Enzalutamide Treatment of Metastatic Castration-Resistant Prostate Cancer Patients after Abiraterone Acetate

Phase 1

• Conditions: Metastatic progressive castration-resistant prostate cancer; MedDRA version: 16.1Level: PTClassification code 10062904Term: Hormone-refractory prostate cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2013-002271-17-ES
• Lead Sponsor: Astellas Pharma Europe B.V.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2014-04-02
• Last Update Posted: 23 October 2017

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Male
• Target Recruitment: 200

Inclusion Criteria

1. Subject has histologically confirmed adenocarcinoma of the prostate without neuro-endocrine differentiation or small cell features.
2. Subject has metastatic disease documented by bone scan or by soft tissue disease observed by CT/MRI.
3. Subject has a serum testosterone of ? 1.7 nmol/L (or ? 50 ng/dL) at screening.
4. In the setting of castrate levels of testosterone ?1.7 nmol/L (or ?50 ng/dL), subject has progressive disease at study entry defined as PSA rise determined by a minimum of 2 rising PSA levels with an interval of ? 1 week between each assessment. The PSA value at the screening visit should be ? 2 ng/mL WITH or WITHOUT:
?Soft tissue disease progression defined by Response Evaluation Criteria In Solid Tumors (RECIST 1.1) at screening. Measurable disease is not required for entry. Lymph nodes
? 2 cm are considered measurable disease (PCWG2).
?Bone disease progression defined by at least 2 new lesions on bone scan at screening.
5. Subject must have received a minimum of 6 months of treatment with abiraterone acetate and has discontinued use at least 4 weeks prior to start of study drug at Day 1.
6. If the subject has received previous treatment with chemotherapy for prostate cancer, this must be limited to no more than one prior line of docetaxel, and must have been used prior to abiraterone acetate therapy.
7. Subject receives and will continue to receive ongoing androgen deprivation with LHRH analogue therapy throughout the course of the study or has had a bilateral orchiectomy.
Subject is asymptomatic or mildly symptomatic from prostate cancer:
?The score on BPI-SF Question #3 must be < 4.
?No use of opiate analgesics for prostate cancer-related pain currently or anytime within 4 weeks prior to screening.
(Please refer to the protocol to see the full list of criteria)
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 75
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 125

Exclusion Criteria

1. Subject has prior use of ketoconazole for the treatment of prostate cancer.
2. Subject has prior use of cabazitaxel.
3. Subject has prior use of enzalutamide.
4. Subject has received ANY anti-neoplastic therapy (including antiandrogens and chemotherapy) following abiraterone acetate discontinuation and prior to start of study drug at Day 1.
5. Subject has a known or suspected hypersensitivity to enzalutamide, or any components of the formulation used.
6. Subject has known or suspected brain metastases or active leptomeningeal disease.
7. Subject has history of seizure or any condition that may predispose to seizure (e.g., prior stroke or significant brain trauma).
8. Subject has history of loss of consciousness or transient ischemic attack within 12 months of screening.
9. Subject has concurrent disease or any clinically significant abnormality following the investigator?s review of the physical examination, electrocardiogram (ECG) and safety laboratory tests at screening, which in the judgment of the investigator would interfere with the subject's participation in this study or evaluation of study results.
10. Subject has a history of another invasive cancer within 3 years prior to screening, with the exception of non-melanoma skin cancers that have a remote probability of recurrence in the opinion of the Investigator in consultation with the medical monitor.
(Please refer to the protocol to see the full list of criteria)

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: Evaluation of radiographic progression-free survival (rPFS);Secondary Objective: Evaluation of overall survival (OS)<br>Evaluation of prostate-specific antigen (PSA) response<br>Evaluation of time to PSA progression<br>Evaluation of the safety of enzalutamide;Primary end point(s): Radiographic progression-free survival (rPFS);Timepoint(s) of evaluation of this end point: Time from first dose to the first objective evidence of radiographic disease progression or death from any cause, whichever occurs first. For subjects who are alive and free of radiographic progression at the time of the analysis data cut-off point, rPFS time will be censored on the date of the last radiographic assessment showing no evidence of progression prior to the analysis data cut-off point.

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): Overall survival (OS)<br><br>PSA response defined as the proportion of subjects with at least 50% decrease from baseline in PSA<br><br>Time to PSA progression (TPP);Timepoint(s) of evaluation of this end point: OS: Time from first dose to death from any cause. For subjects who are alive at the time of the analysis data cut-off point, OS time will be censored on the last date the subject is known to be alive.<br><br>PSA response: Timepoint when lowest PSA value is observed post-baseline.<br><br>TPP: Timepoint when ? 25% increase and an absolute increase of ? 2 µg/L are observed.