SAFETY AND PHARMACOKINETICS OF ODM-208 IN PATIENTS WITH METASTATIC CASTRATION-RESISTANT PROSTATE CANCER
- Conditions
- Metastatic castration-resistant prostate cancerMedDRA version: 21.1Level: LLTClassification code 10076506Term: Castration-resistant prostate cancerSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2017-002534-23-GB
- Lead Sponsor
- Orion Corporation Orion Pharma
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Male
- Target Recruitment
- 112
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/Phase 1: 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 < 50 ng/dl (< 0.5 ng/ml,< 1.7 nmol/l).
8. Patients must maintain ongoing androgen deprivation therapy with a gonadotropinreleasing hormone (GnRH) analogue (agonist or antagonist), or have had bilateral orchiectomy.
9. For Part 1/Phase 1: Treatment with at least 1 line of chemotherapy or ineligibility for chemotherapy. For Part 2/Phase 2: Treatment with at least 1 line of taxane-based chemotherapy in castration-sensitive prostate cancer (CSPC) or in CRPC.
10. Treatment of at least 1 line of novel AR targeted hormonal therapy in CSPC or in CRPC for a minimum of 12 weeks (e.g. abiraterone, enzalutamide, darolutamide, apalutamide).
11. [Obsolete inclusion criterion removed in Amendment 7.]
12. Documented disease progression by one or more of the following criteria:
- PSA progression defined by a minimum of 2 elevated PSA levels with an interval of at least 1 week between the measurements. The PSA value at the screening visit should be >=1 ng/ml (For Part2/Phase 2), >=2 ng/ml (for Part 1/Phase 1).
- 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)
- total bilirubin = 1.5 x ULN (< 3 ULN if Gilbert's syndrome)
- albumin = 3.0 g/dl
- creatinine = 1.5 ULN or calculated creatinine clearance = 60 ml/min/1.73 m2 for patients with creatinine levels above normal limit
17. For Part 2/Phase 2 only (added in Amendment 7): Patients with identified activating mutation in the LBD of AR in plasma ctDNA confirmed by the central testing
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 56
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 56
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 < 110 mmHg, or uncontrolled hypertension: systolic = BP 160 mmHg or diastolic = BP 90 mmHg (for Part 2/Phase 2:
95 mmHg), in 2 out of 3 recordings with optimized antihypertensive therapy.
14. Active or unstable cardio/cerebro-vascular disease, including thromboembolic events. Examples include recent (within 6 months) myocardial infarction, coronary artery bypass graft or symptomatic cerebrovascular accident or congestive heart failure (New York Heart Association class III-IV) (for Part 1/Phase 1), III-IV (for Part 2/Phase 2).
15. History or family history of long QTc syndrome. Repeatable prolongation (2 out of 3 recordings) of QTcF interval > 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. Known history of human immunodeficiency virus (HIV), hepatitis B, or hepatitis C.
21. Participation in another interventional clinical trial 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.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method