A Study to Determine Enzalutamide Long-term Safety and Efficacy After Anti-androgen Therapy for CRPC

Study Overview
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Brief Summary
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This is a prospective observational study to evaluate effectiveness and safety of Enzalutamide for Castration Resistant Prostate Cancer (CRPC) patients who decided to administer Enzalutamide after anti-androgen therapy. CRPC Patients who are observed PSA or disease progression after anti-androgen therapy and decided to administrate Enzalutamide will dose the Enzalutamide 160 mg orally once daily and observed the practical treatment. Total research term is for 4 years, consists of 2-year case registration terms and 2-year observational terms.

Official Title
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A Study to Determine Enzalutamide Long-term Safety and Efficacy After Anti-androgen Therapy for CRPC

Conditions
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Castration Resistant Prostate Cancer (CRPC)

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with histologically or cytologically confirmed prostate cancer. Patients who are receiving or received continuous androgen deprivation therapy using both gonadotropin-releasing hormone (GnRH) agonist and antagonist (medical castration), or both testicles removal by surgery (surgical castration). Castration resistant prostate cancer (CRPC) patients who are observed disease progression after castration treatment and implied the treatment resistant. CRPC patients who conducted anti-androgen alternating therapy as shown below 1) and are observed one or more of disease progression shown as below 2) during or after the therapy and decided to administer enzalutamide. Note 1) anti-androgen alternating therapy is defined as the therapy of flutamide administration after bicalutamide. Note 2) Disease progression criteria during or after anti-androgen alternating therapy ① PSA progression during or after anti-androgen alternating therapy: PSA increased more than 25% compare to the lowest test results after initial dose of anti-androgen alternating therapy (flutamide) and the increasing is more than 2ng/ml. ②Confirmed disease progression of soft tissue lesion defined as RECIST v1.1. ③Confirmed disease progression of bone lesion defined as 2 or more of new appearance of bone lesion on bone scintigraphy. Patients with the Eastern Cooperative Oncology Group (ECOG) performance status 0-2 Patients who have signed written informed consent to participate in this study Exclusion Criteria: Patients who is administering or have administration history of enzalutamide, abiraterone, docetaxel or cabazitaxel Patients with history of seizure or predisposing disease of seizure Patients with severe liver dysfunction Patients with a previous history of hypersensitivity to any component of drugs which will be administered in this study Patients who considered to be inappropriate for the study participation by the investigator

Ages Eligible for Study
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Minimum Age: 20 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival (OS) | OS is defined as time from date of initial dose until date of death from any cause. In the case of any new chemotherapy added or changed to another treatment to prostate cancer, the conducted date will be applied. When patient is no longer traceable, the final confirmed date as alive will be applied to OS. | 50 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Prostate Specific Antigen-progression-free survival (PSA-PFS) | Prostate specific antigen (PSA) progression-free survival is defined as time from date of initial dose until the date of first confirmed PSA progression (an increase in PSA of >= 25% and >= 2 ng/ml above the nadir after initial dose) or date of death from any cause, whichever comes first. In the case of any new chemotherapy added or changed to another treatment to prostate cancer, the conducted date will be applied. | 50 months | 
| Progression-free survival (PFS) | PFS is defined as time from date of initial dose until the date of first confirmed progression or date of death from any cause, whichever comes first. Progression is defined as followed:① A growth of primary lesion or appearance of neopathy by image diagnosis, aggravation of general condition・PS decrease or noticable weight loss which investigator assess as progression. ②Unmeasurable or difficult to measure lesion which newly appeared or investigator assess as obvious aggravation. ③ In the case of any new chemotherapy added or changed to another treatment to prostate cancer | 50 months | 
| Time to Treatment Failure (TTTF) | TTTF is defined as time from date of initial dose until the date of any new chemotherapy added or changed to another treatment to prostate cancer. | 50 months | 
| Time-to-PSA-progression (TTPP) | TTPP is defined as time from date of initial dose until the date of first confirmed PSA progression (an increase in PSA of >= 25% and >= 2 ng/ml above the nadir after initial dose). In the case of any new chemotherapy added or changed to another treatment to prostate cancer, the conducted date will be applied. | 50 months | 
| PSA response rate | PSA response rate is defined as ratio of patients who have an decrease in PSA of >= 50% above baseline since initial dose. | 50 months | 
| Time to First Symptomatic Skeletal Events (TTFS) | TTFS is defined as time from date of initial dose until the date of first confirmed skeletal-related event. In the case of any new chemotherapy added or changed to another treatment to prostate cancer, the conducted date will be applied. Symptomatic Skeletal Events (SSE) defined as followed: ・Operation of EBRT External Beam Radiation Therapy (EBRT) to mitigate skeletal events ・New appearance of symptomatic pathological fracture ・Appearance of spinal cord compression ・Orthopedic intervention related to tumor | 50 months | 
| The state of administration | The state of administration is assessed by Relative Dose Intensity (RDI). RDI is calculated by dosage and dosing period. RDI calculation formula =∑ (daily dosage ×dosing days) / (160mg ×total dosing number of days). ∑ means all total dose which adds up in different dosage. Total number of days mean treatment term of this trial. | 2 years | 
| Safety assessment | Safety assessment by the incidence and severity of adverse events as assessed by Japanese version of the Common Terminology Criteria for Adverse Events (CTCAE) version 4.00 | 50 months |