Safety and Tolerability of ODM-203 in Subjects With Advanced Solid Tumours

Study Overview
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Brief Summary
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The purpose of this first-in-human study is to evaluate the safety and tolerability of escalating doses of ODM-203 in subjects with advanced solid tumours and to determine the maximum tolerated dose and dose limiting toxicities.

Detailed Description
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The safety profile of ODM-203 will be explored together with the pharmacokinetics, pharmacodynamics and tumour response to treatment with ODM-203 to recommend the dosing regimen for further clinical studies. The pharmacokinetic properties of ODM 203 will be evaluated after single and multiple dose administrations at different dose levels

Official Title
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Safety and Tolerability of Single and Repeated Doses of ODM-203: An Open-label, Non-randomised, Uncontrolled, Dose Escalation, Multicentre, First-in-Human Study in Subjects With Advanced Solid Tumours

Conditions
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Solid Tumours

Intervention / Treatment
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* Drug: ODM 203
* Drug: ODM 203


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Written informed consent Male and female subjects over 18 years of age Subjects with histologically or cytologically confirmed locally advanced or metastatic tumours. Subjects in Part 2 to have a tumour/genetic aberration. Availability of tumour sample for genetic analysis Adequate haemopoietic, hepatic and renal function Eastern Cooperative Oncology Group performance status of 0 to 1 Serum mineral levels phosphate: 2.5 mg/dl; calcium: 8.8 mg/dl; magnesium: 1.2 mg/dl; potassium: 11.7 mg/dl; sodium: 299mg/dl. Recovery from reversible adverse events of previous systemic anti-cancer therapies to baseline or grade 1 with the exception of alopecia;stable neuropathy of grade 2 induced by previous cancer treatment Life expectancy of 12 weeks or more Exclusion Criteria: Any prior anti VEGFR/FGFR treatment related AE that in the judgement of the investigator is considered severe/life threatening Subjects receiving warfarin Active central nervous system metastases not controlled by prior surgery/radiotherapy and/or low dose steroids for 4 weeks or more Subjects with current evidence of endocrine alteration of calcium-phosphate homeostasis Concomitant therapies known to increase serum phosphorus and/or calcium levels that cannot be discontinued or switched to a different therapy are not permitted within 14 days before the first dose of ODM-203. Significant cardiovascular conditions/circumstances as follows: a active or unstable cardio/cerebro-vascular disease b Uncontrolled hypertension (systolic blood pressure ≥ 150mmHg and/or diastolic blood pressure ≥ 90mg Hg with optimised antihypertensive therapy. c history of severe arrhythmia, familial arrhythmia, conduction abnormality or congenital long QT syndrome dConcomitant therapies known to prolong the QT interval and associated with a risk of Torsades de Pointes are not permitted within 7 days before the first dose of ODM 203 e Repeatable prolongation of QTcF interval ≥ 450 msec or any clinically significant abnormality in the ECG at screening in 2 out of 3 recordings f Left ventricular ejection fraction <50% at screening Subjects who received systemic anticancer treatment prior to the first dose of ODM-203 within the following timeframes: less than 28 days since the last dose of antineoplastic therapy and/or 28 days of wide field radiotherapy or 14 days of limited field radiation for palliation Major surgery or serious infection within 21 days of the first dose of ODM-203 Known gastrointestinal disease or a procedure that may affect absorption of ODM 203 Serious concurrent medical condition or psychiatric illness History and/or current evidence of ectopic mineralisation/calcification Known active or past history of other primary malignancy Female of child bearing potential Female of child bearing potential or male subject with a female partner of child bearing potential who does not agree to use effective contraception during the study and for 3 months after the last dose of ODM 203 Known hypersensitivity to the study treatment excipients Any condition which in the opinion of the investigator would impair the subject's ability to comply with the study procedures Participation in another interventional clinical trial/ concurrent treatment with any investigational drug within 4 weeks prior to the start of treatment with ODM 203

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ODM 203<br>Oral capsules given once daily dosage 50-800mg | Drug: ODM 203<br>* ODM 203<br>Drug: ODM 203<br>* ODM 203<br>|
| Experimental: ODM-203<br>Oral tablets given once daily 200-1600mg | Drug: ODM 203<br>* ODM 203<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of adverse events | Number of adverse event counts | From the date of informed consent to the date of the end of study visit estimated to be 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Frequency of responders to Response evaluation criteria in solid tumours (RECIST) | The frequency of responders according to RECIST will be evaluated by dose level. | Subjects will be followed for the duration of time in the study, expected to be an average of 6 months | 
| Eastern Cooperative Oncology Group (ECOG) Performance status | The ECOG performance status and the change from baseline will be reported by dose level. | Subjects will be followed for the duration of time in the study, expected to be an average of 6 months | 
| Area under the plasma concentration curve (AUC) | Area under the plasma concentration curve (AUC) of ODM-203 will be measured to evaluate the relationship between ODM-203 dose, plasma exposure, pharmacodynamics and safety | 0 to 24hours post dose Day 1 and Day 15 | 
| Peak plasma concentration (Cmax) | Peak plasma concentration (Cmax) of ODM-203 will be measured to evaluate the relationship between ODM-203 dose, plasma exposure, pharmacodynamics and safety | After first dose administration to 24 hours Day 1 and Day 15 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Solid tumours