Castration resistant prostate cancer with bone metastases. MedDRA version: 20.0 Level: PT Classification code 10062904 Term: Hormone-refractory prostate cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Name: Oncocort
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: PEG-liposomal dexamethasone sodium phosphate
CAS Number: 125-02-0
Sponsors
Enceladus Pharmaceuticals BV
Eligibility
Sex/Gender
Male
Inclusion criteria
Inclusion criteria: 1. Adult patients with mCRPC and one or more metastases in the bone, confirmed by bone scintigraphy, MRI or CT-scan within 6 weeks before first dosage; 2. Able to participate, and willing to give written informed consent and to comply with the study restrictions; 3. Body mass index (BMI) of 18 kg/m2 or higher (inclusive) and a minimum weight of 50 kg; 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 10 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Concomitant disease or condition that could interfere with, or for which the treatment might interfere with, the conduct of the study, or that would, in the opinion of the investigator, pose an unacceptable risk to the subject in this study. 2. Contraindication for glucocorticoids as judged by investigator 3. Use of systemic glucocorticosteroids within 4 weeks before first dosage, with exception of topical and inhalation steroids. 4. Any confirmed and clinically significant allergic reactions (urticaria or anaphylaxis, non-active hay fever is acceptable). Allergy or hypersensitivity against any drug, including any component of the study drug, biologic therapy or IV radiocontrast agent. 5. Clinically significant abnormalities, as judged by the investigator, following a detailed medical history, a physical examination including vital signs, 12-lead ECG and laboratory test results (including hepatic and renal panels, complete blood count, chemistry panel and urinalysis). In the case of uncertain or questionable results, tests performed during screening may be repeated before randomization to confirm eligibility or judged to be clinically irrelevant. 6. History or symptoms of any significant disease including (but not limited to), neurological, psychiatric, endocrine, cardiovascular, respiratory, gastrointestinal, hepatic, or renal disorder that may aggravate due to study participation and jeopardize the health status of the patient. 7. Any infection within 1 month prior to the anticipated dosing day. 8. Any indication of past or present tuberculosis. 9. Positive Hepatitis B surface antigen (HBsAg), Hepatitis C antibody (HCV Ab), or human immunodeficiency virus antibody (HIV Ab) at screening. 10. History of alcohol or substance abuse 11. Use of CYP3A4-inhibiting drugs or food (grapefruit, grapefruit juice, grapefruit-containing products, Seville oranges, or pomelo-containing products, and quinine containing drinks within 14 days prior to day –1. 12. Participation in an investigational drug or device study within 3 months prior to screening. 13. Donation of blood over 500 mL within three months prior to screening. 14. Vaccination within 6 weeks prior to start of treatment or planned vaccination up to 90 days after the final dose. 15. Unwillingness or inability to comply with the study protocol for any other reason.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine the safety, tolerability, pharmacokinetics and pharmacodynamic effects of liposomal dexamethasone (Oncocort™) in patients with metastatic prostate cancer. ;Secondary Objective: To determine pharmacodynamic effects of liposomal dexamethasone (Oncocort) in patients with metastatic prostate cancer.; Primary end point(s): Standard safety and tolerability measurements are listed below, and will be assessed according to the visit- and assessment schedule (Table 2). - Concomitant medication - Clinical laboratory tests (Haematology / Chemistry / Urinalysis) - Complement activation - Vital signs (Pulse Rate, Blood pressure, Temperature) - Electrocardiogram (HR, PR, QRS, QT) If indicated additional diagnostics will be performed and treatment-emergent (serious) adverse events ((S)AEs) will be registered. ; Timepoint(s) of evaluation of this end point: Evaluation of safety and tolerability will be assessed at least 4 days after dosing the first subject, before continuation to the next dose and start of the remaining subjects. Additional safety and tolerability parameters will be evaluated throughout the study and will be reported afterwards. | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: Pharmacokinetec endpoints will be evaluated after phase 1, and again at end of study All other secondary end points will be evaluated at the end of study. ; Secondary end point(s): Pharmacokinetic endpoints The following endpoints will be determined and will be measured as according to the visit- and assessment schedule for liposomal and free dexamathosone following each treatment. They will be derived by non-compartmental analysis of the plasma concentration-time data: - The maximum concentration (Cmax) - The time to reach maximum plasma concentration (tmax); - The area under the concentration-time curve from zero to t of the last measured concentration above the limit of quantification (AUC0-last) - The terminal disposition rate constant (?z) with the respective half-life (t½). - The area under the concentration-time curve from zero to infinity(AUC0-inf). Other parameters, including Vz, CL, and other parameters as appropriate, as well as dose adjusted parameters, may be determined. Pharmacodynamic effect endpoints Absolute values and change from baseline to each time point of measurement will be summarized using individual values or summated response measures (e.g. AUC). - PSA; - Alkaline phosphatase - Cortisole - Sex steroids (testosterone, estradiol, FSH, LH and SHBG); - Fasting blood glucose; - Lymphocyte count; - Activation of complement - Comprehensiveness of bone metastases, as assessed in Scintigraphy/CT/MRI; | — |
Countries
Netherlands
Contacts
Public ContactCRO
Centre for human drug research
Outcome results
None listed