Metastatic castration resistant prostate cancer (mCRPC) MedDRA version: 18.1 Level: PT Classification code 10036909 Term: Prostate cancer metastatic System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 18.1 Level: LLT Classification code 10036916 Term: Prostate cancer stage D
Conditions
Interventions
Product Name: ODM-204 50 mg
Product Code: ODM-204 50 mg
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: ODM-204
Current Sponsor
Sponsors
Orion Corporation Orion Pharma
Eligibility
Sex/Gender
Male
Inclusion criteria
Inclusion criteria: 1. Written informed consent (IC) obtained. 2. Male aged = 18 years. 3. Histologically or cytologically confirmed adenocarcinoma of prostate. 4. Castrate level of serum testosterone ( 3.0 g/dl. 11. Serum potassium = 3.5 mmol/l. 12. Able to swallow study treatments and comply with study requirements. 13. Acceptable and regular bowel movements in the judgement of the investigator without any acute, subacute or chronic gastrointestinal (GI) obstruction or other GI disorder or procedure which may interfere significantly with absorption of study treatment. 14. Sexually active subjects, unless surgically sterile, must agree to use condoms and an additional effective contraception method during the study treatment and for 3 months after the end of the study treatment. 15. Patients on systemic glucocorticoids for the treatment of prostate cancer or control of symptoms must have documented PSA progression by PCWG2 criteria prior start of study treatment. Patients with confirmed PSA progression while on systemic corticosteroids other than Prednison® are required to switch to Prednison® 5 mg (once or twice a day depending on the previous glucocorticoid dose) prior the start of study treatment, but PSA progression does not have to be reconfirmed. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 45 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 50
Exclusion criteria
Exclusion criteria: 1. History of pituitary or adrenal dysfunction. 2. Known brain metastases. 3. Active infection or other medical condition that would make prednisone (corticosteroid) contraindicated. 4. Poorly controlled diabetes as judged by the investigator. 5. Prior therapy with any investigational CYP17A1i (e.g. TAK-700, TOK-001) or any investigational second-generation AR inhibitors (e.g. ARN-509, ODM-201). 6. Depending upon patient’s prior treatment, the following apply: - prior chemotherapy: not more than 2 prior chemotherapy treatments are allowed; chemotherapy is not allowed within 4 weeks before the start of the study treatment - prior abiraterone therapy must have been stopped at minimum 2 weeks before the start of the study treatment - prior second-generation AR inhibitor therapy must have been stopped at minimum 4 weeks before the start of the study treatment. 7. Use of first-generation AR inhibitor within 4 weeks (within 6 weeks for bicalutamide and nilutamide) before start of the study treatment. 8. Systemic therapy with ketoconazole, or any other azole drug (e.g. fluconazole, itraconazole) within 4 weeks before the start of the study treatment. 9. Use of estrogens, cyproterone acetate, 5-a reductase inhibitors (finasteride, dutasteride) or biologic treatment within 4 weeks before the start of the study treatment. Prior radiotherapy within 4 weeks or palliative radiotherapy within 2 weeks before start of study treatment. 10. Any acute toxicities due to prior chemotherapy and/or radiotherapy that have not resolved to a NCI CTCAE (version 4.03) grade of = 1. Chemotherapy induced alopecia and grade 2 peripheral neuropathy is allowed. 11. Initiation of an osteoclast-targeted therapy (bisphosphonate or denosumab) within 4 weeks before the start of the study treatment. Patients on a stable dose of osteoclast-targeted therapy for at least 4 weeks before the start of the study treatment can continue the treatment during the study. 12. Participation in another interventional clinical trial and any concurrent treatment with any other investigational drug except those mentioned in exclusion criterion 7 within 4 weeks before start of the study treatment. 13. Uncontrolled hypertension ? systolic BP = 160 mmHg or ? diastolic BP = 95 mmHg. Subjects with history of hypertension can be included, provided that BP is controlled by anti-hypertensive therapy. 14. Clinically significant heart disease as judged by the investigator, e.g. congestive heart failure New York Heart Association (NYHA) class = 3, myocardial infarction, arterial thrombotic and embolic events in the past 6 months, or unstable angina. 15. Prolonged QTc interval as evidenced by: ? history or family history of long QTc syndrome ? prolonged QT interval corrected by the Fridericia correction formula (QTcF) > 450 ms on the centrally-read ECG at screening (2 of the measurements at screening > 450 ms). 16. Major surgery within 4 weeks before the start of the study treatment. 17. History of signi
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate safety and tolerability of ODM-204 including dose limiting toxicities (DLTs) and the maximum tolerated dose (MTD), if possible ; Primary end point(s): Achieving a maximum tolerated dose (MTD) or dose limiting toxicity (DLT). ; Secondary Objective: To evaluate: - PK profile of ODM-204 and its metabolites ORM-24178, ORM-25367, ORM-26343 and possible other metabolites after a single and repeated administration in fed and fasted condition at different dose levels - PD profile of ODM-204 (including hormone and circulating tumour cell [CTC] measurements) - preliminary antitumour activity of ODM-204 in different populations to be studied (see section 4.1) according to the following criteria: PSA response; response in bone and soft tissue; time on treatment; the dose of ODM-204 for further clinical studies; long term safety and tolerability of ODM-204; time to PSA and radiological progression ; Timepoint(s) of evaluation of this end point: MTD is the dose level at which 2 or more out of 6 subjects in a cohort experience a DLT and those subjects who have received study treatment for 28 days or who had to discontinue study treatment earlier than 28 days because of DLT. DLT is defined as any of the following toxicities with grade: - = 3 toxicity, excluding haematological toxicities, nausea, vomiting and diarrhoea - = 3 nausea, vomiting and diarrhoea uncontrolled with antiemetic and/or antidiarrheal therapy - = 3 haematological toxicity lasting for = 7 days - = 4 thrombocytopenia and neutropenia - Other laboratory values of = grade 3 which are judged clinically significant by the investigator - any other toxicity which in the judgement of the investigator and/o | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): PK profile; hormone assessment and circulating tumour cells (CTC). For preliminary antitumour activity a serum total PSA concentration (PSA response and progression) and soft tissue response and progression will be evaluated (chest, abdomen and pelvic CT or MRI will be performed); bone response and progression will be evaluated by a radionuclide bone scan. ; Timepoint(s) of evaluation of this end point: - Serum total PSA concentration will be determined every 4 weeks until 24 weeks and every 12 weeks thereafter. In case of PSA progression a confirmatory test should be obtained 3-4 weeks later. - Chest, abdomen and pelvic CT or MRI will be performed at screening, week 12 and every 12 weeks thereafter. - Radionuclide bone scan will be performed at screening, week 12 and every 12 weeks thereafter, except for subjects with no bone metastasis or bone pain at week 12 the scan should be performed every 24 weeks. In case of bone progression, a confirmatory scan should be performed in 6 weeks. | — |
Countries
Finland, Latvia, United Kingdom
Contacts
Public ContactVirpi Mononen
Orion Corporation Orion Pharma
Outcome results
None listed