Safety and Efficacy Study of Enzalutamide in Patients With Nonmetastatic Castration-Resistant Prostate Cancer

Phase 3CompletedNCT02003924

Pfizer1,401 enrolled

Overview

The purpose of this study is to assess the safety and efficacy of enzalutamide in patients with non metastatic prostate cancer.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

1,401

Conditions

Nonmetastatic Castration-Resistant Prostate Cancer Prostate Cancer Cancer of the Prostate

Interventions

EnzalutamideDRUG

160 mg by mouth once daily

PlaceboDRUG

Sugar pill to mimic enzalutamide

Eligibility

Sex: MALEMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Histologically or cytologically confirmed adenocarcinoma of the prostate without neuroendocrine differentiation, signet cell, or small cell features; * Ongoing androgen deprivation therapy with a gonadotropin-releasing hormone (GnRH) agonist/antagonist or prior bilateral orchiectomy (medical or surgical castration); * Testosterone ≤ 50 ng/dL (≤ 1.73 nmol/L) at screening; * Progressive disease on androgen deprivation therapy at enrollment; * PSA and the screening PSA assessed by the central laboratory (central PSA) should be ≥ 2 µg/L (2 ng/mL: * PSA doubling time ≤ 10 months; * No prior or present evidence of metastatic disease; * Asymptomatic prostate cancer; * Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1; * Estimated life expectancy ≥ 12 months. Exclusion Criteria: * Prior cytotoxic chemotherapy; * Use of hormonal therapy or biologic therapy for prostate cancer (other than approved bone targeting agents and GnRH agonist/antagonist therapy) or use of an investigational agent within 4 weeks of randomization; * Known or suspected brain metastasis or active leptomeningeal disease; * History of another invasive cancer within 3 years of randomization; * Absolute neutrophil count \< 1000/μL, platelet count \< 100,000/μL, or hemoglobin \< 10 g/dL (6.2 mmol/L) at screening; * Total bilirubin ≥ 1.5 times the upper limit of normal; * Creatinine \> 2 mg/dL (177 µmol/L) at screening; * Albumin \< 3.0 g/dL (30 g/L) at screening; * History of seizure or any condition that may predispose to seizure; * Clinically significant cardiovascular disease; * Gastrointestinal disorder affecting absorption; * Major surgery within 4 weeks of randomization; * Hypersensitivity reaction to the active pharmaceutical ingredient or any of the capsule components, including Labrasol, butylated hydroxyanisole, and butylated hydroxytoluene; * Any concurrent disease, infection, or comorbid condition that interferes with the ability of the patient to participate in the trial, which places the patient at undue risk, or complicates the interpretation of data, in the opinion of the investigator or medical monitor.

Locations (397)

Outcomes

Primary Outcomes

Metastasis Free Survival (MFS)

MFS:time from randomization to first date of radiographic progression (RP) (by Blinded independent central radiology review \[BICR\]) at any time or death within 112 days of treatment discontinuation without evidence of RP.RP for bone disease:appearance of 1 or more metastatic lesions on bone scan.RP for soft tissue disease:per Response Evaluation Criteria in Solid Tumors,\[RECIST 1.1\])-at least a 20 percent (%) increase in the sum of diameters of target lesions,taking as reference the smallest sum on study (includes the baseline sum if smallest on study).Participants who did not have MFS event at the time of analysis data cut-off (28 June 2017) were censored at date of last assessment showing no objective evidence of RP prior to skeletal-related event or two or more consecutive missed tumor assessments. Participants who were randomized but later confirmed to have metastatic disease before randomization were censored on date of randomization. Analysis was based on Kaplan-Meier estimates.

Time frame: From randomization until radiographic progression at any time, or death within 112 days of treatment discontinuation, whichever occurred first (until the data cut-off date of 28 June 2017, maximum duration of treatment: 42.8 months)

Secondary Outcomes

Time to Prostate-Specific Antigen (PSA) Progression

Time to PSA progression was defined as the time from randomization to the date of first PSA value demonstrating progression, which was subsequently confirmed. For participants with PSA decline at Week 17, PSA progression was defined according to Prostate Cancer Working Group 2 (PCWG2) guidelines as the date that a 25% or greater increase and an absolute increase of 2 nanograms per milliliter (ng/mL) above the nadir (or baseline for participants with no PSA decline by Week 17) was documented, which was confirmed by a second consecutive value obtained at least 3 weeks or later. Participants without confirmed PSA progression at the time of analysis were right censored at the date of last PSA assessment before the analysis data cut-off date for the purposes of analysis. Analysis was based on Kaplan-Meier estimates.

Time frame: From randomization until first PSA progression (until the data cut-off date of 28 June 2017, maximum duration of treatment: 42.8 months)

Data from ClinicalTrials.gov

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Urological Associates of Southern Arizona, PC

Tucson, Arizona, United States

Ronald Reagan UCLA Medical Center

Los Angeles, California, United States

UCLA Clark Urology Center

Los Angeles, California, United States

University of California, Irvine Medical Center

Orange, California, United States

Urology Associates of San Luis Obispo, a Medical Group, Inc

San Luis Obispo, California, United States

Urology Associates, P.C.

Englewood, Colorado, United States

c/o Lynn Buchwalder

New Haven, Connecticut, United States

C/O Thomas Ferencz, RPh, BCOP, Smilow Cancer Hospital at Yale-New Haven

New Haven, Connecticut, United States

Smilow Cancer Center at Yale New Haven-Hospital

New Haven, Connecticut, United States

Yale New Haven Hospital

New Haven, Connecticut, United States

...and 387 more locations

Time to First Use of New Antineoplastic Therapy

Time to first use of new antineoplastic therapy was defined as the time from randomization to first use of new antineoplastic for prostate cancer. Participants not starting treatment with a new antineoplastic therapy at the time of analysis were right censored at the date of last assessment before the analysis data cutoff date for the purposes of analysis. Analysis was based on Kaplan-Meier estimates.

Time frame: From randomization until first use of new antineoplastic therapy(until the data cut-off date of 28 June 2017, maximum duration of treatment: 42.8 months)

Overall Survival

Overall survival (OS) was defined as the time (in months) from randomization to death from any cause. For participants who were alive at the time of the analysis data cutoff, OS time was censored at the last date the participant was known to be alive or analysis data cutoff date, whichever was earlier. Participants with no post baseline survival information were censored on the date of randomization. Analysis was based on Kaplan-Meier estimates.

Time frame: From randomization until death (up to a maximum of 68.8 months)

Time to Pain Progression

Pain was assessed using the score from the Brief Pain Inventory-Short Form (BPI-SF) question 3: "Please rate your pain by marking the box beside the number that best describes your pain at its worst in the last 24 hours." Time to this event was defined as the time from randomization to onset of pain progression, where pain progression was defined as a 2-point or more increase from baseline in the question 3 score. Participants without observed pain progression at the time of analysis were right censored at the date of last pain assessment for the purposes of analysis. Analysis was based on Kaplan-Meier estimates.

Time frame: From randomization until onset of pain progression (until the data cut-off date of 28 June 2017, maximum duration of treatment: 42.8 months)

Time to First Use of Cytotoxic Chemotherapy

Time to first use of cytotoxic chemotherapy was defined as the time from randomization to the first use of cytotoxic chemotherapy for prostate cancer. Participants not starting treatment with a cytotoxic chemotherapy for prostate cancer at the time of analysis were right censored at the date of last assessment before the analysis data cutoff date for the purposes of analysis. Analysis was based on Kaplan-Meier estimates.

Time frame: From randomization up to the first use of cytotoxic chemotherapy (until the data cut-off date of 28 June 2017, maximum duration of treatment: 42.8 months)

Chemotherapy-Free Disease Specific Survival

Chemotherapy-free disease-specific survival was defined as the time from randomization to first use of cytotoxic chemotherapy for prostate cancer or death due to prostate cancer as assessed by the investigator. Participants not starting treatment with a cytotoxic chemotherapy or not known to have died due to prostate cancer at the time of analysis were right censored at the date of last assessment before the analysis data cutoff date for the purposes of analysis. Analysis was based on Kaplan-Meier estimates.

Time frame: From randomization up to first use of cytotoxic chemotherapy for prostate cancer or death due to prostate cancer (until the data cut-off date of 28 June 2017, maximum duration of treatment: 42.8 months)

Chemotherapy-Free Survival

Chemotherapy-free survival was defined as the time from randomization to first use of cytotoxic chemotherapy for prostate cancer or death due to any cause. Participants not starting treatment with a cytotoxic chemotherapy or not known to have died at the time of analysis were censored at the date of last assessment before the analysis data cutoff date for the purposes of analysis. Analysis was based on Kaplan-Meier estimates.

Time frame: From randomization up to first use of cytotoxic chemotherapy for prostate cancer or death due to any cause (until the data cut-off date of 28 June 2017, maximum duration of treatment: 42.8 months)

Percentage of Participants With Prostate Specific Antigen (PSA) Response

PSA response was calculated at each visit as a decline from baseline in PSA (ng/mL) to the maximal PSA response with thresholds at 50% and 90%. Additionally, PSA response was assessed as a decline to undetectable levels, where undetectable level was defined as below the limit of quantification of the centrally assessed PSA results (the lower limit of quantification was 0.02 ng/mL). PSA response was confirmed by a second consecutive value at least 3 weeks later.

Time frame: From randomization until first PSA progression (until the data cut-off date of 28 June 2017, maximum duration of treatment: 42.8 months)

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

The FACT-P questionnaire 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 prostate-related symptoms. Each item was 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 ranged from 0 to 156 where higher scores represented better quality of life.