Metastatic Prostate Cancer
Conditions
Interventions
Oncocort*
Liposomal dexamethasone
Prostate cancer
Sponsors
Enceladus Pharmaceuticals B.V.
Eligibility
Age
18 Years to 64 Years
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; 4. Not yet, or no longer being eligable for other, registered therapy other than corticosteroids. 5. Live expectancy in good clinical condition (WHO 0-1) and live expectancy of more than 3 months.
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. Positive Hepatitis B surface antigen (HBsAg), Hepatitis C antibody (HCV Ab), or human immunodeficiency virus antibody (HIV Ab) at screening. 9. History of alcohol or substance abuse 10. Use of CYP3A4-inhibiting drugs or food (grapefruit, grapefruit juice, grapefruit-containing products, Seville oranges, or pomelo-containing products, and quinine containing drinks within 11 days prior to day of dosing. 11. Participation in an investigational drug or device study within 3 months prior to screening. 12. Donation of blood over 500 mL within three months prior to screening. 13. Vaccination within 6 weeks prior to start of treatment or planned vaccination up to 90 days after the final dose. 14. Unwillingness or inability to comply with the study protocol for any other reason. 15. Expected fulminant progression of disease
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Safety and tolerability Assessed using adverse event reporting, standard clinical measures (vital signs, ECG), routine laboratory assessments and activation of complement during infusion. Pharmacokinetic endpoints Extensive PK sampling will be performed in each of the 10 patients after the first dose of 10 mg and after the first dose of 20 mg. Optionally, additional PK sampling will be performed, guided by PK data obtained in part I. A validated bioanalytical assay will be used to determine the concentrations of liposomal and free dexamethasone in plasma after Oncocort administration. The following pharmacokinetic variables will be calculated, if possible: - Area under the plasma concentration-time curve (AUC) from time 0 to the time of the last quantifiable concentration (AUC0-t) and from time 0 extrapolated to infinity (AUC0-inf); - Maximal observed plasma drug concentration (Cmax); - Time to maximum observed plasma drug concentration (tmax); - Half-life (t *); - Volume of distribution (Vd); - Clearance. Pharmacodynamic effect endpoints - PSA; - Bone marker: alkaline phosphatase; - Cortisole; - Sex steroids (testosterone, estradiol, FSH, LH and SHBG); - Fasting blood glucose; - Lymphocyte count; - Activation of complement; AP and CP - Comprehensiveness of bone metastases, as assessed in Scintigraphy/CT/MRI; | — |
Countries
The Netherlands
Outcome results
None listed