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

• Status: Completed
• Trial end date: 2019-05-01
• Target enrollment: 0
• Participant gender: All

Summary

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.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Orion Corporation, Orion Pharma

Criteria

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