginia, PLLC
🇺🇸Virginia Beach, Virginia, United States
Border Medical Oncology Research Unit
🇦🇺Albury, New South Wales, Australia
Ramsay Health Care Australia Pty Ltd
🇦🇺Albury, New South Wales, Australia
Terry White Chemist
🇦🇺Albury, New South Wales, Australia
Beth Israel Deaconess Medical Center
🇺🇸Boston, Massachusetts, United States
eResearch Technology
🇺🇸Philadelphia, Pennsylvania, United States
Regional Imaging Border
🇦🇺Albury, New South Wales, Australia
Concord Cancer Centre, Medical Oncology Department
🇦🇺Concord, New South Wales, Australia
Concord Hospital Clinical Trials Pharmacy
🇦🇺Concord, New South Wales, Australia
Epic Pharmacy Lismore
🇦🇺Lismore, New South Wales, Australia
Macquarie University Hospital Pharmacy
🇦🇺North Ryde, New South Wales, Australia
Macquarie University
🇦🇺North Ryde, New South Wales, Australia
Port Macquarie Base Hospital,North Coast Cancer Institute
🇦🇺Port Macquarie, New South Wales, Australia
Epic Pharmacy Port Macquarie base hospital
🇦🇺Port Macquarie, New South Wales, Australia
North Shore Radiology and Nuclear Medicine
🇦🇺St Leonards, New South Wales, Australia
Sydney Adventist Hospital
🇦🇺Wahroonga, New South Wales, Australia
Regional Imaging
🇦🇺West Albury, New South Wales, Australia
Northern NSW Local Health District
🇦🇺Tweed Heads, New South Wales, Australia
Queensland Diagnostic Imaging
🇦🇺Tweed Heads, New South Wales, Australia
Westmead Hospital
🇦🇺Westmead, New South Wales, Australia
River City Pharmacy - APHS
🇦🇺Auchenflower, Queensland, Australia
Icon Cancer Care Wesley
🇦🇺Auchenflower, Queensland, Australia
Icon Cancer Care Chermside
🇦🇺Chermside, Queensland, Australia
Gold Coast Radiology PTY LTD
🇦🇺Hope Island, Queensland, Australia
Icon Cancer Care South Brisbane
🇦🇺South Brisbane, Queensland, Australia
Adelaide Cancer Centre
🇦🇺Kurralta Park, South Australia, Australia
South Coast Radiology
🇦🇺Tugun, Queensland, Australia
Ashford Cancer Centre Research
🇦🇺Kurralta Park, South Australia, Australia
Cancer Care SA Pty Ltd
🇦🇺Kurralta Park, South Australia, Australia
Moorabbin Radiology
🇦🇺Bentleigh East, Victoria, Australia
Tenpharm Pty Ltd trading as EPIC Pharmacy Tennyson
🇦🇺Kurralta Park, South Australia, Australia
Cabrini Health - Cabrini Hospital
🇦🇺Malvern, Victoria, Australia
Algemeen Ziekenhuis Groeninge
🇧🇪Kortrijk, West-vlaanderen, Belgium
Cliniques universitaires saint-Luc
🇧🇪Bruxelles, Belgium
Border Medical Oncology
🇦🇺Wodonga, Victoria, Australia
Arhus Universitetshospital
🇩🇰Arhus N, Denmark
Rigshospitalet CPC 7521
🇩🇰Copenhagen, Norrebro, Denmark
Rigshospitalet
🇩🇰Copenhagen, Denmark
Helsingin yliopistollinen keskussairaala, Meilahden sairaala
🇫🇮Helsinki, Finland
Oulun yliopistollinen sairaala
🇫🇮Oulu, Finland
Tampereen yliopistollinen Sairaala
🇫🇮Tampere, Finland
U.O. Oncologia Medica, IRCCS Istituto Scientifico Romagnolo per lo Studio e la Cura
🇮🇹Meldola, FC, Italy
Medicina Nucleare, Azienda Ospedaliera "Istituti Ospitalieri" di Cremona
🇮🇹Cremona, Italy
Servizio di Radiologia, Azienda Ospedaliera "Istituti Ospitalieri" di Cremona
🇮🇹Cremona, Italy
Institut Gustave Roussy - Service d'Urologie
🇫🇷Villejuif Cedex, France
Struttura Complessa di Oncologia, Azienda Socio Sanitaria Territoriale di Cremona
🇮🇹Cremona, Italy
Laboratorio Farmaci Antiblastici
🇮🇹Meldola (FC), Italy
UO Radiologia
🇮🇹Meldola (FC), Italy
SS Medicina Nucleare, A.O.U. San Luigi Gonzaga
🇮🇹Orbassano TO, Italy
SCDU Radiodiagnostica, A.O.U. San Luigi Gonzaga
🇮🇹Orbassano TO, Italy
Azienda Ospedaliera S. Camillo Forlanini, UOC per il governo clinico in Oncologia Medica
🇮🇹Roma, Italy
UOC Radiologia Piasta, Azienda Ospedaliera S. Camillo Forlanini
🇮🇹Roma, Italy
Fakultna nemocnica s poliklinikou F.D. Roosevelta
🇸🇰Banska Bystrica, Slovakia
Institut nuklearnej a molekularnej mediciny
🇸🇰Banska Bystrica, Slovakia
Jessenius-diagnosticke centrum, a.s.
🇸🇰Nitra, Slovakia
Uroexam, spol. s r.o., Urologicka ambulancia
🇸🇰Nitra, Slovakia
Univerzitna nemocnica martin
🇸🇰Martin, Slovakia
IZOTOPCENTRUM, s.r.o.
🇸🇰Nitra, Slovakia
CO Badalona-Instituto Germans Trias i Pujol
🇪🇸Badalona, Barcelona, Spain
GAMMALAB, spol.s r.o., Oddelenie nuklearnej mediciny
🇸🇰Trnava, Slovakia
ICO Badalona-Instituto Germans Trias i Pujol
🇪🇸Badalona,, Barcelon, Spain
Hospital Universitari Parc Tauli
🇪🇸Sabadell, Barcelona, Spain
Urologmottagningen
🇸🇪Orebro, Sweden
Hospital Universitario Son Espases
🇪🇸Palma, Islas Baleares, Spain
Hospital Clinic de Barcelona
🇪🇸Barcelona, Spain
ALTAHIA, Xarxa Assistencial Universitaria de Manresa
🇪🇸Manresa, Barcelona, Spain
Hospital del Mar
🇪🇸Barcelona, Spain
Oriola
🇸🇪Molnlycke, Sweden
Urologiska kliniken
🇸🇪Malmo, Sweden
Apoteket AB Kliniska Provningar Molnlycke
🇸🇪Molnlycke, Sweden
Rontgenkliniken
🇸🇪Orebro, Sweden
The Royal Marsden NHS Foundation Trust
🇬🇧London, United Kingdom
East and North Hertfordshire NHS Trust
🇬🇧Northwood, Middlesex, United Kingdom
Velindre NHS Trust
🇬🇧Cardiff, United Kingdom
University College London Hospitals NHS Foundation Trust
🇬🇧London, United Kingdom
University College Hospitals NHS Trust
🇬🇧London, United Kingdom
Oxford University Hospitals NHS Trust
🇬🇧Oxford, United Kingdom
Hospital Universitario Madrid Sanchinarro
🇪🇸Madrid, Spain
Royal North Shore Hospital
🇦🇺St Leonards, New South Wales, Australia