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Safety and pharmacokinetics of odm-208 in patients with metastatic castration-resistant prostate cancer
EU CTIS ID: 2024-517439-39-00
What this study is testing
Part 1/Phase 1: 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/Phase 2: 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-dependent inhibition of CYP3A4 by ODM-208 (added in Amendment 13).
- Phase I and Phase II (Integrated)- First administration to humans
A plain-language read of the study's public EU CTIS listing. The study team confirms the details.
Who can take part
You may be able to join if
- Written informed consent (IC) obtained.
- 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).
- [Obsolete inclusion criterion removed in Amendment 7.]
- 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/Phase1). - soft tissue disease progression as defined by RECIST 1.1 criteria. - bone disease progression as defined by PCWG3 criteria.
- 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 10⁹/l) - platelet count ≥ 100 000/μl (100 x 10⁹/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 (< 3 ULN if Gilbert's syndrome); \ For Part 2 . DDI cohort: total bilirubin ≤ ULN -albumin ≥ 3.0 g/dl; For Part 2 DDI cohort: albumin ≥ 3.2 g/dl - creatinine clearance ≥ 60 ml/min using serum creatinine.
- Obsolete inclusion criteria removed in Amendment 12.
You likely can't join if
- History of pituitary dysfunction.
- 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.
- 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).
- 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.
- 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).
- 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.
See the full eligibility criteria
Who can join
- Written informed consent (IC) obtained.
- 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).
- [Obsolete inclusion criterion removed in Amendment 7.]
- 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/Phase1). - soft tissue disease progression as defined by RECIST 1.1 criteria. - bone disease progression as defined by PCWG3 criteria.
- 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 10⁹/l) - platelet count ≥ 100 000/μl (100 x 10⁹/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 (< 3 ULN if Gilbert's syndrome); \ For Part 2 . DDI cohort: total bilirubin ≤ ULN -albumin ≥ 3.0 g/dl; For Part 2 DDI cohort: albumin ≥ 3.2 g/dl - creatinine clearance ≥ 60 ml/min using serum creatinine.
- Obsolete inclusion criteria removed in Amendment 12.
- Males aged ≥ 18 years.
- Life expectancy > 3 months.
- ECOG performance status 0-1.
- 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.
- Metastatic disease documented either by a positive bone scan, CT, PET/CT or MRI scan.
- Castration-resistant prostate cancer with serum testosterone < 50ng/dl (< 0.5 ng/ml,< 1.7 nmol/l).
- Patients must maintain ongoing androgen deprivation therapy with a gonadotropinreleasing hormone (GnRH) analogue (agonist oantagonist), or have had bilateral orchiectomy.
- 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.
What rules you out
- History of pituitary dysfunction.
- 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.
- 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).
- 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.
- 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).
- 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.
- Part 2/Phase 2 (excluding DDI cohort): Systemic use of the following medications within 2 weeks prior to the start of study treatment (added in Amendment 8): -Strong CYP3A4 inducers: E.g. avasimibe, carbamazepine, lumacaftor, phenobarbital, rifampicin, rifapentine, St John's Wort -P-gp inhibitors: erythromycin, clarithromycin, rifampicin, ketoconazole, itraconazole, posaconazole, artesunate-pyronaridine, ritonavir, indinavir, nelfinavir, atazanavir, glecaprevir-pibrentasvir, simeprevir, ledipasvirsofosbuvir, verapamil, diltiazem, dronedarone, propafenone, quinidine, cyclosporine, valspodar, milk thistle (Silybum marianum) For Part 2 DDI cohort: Systemic use of the following medications within 3 weeks prior to the start of study treatment (added in Amendment 13): •moderate and strong CYP3A4 inducers and inhibitors (the duration of the wash-out should be discussed with the Sponsor) •mild CYP3A4 inducers and inhibitors •P-gp inhibitors: erythromycin, clarithromycin, rifampicin, ketoconazole, itraconazole, posaconazole, artesunate-pyronaridine, ritonavir, indinavir, nelfinavir, atazanavir, glecaprevir-pibrentasvir, simeprevir, ledipasvirsofosbuvir, verapamil, diltiazem, dronedarone, propafenone, quinidine, cyclosporine, valspodar, milk thistle (Silybum marianum).
- For Part 2 DDI cohort: Use of opioids or benzodiazepines within 2 weeks prior to the start of the study treatment.
- For Part 2 DDI cohort: Known sensitivity to midazolam or other anxiolytics, or concern for inability to tolerate 1 mg of oral midazolam.
- For Part 1/Phase 1: Known brain metastases or active leptomeningeal disease. For Part 2/Phase 2: Known brain metastases.
- 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.
- Active or uncontrolled autoimmune disease requiring concurrent corticosteroid therapy.
- Active infection or other medical condition that would make corticosteroid contraindicated.
- Use of aldosterone antagonist (e.g. spironolactone, eplerenone) and phenytoin within 4 weeks prior start of the study treatment.
- 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.
- 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.
- For Part 1/Phase 1 only: Known gastrointestinal (GI) disease or GI procedure that may interfere with absorption of study treatment.
The study team makes the final eligibility decision.
Where it's taking place
- United States
- United Kingdom
Questions & answers
Do participants get paid in this trial?
This listing doesn't specify compensation. Many trials still reimburse travel or offer a stipend, so it's worth asking the study team when you connect.
Is it free to join, and do I need insurance?
Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part - confirm specifics with the study team.
How long does this study last?
The listing doesn't state an exact length. The study team walks you through the schedule and number of visits before you decide to enroll.
Who can join this trial?
This study is enrolling male, 65+ years, 18-64 years. The study team makes the final eligibility decision.
Where is this trial taking place?
Study sites include United States; United Kingdom. Enter your location above to see the nearest site and check your eligibility.
Explore other conditions
BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from EU CTIS; the study team decides eligibility.