Phase 1 Study of Abiraterone Acetate in Castration-resistant Prostate Cancer

Study Overview
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Brief Summary
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The purpose of this study is to assess pharmacodynamics and safety of JNJ-212082 in order to select the recommended dose of JNJ-212082 for patients with castration resistant prostate cancer.

Detailed Description
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This study is a multicenter (more than one site), open-label (both physician and patient know the name of the study drug), dose-escalation study in chemotherapy-naive patients with castration- resistant prostate cancer (CRPC) to evaluate the pharmacodynamics (the study of the action or effects of drugs on living organisms), safety, pharmacokinetics (how drugs are absorbed in the body, how they are distributed within the body and how they are removed from the body over time) and preliminary effectiveness of JNJ-212082. The dose of the study will be escalated from 250 mg (cohort 1), 500 mg (cohort 2), to 1000 mg (cohort 3). Six to twelve patients within each 250 mg, 500 mg or 1000 mg cohort will be orally administered drug once per day. Comprising 28 days for each 1 cycle, the administration will be continued up to discontinuation for any reasons such as progression of the disease or up to the transition to extension study (Protocol number: JNJ-212082-JPN-203) which will be separately planned. In addition, 5 mg of prednisolone will be orally administered twice per day since Day 8. On receiving notification of the confirmation of safety of 500 mg of the drug, patients of cohort 1 who are currently on continuous administration can receive increment 500 mg per day starting from the next cycle (If the dose escalation would not be appropriate due to safety reasons, the patients will continue the original dose). Furthermore, on receiving notification of the confirmation of safety of 1000 mg, patients of previous cohorts who are currently on continuous administration can receive increment 1000 mg per day as well from the next cycles (If the dose escalation would not be appropriate due to safety reasons, the patients will continue the original dose). JNJ-212082 will be orally administered once per day. Comprising 28 days for each 1 cycle, the administration will be continued up to discontinuation for any reasons such as progression of the disease or up to the transition to extension study. The drug will be administered at least 1 hour prior to meal or 2 hours after meal. The daily dose of the drug is defined as 250 mg, 500 mg or 1000 mg. In addition, 5 mg of prednisolone (marketed) will be orally administered twice per day since Day 8.

Official Title
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Phase 1 Study of JNJ-212082 (Abiraterone Acetate) in Patients With Castration-Resistant Prostate Cancer

Conditions
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Prostatic Neoplasms

Intervention / Treatment
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* Drug: JNJ-212082


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically or cytologically confirmed adenocarcinoma of the prostate, but not with neuroendocrine differentiation or of small cell histology No Prior cytotoxic chemotherapy (including estramustine) for the treatment of prostate cancer Surgically or medically castrated, with testosterone levels of < 0.5 ng/mL PSA level of at least 2 ng/ml at Screening PSA progression according to PCWG2 eligibility criteria or objective progression by RECIST criteria for patients with measurable disease after androgen deprivation Exclusion Criteria: Surgery or local prostatic intervention within 4 weeks of the first dose. In addition, any clinically relevant sequelae from the surgery have not resolved prior to initial treatment Radiotherapy, or immunotherapy within 4 weeks, or single fraction of palliative radiotherapy within 2 weeks of administration prior to initial treatment Known brain metastasis Uncontrolled hypertension (systolic BP greater than 160 mmHg or diastolic BP greater than 95 mmHg) Active or symptomatic viral hepatitis or chronic liver disease

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 99 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: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 001<br>JNJ-212082 250 mg 500 mg or 1000 mg once daily up to discontinuation for any reasons such as progression of the disease or up to the transition to extension study. | Drug: JNJ-212082<br>* 250 mg, 500 mg or 1000 mg once daily up to discontinuation for any reasons such as progression of the disease or up to the transition to extension study.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The pharmacodynamics (serum concentrations of corticosterone, testosterone, DHEA-S, 11-deoxycorticosterone) |  | At Days 1, 2, and 8 of Cycle 1 | 
| The number of patients reporting adverse events as a measure of safety |  | 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma concentrations of abiraterone acetate and abiraterone |  | 4 weeks | 
| Rates of decrease of prostate specific antigen (PSA)>50% (criteria of PCWG2 - Prostate Cancer Clinical Trials Working Group) |  | Maximum 52 weeks | 
| Tumor regression in patients with measurable lesions (RECIST - Response evaluation criteria in solid tumors) |  | Maximum 52 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Castration-resistant prostate cancer, Abiraterone acetate, JNJ-212082