A Study to Assess the Benefit of Treatment Beyond Progression With Enzalutamide in Men Who Are Starting Treatment With Docetaxel After Worsening of Their Prostate Cancer When Taking Enzalutamide Alone

Astellas Pharma Europe Ltd.688 enrolled

Overview

The purpose of the study was to understand if there was benefit in continued treatment with a medicine called enzalutamide, when starting treatment with docetaxel and prednisolone (a standard chemotherapy for prostate cancer), after the prostate cancer had gotten worse when treated with enzalutamide alone.

The study was conducted in consecutive periods of open label treatment with enzalutamide followed by randomized double-blind treatment with continued enzalutamide or placebo, in combination with docetaxel and prednisolone. Open Label (Period 1) Participants received open label treatment (OL) with enzalutamide. At week 13, all participants were assessed by prostate-specific antigen (PSA) and imaging. Participants with no confirmed PSA response or evidence of radiographic progression were ineligible for participation in Period 2 and typically had safety follow up; however, Period 1 treatment continued for some participants as long as the investigator considered it to be of clinical benefit (stopping on initiation of any new antineoplastic therapy). Participants with confirmed PSA response continued Period 1 until disease progression. Enrollment to Period 2 ceased after approximately 274 participants had been enrolled or 182 primary endpoint events had been reached, whichever occurred first. Participants who were not randomized into period 2 at this time continued to receive open label treatment in an extension period. Randomization (Double Blind \[DB\]) (Period 2) Participants with confirmed disease progression on enzalutamide alone who continued to meet all eligibility criteria proceeded to randomization. Treatment allocation was in a 1:1 ratio, stratified by disease progression in Period 1 to the following treatments: * Enzalutamide with docetaxel and prednisolone * Placebo with docetaxel and prednisolone Any ongoing participants in Period 2 at the point of unblinding in the enzalutamide+docetaxel arm that were still receiving and benefitting from enzalutamide treatment, had the option to continue treatment via an extension period.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

Conditions

Metastatic Castration Resistant Prostate Cancer

Interventions

EnzalutamideDRUG

Oral

DocetaxelDRUG

intravenous infusion

PrednisoloneDRUG

Oral

PlaceboDRUG

Eligibility

Sex: MALEMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Histologically confirmed adenocarcinoma of the prostate without neuroendocrine differentiation or small cell features; * Ongoing androgen deprivation therapy (ADT) with a luteinizing hormone-releasing hormone (LHRH) agonist or antagonist at a stable dose and schedule within 4 weeks of initiation of investigational medicinal product (IMP), or bilateral orchiectomy (i.e., surgical or medical castration); * Metastatic disease documented by at least 2 bone lesions on bone scan, or soft tissue disease documented by computed tomography (CT)/magnetic resonance imaging (MRI); * Progressive disease at study entry defined as the following occurring in the setting of castrate levels of testosterone: Prostate specific antigen (PSA) progression defined by a minimum of three rising PSA levels with an interval of ≥ 1 week between each determination. * Asymptomatic or minimally symptomatic prostate cancer (Brief Pain Inventory - Short Form (BPI-SF) question 3 score of \< 4); * Eastern Cooperative Oncology Group (ECOG) performance score of 0-1; * Estimated life expectancy of ≥ 12 months; * Be suitable and willing to receive chemotherapy as part of the trial; * Able to swallow the IMP and comply with study requirements; * Subject agreed not to participate in another interventional study while on treatment. Exclusion Criteria: * Prior treatment with the following agents for the treatment of prostate cancer: Aminoglutethimide; Ketoconazole; Abiraterone; Enzalutamide or participation in a clinical trial of enzalutamide; 223Ra, 89Sr, 153Sm, 186Re/188Re; Immunomodulatory therapies; Cytotoxic chemotherapy; Participation in a clinical trial of an investigational agent that inhibits the AR or androgen synthesis unless the treatment was placebo; * Current or prior treatment within 4 weeks prior to initiation of investigational medicinal product (IMP) with the following agents for the treatment of prostate cancer: Antiandrogens; 5-α reductase inhibitors; Estrogens; Anabolic steroids; Drugs with antiandrogenic properties; Progestational agents; * Subject had received investigational therapy within 28 days or 5 half-lives whichever was longer, prior to initiation of IMP; * Use of opiate analgesia for pain from prostate cancer within 4 weeks prior to initiation of IMP; * Radiation therapy to bone lesions or prostatic bed within 4 weeks prior to initiation of IMP; * Major surgery within 4 weeks prior to initiation of IMP; * History of seizure or any condition that may predispose to seizures at any time in the past. History of loss of consciousness or transient ischemic attack within 12 months prior to Screening; * Known or suspected brain metastasis or active leptomeningeal disease; * History of another malignancy within the previous 5 years other than non-melanoma skin cancer; * Clinically significant cardiovascular disease; * Gastrointestinal disorders affecting absorption; * Medical contraindications to the use of prednisolone or docetaxel; * Allergies to any of the active ingredients or excipients in the study drugs

Locations (89)

Outcomes

Primary Outcomes

Progression Free Survival (PFS)

PFS: time from randomization (Period 2 Week 1) to earliest progression event. Progression is defined as radiographic progression, unequivocal clinical progression, or death on study. Radiographic progression is defined for bone disease by appearance of ≥ 2 new lesions on whole-body radionuclide bone scan per Prostate Cancer Clinical Trials Working Group 2 (PCWG2) criteria (i.e., unconfirmed progressive disease) that needs to be confirmed in the next assessment (i.e., progressive disease in the next assessment) or for soft tissue disease by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. Unequivocal clinical progression is defined as new onset cancer pain requiring chronic administration of opiate analgesia or deterioration from prostate cancer of Eastern Cooperative Oncology Group (ECOG) performance status score to ≥ 3, or initiation of subsequent lines of cytotoxic chemotherapy or radiation therapy or surgical intervention due to complications of tumor progression.

Time frame: From date of randomization to the earliest of either documented disease progression (median duration: 35 weeks)

Secondary Outcomes

Time to Prostate-specific Antigen (PSA) Progression

Time to PSA progression, defined as the time from randomization (Period 2 Week 1) to the date of the first PSA value in Period 2 demonstrating progression (Period 2). The PSA progression date is defined as the date that a ≥ 25% increase and an absolute increase of ≥ 2 ng/mL above the nadir recorded in Period 2 is documented, which must be confirmed by a second consecutive value obtained at least 3 weeks later.

Time frame: From date of randomization to the first PSA value (median duration: 35 weeks)

Prostate-specific Antigen (PSA) Response

PSA response, defined as a decrease in percentage change from randomization (Period 2 Week 1) of 50% or more. PSA response was derived at Week 13 and at any time after randomization in Period 2. PSA response at any time is defined as a decrease in percentage change from randomization (Period 2 Week 1) at any time after randomization of 50% or more. Percentage of participants with PSA response was reported.

Data from ClinicalTrials.gov

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