Metastatic castration-resistant prostate cancer MedDRA version: 21.1 Level: LLT Classification code 10076506 Term: Castration-resistant prostate cancer System Organ Class: 100000004864
Conditions
Interventions
Product Name: ODM-208
Pharmaceutical Form: Tablet
INN or Proposed INN: ODM-208
Other descriptive name: ODM-208
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 25-
Sponsors
Orion Corporation Orion Pharma
Eligibility
Sex/Gender
Male
Inclusion criteria
Inclusion criteria: 1. Written informed consent (IC) obtained. 2. Males aged = 18 years. 3. Life expectancy > 3 months. 4. ECOG performance status 0-1. 5. For Part 1/Phase1: Histologically confirmed adenocarcinoma of the prostate without neuroendocrine differentiation or small cell features. For Part 2/Phase 2: Histologically confirmed adenocarcinoma of the prostate without pure small cell features. 6. Metastatic disease documented either by a positive bone scan, CT, PET/CT or MRI scan. 7.Castration-resistant prostate cancer with serum testosterone =1 ng/ml (For Part2/Phase 2), >=2 ng/ml (for Part 1/Phase1). ? soft tissue disease progression as defined by RECIST 1.1 criteria. ? bone disease progression as defined by PCWG3 criteria. 13. Adequate marrow, liver and kidney function. ? haemoglobin = 10 g/dl (in absence of blood transfusion within 7 days of value obtained) ? absolute neutrophil count (ANC) = 1500/µl (1.5 x 10?/l) ? platelet count = 100 000/µl (100 x 10?/l ) ? aspartate aminotransferase (AST) and alanine aminotransferase (ALT) = 3 x upper limit of normal (ULN) (= 5.0 x ULN if liver metastases present) For Part 2 DDI cohort: AST and ALT = 1.5 x ULN. ? total bilirubin = 1.5 x ULN (=65 years) yes F.1.3.1 Number of subjects for this age range 102
Exclusion criteria
Exclusion criteria: 1. History of pituitary dysfunction. 2. For Part 1/Phase 1: Known brain metastases or active leptomeningeal disease. For Part 2/Phase 2: Known brain metastases. 3. Other concurrent malignancies, except adequately treated basal cell or squamous cell carcinoma of the skin. Patients who have undergone potentially curative therapy for a prior malignancy are eligible provided there is no evidence of disease for > 3 years (Part 2/Phase 2) or >=5 years (Part 1/Phase 1) and patient is deemed to be at low risk for recurrence. 4. Active or uncontrolled autoimmune disease requiring concurrent corticosteroid therapy. 5. Active infection or other medical condition that would make corticosteroid contraindicated. 6. Use of aldosterone antagonist (e.g. spironolactone, eplerenone) and phenytoin within 4 weeks prior start of the study treatment. 8. Prior radiotherapy, chemotherapy within the last 4 weeks (2 weeks for oral or weekly chemotherapy; 6 weeks for nitrosoureas and mitomycin C) prior to the start of the study treatment. Concurrent radiotherapy for palliation is allowed. 9. Part 1/Phase 1: Use of enzalutamide within 4 weeks and abiraterone acetate within 2 weeks prior to the start of study treatment. Use of other anticancer therapy (excluding GnRH) within 4 weeks prior to the start of the study treatment. Use of immune checkpoint inhibitor within 12 weeks prior to the start of the study treatment (amendment 4) Part 2/Phase 2: Use of enzalutamide and apalutamide within 3 weeks, use of darolutamide and abiraterone acetate within 2 weeks prior to the start of study treatment. Use of other anticancer therapy (excluding GnRH) within 4 weeks prior to the start of the study treatment. Use of immune checkpoint inhibitor within 12 weeks prior to the start of the study treatment. 10. For Part 1/Phase 1 only: Known gastrointestinal (GI) disease or GI procedure that may interfere with absorption of study treatment. 12. Hypotension: systolic BP 450 ms (for Part 1/Phase 1), > 470 ms (for Part 2/Phase 2), or any clinically significant abnormality in the centrally-read ECG. 19. Part 1/Phase 1 (Finland, France and UK) and Part 2/Phase 2 (France and UK): Known history of human immunodeficiency virus (HIV), or acute or chronic hepatitis B or hepatitis C disease. Part 2/Phase 2 (US and Finland): Patients with HIV on established antiretroviral therapy (ART) less than four weeks and/or an HIV viral load more than 400 copies/mL prior to enrolment (added in Amendment 8). 21. Participation in another interventional clinical trial with an investigational agent with an investigational agent or any concurrent treatment with any investigational drug 4 weeks (immune checkpoint inhibitors 12 weeks) prior to the start of the study treatment. 22. Part 2/Phase 2 (excluding DDI cohort): Systemic use of the following medications within 2 we
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Part 1/Phase1: Primary objectives are: - to evaluate the safety and tolerability of ODM-208 in patients with metastatic castration-resistant prostate cancer (mCRPC), - to define the maximum tolerated dose (MTD) and dose limiting toxicities (DLTs) of ODM-208, if possible, - to define the recommended dose of ODM-208 for Part 2 of the study. Part 2/Phase2: Primary objectives are: - to further evaluate the safety and tolerability of ODM-208, - to further evaluate antitumour activity of ODM-208 in mCRPC patients with and without mutated androgen receptor (AR) ligand-binding domain (LBD) who have progressed after novel AR targeted therapy and taxane-based chemotherapy - to evaluate potential for DDI due to time-independent inhibition of CYP3A4 by ODM-208 (added in Protocol Amendment 13);Secondary Objective: Part 1/Phase1: Secondary objectives are: - to characterise the pharmacokinetics (PK) of ODM-208 after single and repeated administration, - to evaluate dosing schedule of ODM-208. - to evaluate preliminary antitumour activity of ODM-208. Part 2/Phase2: Secondary objectives are: - to evaluate different AR LBD mutations and their association with antitumour activity of ODM-208 ;Primary end point(s): - Safety: adverse events, vital signs including blood pressure, heart rate, body temperature and orthostatic test (part 1 only), 12-lead ECGs; physical exams, laboratory assessments: hematology, chemistry, urinalysis. Determined at several time-points - MTD/DLTs - Efficacy assessments: Serum total PSA, soft tissue response by CT or MRI scan, bone scan, ECOG performance score. Circulating tumour cell (CTC) response (Part 2 only) ;Timepoint(s) of evaluation of this end point: - Safety: Determined at several time-points - Efficacy assessments: Serum total PSA (every 4 weeks for 24 weeks; every 12 weeks thereafter), soft tissue response by CT or MRI scan (every 8 weeks for 24 weeks; every 12 weeks thereafter), bone scan (every 8 weeks for 24 weeks; ever | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Pharmacokinetic assessments: Multiple blood samples for PK; Plasma samples for protein binding - Metabolite screening: Multiple blood samples and urine collection - Recommended dose for further studies. - evaluate different AR LBD activating mutations and their association with antitumour activity of ODM-208. Exploratory: - Pharmacodynamic assessments: Testosterone level and other steroid hormones; - Biomarker assessments: Biomarkers in plasma may be performed on the steroid hormone samples; Germline DNA and pharmacogenomics. - to evaluate the relationship between AR-V7 splicing variant and antitumor activity of ODM-208 (Part 2/Phase 2 only) - molecular biomarkers at genomic, protein and metabolite level from plasma/serum - overall survival assessment (Part 2/Phase 2 only) ;Timepoint(s) of evaluation of this end point: - Pharmacokinetic assessments: Multiple blood samples for PK on study days 1 and 8; Plasma samples for protein binding at 2 time points on Day 8; - Metabolite screening: Multiple blood samples on study days 1 and 8; urine collection on study days 1 and 8 - Recommended dose for further studies. Exploratory: - Pharmacodynamic assessments: Testosterone level and other steroid hormones; Multiple blood samples on study days 1 and 8 - Biomarker assessments: Biomarkers in plasma may be performed on the steroid hormone samples; Germline DNA and pharmacogenomics: at pre-dose on Day 1. -OS assessment: to date of death from any cause, until end of the study | — |
Countries
Finland, France, United Kingdom, United States
Contacts
Public ContactVirpi Mononen
Orion Corporation Orion Pharma
Outcome results
None listed