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

January 14, 2020 updated by: Orion Corporation, Orion Pharma

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

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

Study Type

Interventional

Enrollment (Actual)

84

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

      • Copenhagen, Denmark
        • Finsen Centre
      • Helsinki, Finland, 00029
        • Helsinki University Central Hospital, Department of Oncology
      • Bordeaux, France, 33000
        • Institut Bergonie
      • Villejuif, France, 94805
        • Gustave Roussy Oncology Institute
      • Milan, Italy, 20141
        • European Institute of Oncology
      • Barcelona, Spain, 08035
        • Vall D'Hebron University Hospital
      • London, United Kingdom, W1G6AD
        • Sarah Cannon Research Institute
      • London, United Kingdom, WC1E6DD
        • UCL Cancer Institute

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: ODM 203
Oral capsules given once daily dosage 50-800mg
ODM 203
Experimental: ODM-203
Oral tablets given once daily 200-1600mg
ODM 203

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of adverse events
Time Frame: From the date of informed consent to the date of the end of study visit estimated to be 6 months
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)
Time Frame: Subjects will be followed for the duration of time in the study, expected to be an average of 6 months
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
Time Frame: Subjects will be followed for the duration of time in the study, expected to be an average of 6 months
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)
Time Frame: 0 to 24hours post dose Day 1 and Day 15
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)
Time Frame: After first dose administration to 24 hours Day 1 and Day 15
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Principal Investigator: Petri Bono, MD, Helsinki University Central Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 18, 2014

Primary Completion (Actual)

May 1, 2019

Study Completion (Actual)

May 1, 2019

Study Registration Dates

First Submitted

September 19, 2014

First Submitted That Met QC Criteria

October 9, 2014

First Posted (Estimate)

October 15, 2014

Study Record Updates

Last Update Posted (Actual)

January 18, 2020

Last Update Submitted That Met QC Criteria

January 14, 2020

Last Verified

January 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 3113001

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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