Japanese Research for Patients With Non-metastatic Castration Resistant Prostate Cancer - Enzalutamide

Study Overview
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Brief Summary
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The purpose of this study is to investigate the efficacy and safety of enzalutamide in patients with non-metastatic castration resistant prostate cancer. The total duration of the study will be 5 years. All patients will receive enzalutamide 160 mg (four 40 mg capsules) orally once daily. The treatment will be started at Visit 0 within one week after enrollment. Visit 1 is at 2 weeks after the treatment started; clinical assessments are conducted on adverse events and the Japanese version of the Functional Assessment of Cancer Therapy-Prostate (FACT-P) scales. Patients who are considered to be adequate by the investigator can continue the treatment with 12-week cycle visit (counted from initial dose) until patients meet withdrawal criteria. Patients will be followed up at 2 and 3 years after enrollment and at 3 years after the last participant enrollment. The end of the study is defined as follow-up assessment date at 3 years after the last participant enrollment. Patients will primarily be assessed by prostate-specific antigen (PSA) progression-free survival (PFS).

Official Title
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Japanese Research for Patients With Non-metastatic Castration Resistant Prostate Cancer - Enzalutamide

Conditions
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Prostate Cancer

Intervention / Treatment
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* Drug: Enzalutamide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with histologically or cytologically confirmed prostate cancer Patients with history of radical prostatectomy or radiation therapy for radical treatment Patients who receive continuous androgen deprivation therapy using both gonadotropin-releasing hormone (GnRH) agonist and antagonist, or using surgical castration Patients with serum testosterone 1.73 nmol/L (0.50 ng/dL) or less Patients with history of bicalutamide or flutamide at any time after first recurrence confirmed since radical treatment completed Patients with 3 increased PSA test results which measured consecutively at least one week apart during androgen deprivation therapy Patients with serum PSA 1 micrograms/L (1 ng/mL) or more Patients with no confirmed remote metastasis after diagnosis of prostate cancer (excluding lymph nodes metastasis with a minor axis of less than 15 mm which considered to be nonmeasurable in the Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1) Patients with asymptomatic prostate cancer Patients with the Eastern Cooperative Oncology Group (ECOG) performance status 0-1 Patients with life expectancy of at least 12 months Patients who have signed written informed consent to participate in this study Exclusion Criteria: Patients with history of any chemotherapy (including estramustine phosphate sodium hydrate (JAN)) or treatment with enzalutamide or abiraterone acetate Patients with history of steroid usage as treatment for prostate cancer Patients with history of 5-alpha-reductase inhibitor, estrogen or steroidal antiandrogen within past 4 weeks prior to initial administration of enzalutamide Patients with history of malignant tumor other than prostate cancer within past 3 years 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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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Enzalutamide Group<br> | Drug: Enzalutamide<br>* All patients will receive enzalutamide 160 mg (four 40 mg capsules) orally once daily. The treatment will be started at Visit 0 within one week after enrollment. Visit 1 is at 2 weeks after the treatment started; clinical assessments are conducted on adverse events and the Japanese version of the Functional Assessment of Cancer Therapy-Prostate (FACT-P) scales. Patients who are considered to be adequate by the investigator can continue the treatment with 12-week cycle visit (counted from initial dose) until patients meet withdrawal criteria. Patients will be followed up at 2 and 3 years after enrollment and at 3 years after the last participant enrollment.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PSA-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. | 6 years | 

Secondary 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. | 6 years | 
| 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. | 6 years | 
| Metastasis free survival (MFS) | MFS is defined as time from date of initial dose until the date of first metastasis which confirmed by computed tomography (CT) and bone scintigraphy. | 6 years | 
| 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). | 6 years | 
| PSA response rate | PSA response rate is defined as ratio of patients who have an decrease in PSA of >= 50% above baseline, compared to PSA levels at week 2, every 12 weeks for up to 5 years after initial dose. | At week 2, and every 12 weeks for up to 6 years after initial dose | 
| Time to first use of chemotherapy (TFC) | TFC is defined as time from date of initial dose until the date of first additional chemotherapy started for prostate cancer. | 6 years | 
| QOL assessment using Japanese version of the FACT-P scales | Quality of life (QOL) is assessed on both total scores and each domain scores using Japanese version of the Functional Assessment of Cancer Therapy-Prostate (FACT-P) scales at baseline, week 2, week 60, withdrawal of treatment and at the end of treatment for up to 5 years. | Baseline, week 2, week 60, at withdrawal of treatment and at end of treatment for up to 6 years | 
| Medication adherence (dosage) | Medication adherence is assessed in dosage of enzalutamide. | 6 years | 
| Medication adherence (duration) | Medication adherence is assessed in duration of enzalutamide. | 6 years | 
| Medication adherence (ratio) | Medication adherence is assessed in dosage rate of enzalutamide which is classfied into 3 categories: 1) >=80%, 2) >= 50% to < 80%, and 3) < 50%. | 6 years | 
| Safety assessment on the incidence and severity of adverse events using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 |  | 6 years |