Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

All Conditions

Symptoms and General Pathology

Prostatic Neoplasms

Disease Progression

Genital Neoplasms, Male

Urogenital Neoplasms

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Prostatic Diseases

Male Urogenital Diseases

Antineoplastic Agents

All Drugs and Chemicals

Anti-Inflammatory Agents

Antiemetics

Neuroprotective Agents

Gastrointestinal Agents

Abiraterone Acetate

Prednisone

Prednisolone

Methylprednisolone

Methylprednisolone Acetate

Methylprednisolone Hemisuccinate

Prednisolone acetate

Prednisolone hemisuccinate

Prednisolone phosphate

Glucocorticoids

Hormones

Hormone Antagonists

Antineoplastic Agents, Hormonal

Enzyme Inhibitors

Cytochrome P-450 Enzyme Inhibitors

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 (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

Sugar pill manufactured to mimic Enzalutamide 40 mg capsule

Placebo for Enzalutamide

Pfizer CT.gov Call Center

Medical Director

The purpose of this study is to determine if continued treatment with Enzalutamide is effective in patients with metastatic prostate cancer.

Safety Study of Continued Enzalutamide Treatment In Prostate Cancer Patients

A PHASE 4, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED STUDY OF CONTINUED ENZALUTAMIDE TREATMENT BEYOND PROGRESSION IN PATIENTS WITH CHEMOTHERAPY-NAÏVE METASTATIC CASTRATION-RESISTANT PROSTATE CANCER

Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.

An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment emergent are events between first dose of study drug and up to 30 days after last dose of study drug that were absent before treatment, or worsened during the treatment period relative to the pretreatment state. AEs included both serious and non-serious.

An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Outcome of an AE was response to a question answered by the investigator: 'Is the AE leading to study discontinuation or death?' as 'yes'.

Treatment-related AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent were events between first dose of study drug and up to 30 days after last dose of study drug that were absent before treatment or that worsened relative to pre-treatment state. Relatedness to study drug was assessed by the investigator.

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.

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.

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 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 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.

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.

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.

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.

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.

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.

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.

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.

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.

Astellas Pharma Inc

Medivation LLC, a wholly owned subsidiary of Pfizer Inc.

Pfizer

Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. The all-cause mortality data was evaluated on all enrolled participants while the data for SAEs and other AEs were evaluated for safety population.

Participants who only received enzalutamide 160 mg as four 40 mg capsules, orally once daily in the study.

Enzalutamide 160 mg

Participants who received (after switching from enzalutamide) abiraterone 1000 mg as four 250 mg tablets, orally once daily and prednisone 10 mg administered as two 5 mg tablets, orally twice daily in the study.

Enzalutamide Crossing Over to Abiraterone + Prednisone

Participants who received enzalutamide 160 mg as four 40 mg capsules, orally once daily along with abiraterone 1000 mg as four 250-mg tablets, orally once daily and prednisone 5 mg tablet, orally twice daily in the study.

Enzalutamide 160mg+Abiraterone 1000mg+ Prednisone 10mg

Participants who received placebo matched to enzalutamide as four 40 mg capsules, orally once daily along with abiraterone 1000 mg as four 250-mg tablets, orally once daily and prednisone 5 mg tablet, orally twice daily in the study.

Placebo + Abiraterone 1000 mg + Prednisone 10mg

Participants received enzalutamide 160 mg as four 40 mg capsules, orally once daily until disease progression (as defined by radiographic imaging or unequivocal clinical progression or death on study), intolerable toxicity, or participant withdrawal, whichever occurred first. Participants were followed-up until 30 days after last dose of study drug or before initiation of a new antitumor treatment, whichever occurred first.

Age, Continuous

Sex: Female, Male

ITT (Intent to treat) population included all participants randomly assigned to study treatment.

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Participants with confirmed PSA progression at Week 21 in open label period, received enzalutamide 160 mg as four 40 mg capsules, orally once daily along with abiraterone 1000 mg as four 250-mg tablets, orally once daily and prednisone 5 mg tablet, orally twice daily in double blind treatment period, up to disease progression (as defined by radiographic imaging or unequivocal clinical progression or death on study), intolerable toxicity, or participant withdrawal, whichever occurred first. Participants were followed up for 16 weeks at 4-week interval after discontinuation of study drug for survival and subsequent antineoplastic therapy for prostate cancer.

Participants with confirmed PSA progression at Week 21 in open label period, received placebo matched to enzalutamide as four 40 mg capsules, orally once daily along with abiraterone 1000 mg as four 250-mg tablets, orally once daily and prednisone 5 mg tablet, orally twice daily in double blind treatment period, up to disease progression (as defined by radiographic imaging or unequivocal clinical progression or death on study), intolerable toxicity, or participant withdrawal, whichever occurred first. Participants were followed up for 16 weeks at 4-week interval after discontinuation of study drug for survival and subsequent antineoplastic therapy for prostate cancer.

Placebo+Abiraterone 1000mg+ Prednisone 10mg

ITT population included all participants randomly assigned to study treatment.

Progression Free Survival (PFS)

Time to Prostate Specific Antigen (PSA) Progression

This analysis is reported for participants with \>=50% decrease from baseline in PSA response.

This analysis is reported for participants with \>=30% decrease from baseline in PSA response.

>= 50%

>= 30%

Evaluable ITT population included all participants with a PSA value at baseline of Period 2 and at least 1 post baseline assessment. Here, N signifies those participants who were evaluable for this outcome measure.

Prostate Specific Antigen (PSA) Response Rate

This analysis is reported for participants with CR+PR.

This analysis is reported for participants with CR+PR+SD.

CR + PR

CR + PR + SD

ITT population (with measurable disease at screening) included all participants randomly assigned to study treatment. Here, N signifies those participants who were evaluable for this outcome measure.

Objective Response Rate (ORR)

ITT population included all participants randomly assigned to study treatment. Here, N signifies those participants who were evaluable for this outcome measure.

Rate of Pain Progression

Time to First Use of New Antineoplastic Therapy for Prostate Cancer

Baseline

Change at Week 9

Change at Week 13

Change at Week 17

Change at Week 21

Change at Week 25

Change at Week 29

Change at Week 33

Change at Week 37

Change at Week 41

Change at Week 45

Change at Week 49

Change at Week 53

Change at Week 57 (n =17, 13)

Change at Week 61

Change at Week 65

Change at Week 69

Change at Week 73

Change at Week 77

Change at Week 81

Change at Week 85

Change at Week 89

Change From Baseline in Quality of Life as Assessed by Functional Assessment of Cancer Therapy-Prostate (FACT-P) Global Score

Change at Week 57

Change From Baseline in Quality of Life as Assessed by Functional Assessment of Cancer Therapy-Prostate (FACT-P) Social/Family Well-Being Domain Scores

Change From Baseline in Quality of Life as Assessed by Functional Assessment of Cancer Therapy-Prostate (FACT-P) Emotional Well-Being Domain Scores

Change From Baseline in Quality of Life as Assessed by Functional Assessment of Cancer Therapy-Prostate (FACT-P) Functional Well-Being Domain Scores

Change From Baseline in Quality of Life as Assessed by Functional Assessment of Cancer Therapy-Prostate (FACT-P) Prostate Cancer Domain Scores

Change From Baseline in Quality of Life as Assessed by Functional Assessment of Cancer Therapy-Prostate (FACT-P) Physical Well-Being Domain Scores

Evaluable ITT population included all participants with a PSA value at baseline of Period 2 and at least 1 post baseline assessment.

Time to Degradation of the Functional Assessment of Cancer Therapy-Prostate (FACT-P) Global Score

SAEs

Safety population included all participants who received any amount of study drug.

Percentage of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)

Drug Discontinuation with Enzalutamide or Placebo

Drug Discontinuation with Abiraterone

Drug Discontinuation with Prednisone

Participants who received (after switching from enzalutamide), abiraterone 1000 mg as four 250 mg tablets, orally once daily and prednisone 10 mg administered as two 5 mg tablets, orally twice daily in the study.

Percentage of Participants With Adverse Events (AEs) Leading to Study Drug Discontinuation

Participants who received enzalutamide (after switching from enzalutamide), abiraterone 1000 mg as four 250 mg tablets, orally once daily and prednisone 10 mg administered as two 5 mg tablets, orally twice daily in the study.

Percentage of Participants With Adverse Events (AEs) Leading to Death

TEAEs related to Enzalutamide or Placebo

TEAEs related to Abiraterone

TEAEs related to Prednisone

SAEs related to Enzalutamide or Placebo

SAEs related to Abiraterone

SAEs related to Prednisone

Safety population included all participants who received any amount of study drug. "Number Analyzed" signifies participants evaluable for the specified categories for respective arms.

Percentage of Participants With Treatment-Emergent Treatment-Related Adverse Events (AEs) and Serious Adverse Events (SAEs)

Participants who only received enzalutamide 160 mg as four 40 mg capsules, orally once daily until disease progression (as defined by radiographic imaging or unequivocal clinical progression or death on study), intolerable toxicity, or participant withdrawal, whichever occurred first. Participants were followed-up until 30 days after last dose of study drug or before initiation of a new antitumor treatment, whichever occurred first.

Participants who received (after switching from enzalutamide), in second open label period, abiraterone 1000 mg as four 250 mg tablets, orally once daily and prednisone 10 mg administered as two 5 mg tablets, orally twice daily until disease progression (as defined by radiographic imaging or unequivocal clinical progression or death on study), intolerable toxicity, or participant withdrawal, whichever occurred first. Participants were followed-up until 30 days after last dose of study drug or before initiation of a new antitumor treatment, whichever occurred first.

Enzalutamide 160 mg Crossing Over to Abiraterone 1000 mg+ Prednisone 10 mg

Participants with confirmed prostate-specific antigen (PSA) progression at Week 21 in open label period, received enzalutamide 160 mg as four 40 mg capsules, orally once daily along with abiraterone 1000 mg as four 250-mg tablets, orally once daily and prednisone 5 mg tablet, orally twice daily in double blind treatment period, up to disease progression (as defined by radiographic imaging or unequivocal clinical progression or death on study), intolerable toxicity, or participant withdrawal, whichever occurred first. Participants were followed up for 16 weeks at a 4-week interval after discontinuation of study drug for survival and subsequent antineoplastic therapy for prostate cancer.

Enzalutamide 160 mg+ Abiraterone 1000 mg+ Prednisone 10mg

Participants with confirmed PSA progression at Week 21 in open label period, received placebo matched to enzalutamide as four 40 mg capsules, orally once daily along with abiraterone 1000 mg as four 250-mg tablets, orally once daily and prednisone 5 mg tablet, orally twice daily in double blind treatment period, up to disease progression (as defined by radiographic imaging or unequivocal clinical progression or death on study), intolerable toxicity, or participant withdrawal, whichever occurred first. Participants were followed up for 16 weeks at a 4-week interval after discontinuation of study drug for survival and subsequent antineoplastic therapy for prostate cancer.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Safety Study of Continued Enzalutamide Treatment In Prostate Cancer Patients	NCT01995513	Prostate Cancer	Enzalutamide Abiraterone Placebo for Enz... Prednisone	18 Years -	Pfizer
Safety Study of Continued Enzalutamide Treatment In Prostate Cancer Patients	NCT01995513	Prostate Cancer	Enzalutamide Abiraterone Placebo for Enz... Prednisone	18 Years -	Pfizer

Spots Global Cancer Trial Database for placebo for enzalutamide