Safety and Pharmacokinetics Study of ODM-201 in Castrate Resistant Prostate Cancer

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to evaluate safety, tolerability and pharmacokinetics of ODM-201 in patients with castrate resistant prostate cancer.

Official Title
-----------------
Safety and Pharmacokinetics of ODM-201 in Patients With Castrate Resistant Prostate Cancer: Open, Non-randomised, Uncontrolled, Multicentre, Multiple Dose Escalation Study With a Randomised Phase II Expansion Component

Conditions
-----------------
Prostate Cancer

Intervention / Treatment
-----------------
* Drug: ODM-201


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Written informed consent Histologically confirmed adenocarcinoma of prostate Ongoing androgen deprivation therapy with a LHRH analogue or antagonist or bilateral orchiectomy Progressive metastatic disease Adequate bone marrow, hepatic, and renal function Exclusion Criteria: Known metastases in the brain History of other malignancy within the previous 5 years Known gastrointestinal disease or procedure that affects the absorption Not able to swallow the study drug

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
Male

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ODM-201 Phase I<br> | Drug: ODM-201<br>* ODM-201 administered orally daily<br>|
| Experimental: ODM-201 Phase II Dose 1<br> | Drug: ODM-201<br>* ODM-201 administered orally daily<br>|
| Experimental: ODM-201 Phase II Dose 2<br> | Drug: ODM-201<br>* ODM-201 administered orally daily<br>|
| Experimental: ODM-201 Phase II Dose 3<br> | Drug: ODM-201<br>* ODM-201 administered orally daily<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phase 1: Number of Participants Who Experienced Dose Limiting Toxicity (DLT) | A DLT was any Grade 3 or more toxicity (by National Cancer Institute Common Terminology Criteria for Adverse Events [NCI CTCAE version 4.03]) excluding less than Grade 4 neutropenia or thrombocytopenia, hematological toxicity lasting less than 7 days, and nausea, vomiting, diarrhea controlled with antiemetic and/or anti-diarrheal treatment. | Up to 28 days for each cohort | 
| Phase 1: Number of Dose Limiting Toxicities Used to Determine the Maximum Tolerated Dose | The MTD is defined as dose level at which 2 or more out of 6 participants experience a dose limiting toxicity (DLT) | Up to 28 days for each cohort | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phase 1 and 2: Participants With Decline of at Least 50% in Prostate-specific Antigen (PSA) in Chemotherapy-naïve and CYP17i-naïve Group | Number of participants with greater than or equal to 50% decrease in serum PSA from baseline at 12 weeks in group of participants who were naïve to both chemotherapy and CYP17 inhibitor | 3 months | 
| Phase 1 and 2: Participants With Decline of at Least 50% in Prostate-specific Antigen (PSA) in Post-chemotherapy and CYP17i-naïve Group | Number of participants with greater than or equal to 50% decrease in serum PSA from baseline at 12 weeks in group of participants previously treated with chemotherapy but not CYP17 inhibitor | 3 months | 
| Phase 1 and 2: Participants With Decline of at Least 50% in Prostate-specific Antigen (PSA) in Post-CYP17i Group | Number of participants with greater than or equal to 50% decrease in serum PSA from baseline at 12 weeks in group of participants previously treated with CYP17 inhibitor | 3 months | 
| Phase 1 and 2: Participants With RECIST Response in Soft Tissue in Chemotherapy-naïve and CYP17i-naïve Group | Number of participants with overall complete response (CR), partial response (PR) or stable (SD) soft tissue disease according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1) in chest, abdomen, and pelvic CT or MRI scans. | 3 months | 
| Phase 1 and 2: Participants With RECIST Response in Soft Tissue in Post-chemotherapy and CYP17i-naive Group | Number of participants with overall complete response (CR), partial response (PR) or stable (SD) soft tissue disease according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1) in chest, abdomen, and pelvic CT or MRI scans. | 3 months | 
| Phase 1 and 2: Participants With RECIST Responses in Soft Tissue in Post-CYP17i Group | Number of participants with overall complete response (CR), partial response (PR) or stable (SD) soft tissue disease according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1) in chest, abdomen, and pelvic CT or MRI scans. | 3 months | 
| Phase 1 and 2: Participants With Stable Bone Disease in Chemotherapy-naïve and CYP17i-naïve Group | Number of participants with stable bone disease (no change). Radiographic bone progression was defined by the appearance of two or more new lesions on bone scan | 3 months | 
| Phase 1 and 2: Participants With Stable Bone Disease in Post-chemotherapy and CYP17i-naïve Group | Number of participants with stable bone disease (no change). Radiographic bone progression was defined by the appearance of two or more new lesions on bone scan | 3 months | 
| Phase 1 and 2: Participants With Stable Bone Disease in Post-CYP17i Group | Number of participants with stable bone disease (no change). Radiographic bone progression was defined by the appearance of two or more new lesions on bone scan | 3 months | 
| Phase 1: Area Under the Plasma-Concentration-time Curve (AUCt) of ODM-201 at Steady-state | AUC(0-8h) | Day 8 predose 0 h and 0.5, 1, 1.5, 2, 4, 6 and 8 h postdose | 
| Phase 1: Maximum Plasma Concentration (Cmax) of ODM-201 at Steady-state |  | Day 8 predose 0 h and 0.5, 1, 1.5, 2, 4, 6 and 8 h postdose | 
| Phase 1: Time to Reach the Maximum Observed Concentration (Tmax) of ODM-201 at Day 1 |  | 1 day | 
| Phase 1: Area Under the Plasma-Concentration-time Curve (AUCt) of Major Metabolite ORM-15341 at Steady-state | AUC(0-8h) | Day 8 predose 0 h and 0.5, 1, 1.5, 2, 4, 6 and 8 h postdose | 
| Phase 1: Maximum Plasma Concentration (Cmax) of Major Metabolite ORM-15341 at Steady-state |  | Day 8 predose 0 h and 0.5, 1, 1.5, 2, 4, 6 and 8 h postdose | 
| Phase 1: Time to Reach the Maximum Observed Concentration (Tmax) of Major Metabolite ORM-15341 at Day 1 |  | 1 day |