A Phase 3 Comparative Study of TAP-144-SR(6M) in Prostate Cancer Patients Previously Treated With Hormonal Therapy

Study Overview
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Brief Summary
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The purpose of this study is to evaluate hormone dynamics, pharmacokinetics, safety, and efficacy of TAP-144-SR(6M) against TAP-144-SR(3M) in prostate cancer patients previously treated with hormonal therapy.

Official Title
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A Phase 3, Multi-center, Randomized, Open-label, Parallel-group, Comparative Study of TAP-144-SR (3M) to Evaluate Hormone Dynamics, Pharmacokinetics, Safety and Efficacy of TAP-144-SR (6M) 22.5 mg Subcutaneous Injection for 48 Weeks in Prostate Cancer Patients Previously Treated With Hormonal Therapy

Conditions
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Prostate Cancer

Intervention / Treatment
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* Drug: TAP-144-SR(6M)
* Drug: TAP-144-SR(3M)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The participant has histopathologically confirmed prostate cancer in Japanese. The participant has prostate cancer in the clinical stages of T1b-T4, N-any and M-any by TNM classification on clinical diagnosis at the time of diagnosis. The participant has ECOG performance status of grades 0, 1, or 2 at screening. The participant with PSA level which has not increased 25 % or greater and 2 ng/mL or more from the nadir at the measurement points 4 weeks or longer apart within the screening period of 12 weeks. Patients who receive the marketed product for 3 months (LEUPLIN SR FOR INJECTION KIT 11.25) at screening Patients who have received the marketed products, TAP-144-SR (1M) and TAP-144-SR (3M), for 24-96 weeks in total at the scheduled starting date of the study drug, but not including administration period treated as neoadjuvant therapy for prostatectomy and/or radiation therapy Patients who have continued the nonsteroidal antiandrogen for longer than 12 weeks at the scheduled starting date of the study drug, if a nonsteroidal antiandrogen is concomitantly administered The participant with a serum testosterone level at screening < 100ng/dL The participant meets the following criteria of renal, bone-marrow and hepatic functions on the laboratory test results at screening: （1） Renal function: serum creatinine level< 1.5 times the upper limit of normal (ULN) （2） Bone-marrow function: white blood count ≥ 3,500/ mm3, platelet count ≥ 100,000/L, hemoglobin ≥ 10.0g/dL （3） Hepatic function: AST(GOT), ALT(GPT), ALP and total bilirubin ≤ 2.5 times the ULN 10. The participant's life expectancy is at least 24 months at informed consent. Exclusion Criteria: The participant has active multiple primary cancers, (synchronous multiple primary cancer or metachronous multiple primary cancer with the disease-free survival ≤ 5 years) The participant has received surgical castration. The participant has ever received LHRH agonists other than commercially available 1-month or 3-month depot of leuprolide acetate. The participant has ever received LHRH antagonists. Patients who have previously received estrogen preparations or corticosteroids for prostate cancer Patients who have previously received chemotherapy for prostate cancer Patients who are receiving or received the marketed product for 3 months (LEUPLIN SR FOR INJECTION KIT 11.25) or the marketed products for 1 month (LEUPLIN FOR INJECTION 3.75 and KIT 3.75) as an adjuvant therapy after prostatectomy and/or radiotherapy Patients who are receiving or received the marketed product for 3 months (LEUPLIN SR FOR INJECTION KIT 11.25) for intermittent androgen deprivation therapy Patients who received the following drugs within 24 weeks (168 days) after starting the study drug: Steroidal antiandrogens, type II 5α-reductase inhibitors The participant received any of the following within 16 weeks (112 days) prior to study enrollment: （1） Radiotherapy. As for I-125 brachytherapy, within 35 weeks (245 days) prior to study enrollment. （2） Prostatectomy （3） Experimental therapy including high-intensity focused ultrasound therapy (HIFU), immunotherapy, and gene therapy 11. Patients who received the following drugs within 4 weeks (28 days) before starting the study drug: Testosterones, ketoconazole（except for external preparations）, spironolactone, corticosteroids (excluding their inhalants and external preparations), and Chinese medicines and dietary supplements containing saw palmetto 12. Patients whose QTcF interval exceeded 460 msec on the 12-lead electrocardiogram at screening 13. The participant has a history of hypersensitivity to synthetic LHRH, LHRH derivative or any component of the study drug. 14. The participant has central nervous system metastasis which requires treatment or which is symptomatic. 15. The participant already has a history or has a complication or may have renal disorder caused by spinal cord compression or ureteric obstruction. 16. The participant has a history of serious drug allergic reaction/hypersensitivity 17. The participant has a history of, or has been diagnosed with thromboembolism including myocardial infarction, cerebral infarction, venous thrombosis, and pulmonary embolism, or cardiac failure

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 85 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TAP-144-SR(6M)<br>TAP-144-SR(6M) 22.5 mg, injection, treatment interval 24 weeks for up to 48 weeks. | Drug: TAP-144-SR(6M)<br> <br> |
| Active Comparator: TAP-144-SR(3M)<br>TAP-144-SR(3M) 11.25 mg, injection, treatment interval 12 weeks for up to 48 weeks. | Drug: TAP-144-SR(3M)<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Rate of Suppression of Serum Testosterone to Castrate Level | Comparison of the proportion of patients maintained at castration level (≤100 ng/dL) | From the start of study drug administration through Week 48 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time Course of Changes in Serum Testosterone |  | From baseline to Week 48 | 
| Time Course of Changes in Serum Luteinizing Hormone (LH) |  | From baseline to Week 48 | 
| Time Course of Changes in Serum Follicle-stimulating Hormone (FSH) |  | From baseline to Week 48 | 
| Time Course of Change Rate in Serum PSA (FAS) | Evaluation according to the Criteria for therapeutic effect from the General Rule for Clinical Pathological Studies on Prostate Cancer, 4th edition (determination of therapeutic effect by prostate-specific antigen [PSA]) | From baseline to Week 48 | 
| The Maximum Rate of Change in PSA Suppression (FAS) | Evaluation according to the Criteria for therapeutic effect from the General Rule for Clinical Pathological Studies on Prostate Cancer, 4th edition (determination of therapeutic effect by PSA) | From baseline to Week 48 | 
| Percentage of Participants With Progression by PSA (FAS) | Evaluation according to the Criteria for therapeutic effect from the General Rule for Clinical Pathological Studies on Prostate Cancer, 4th edition (determination of therapeutic effect by PSA) | From baseline to Week 48 | 
| Soft Tissue Response | Assessment in accordance with the criteria for therapeutic effect from the General Rule for Clinical Pathological Studies on Prostate Cancer, 4th edition. Soft tissue response was evaluated in accordance with the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by CT or MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. | At week 48 | 
| Bone Lesion Response | Partially revised assessment based on the criteria for therapeutic effect from the General Rule for Clinical and Pathological Studies on Prostate Canter, 4th edition. Response is measured using bone scintigraphy. Increase in new (2 or more) bone lesion is considered as progression | At Week 48 | 
| Serum Unchanged TAP-144 Level |  | From baseline to Week 48 | 
| 12-lead ECG |  | At 1 hour, week 24, and week 48 after administration |