Castration-resistant metastatic prostate cancer Cancer Malignant neoplasm of prostate
Conditions
Interventions
Intravenous pegylated liposomal dexamethasone sodium phosphate
Part A (patients 1-5): doses of 10 and 20 mg, dosing of 10 mg on day 1, dosing of 20 mg on days 8, 22, 36, 50 and day 64
Sponsors
Enceladus Pharmaceuticals (Netherlands)
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 4. Not yet, or no longer eligible for other, registered therapy other than glucocorticoids 5. Live expectancy in good clinical condition (WHO 0-1) for 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 patient 2. Contraindication for glucocorticoids as judged by clinician or 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 drug administration 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 14 days prior to dosage 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 1. Blood chemistry and haematology and Vital signs: 1.1. Heart rate (bpm), 1.2. Systolic and diastolic blood pressure (mmHg), 1.3. Breath frequency (breaths per minute), and 1.4. Temperature (degrees Celsius) are assessed for clinically significant abnormalities. Measurements are taken at screening (up to -28 days before the first dose) and at follow-up (10 weeks after study start). For participants in part A it is measured on days 1, 2, 5, 8, 9, 12, 22, 36, 50, 64, and participants in part B on days 1, 2, 4, 8, 9, 12, 15, 22, 29, 36, 43, 50, 57, 64. 1.5. ECGs are made and assessed for clinically significant abnormalities at screening and follow-up and for participants in part A on days 1, 2, 5, 8, 9, 12, 22, 36, 50, 64, and participants in part B on days 1, 2, 4, 8, 9, 12, 15, 22, 29, 36, 43, 50, 57, 64. 2. Routine laboratory assessments are measured, by assessment of blood chemistry (Sodium, chloride, potassium, calcium, inorganic phosphate, total protein, albumin, total cholesterol, triglycerides, glucose, creatinine, uric acid, total bilirubin2, alkaline phosphatase, AST, ALT, gamma-GT and LDH) and haematology: 2.1. Haemoglobin 2.2. Mean Corpuscular volume (MCV) 2.3. Mean corpuscular haemoglobin (MCH) 2.4. Mean corpuscular haemoglobin concentration (MCHC) 2.5. Haematocrit 2.6. Red cell count (RBC) 2.7. Total white cell count (WBC) 2.8. Leukocyte differential count 2.9. Platelet count 2.10. Differential blood count, including: basophils, eosinophils, neutrophils, lymphocytes, and monocytes. These laboratory outcomes are measured for participants in part A on days 1, 2, 5, 8, 9, 12, 22, 36, 50, 64, and participants in part B on days 1, 2, 4, 8, 9, 12, 15, 22 | — |
Secondary
| Measure | Time frame |
|---|---|
| Pharmacokinetics and pharmacodynamics of liposomal dexamethasone (Oncocort™) in patients with metastatic prostate cancer from baseline to end of study. 1. Pharmacokinetic endpoints: PK is measured by blood sampling at baseline, 1h, 2h, 3h, 4h, 6h, 8h, 12h, 24h, 48h and 96 hours after dosing on days 1 and 8. In addition, patients in Part B have a pre-dose sample on days 12, 15, 22, 29, 36, 43, 50, 57, 64. From these samples, the serum concentrations of dexamethasone and dexamethasone phosphate were measured 2. Pharmacodynamic effect endpoints: Pharmacodynamic effects are measured by: 2.1. Comprehensiveness of bone metastases as assessed in scintigraphy/CT at 10 weeks compared to baseline 2.2. Complement activation at baseline, after 24 hours and pre-dose on day 8 2.3. PSA, cortisol, sex steroids, fasted glucose, lymphocyte count, at screening and follow-up and on days 1, 22, 36, 50 | — |
Countries
Netherlands
Contacts
Public ContactJosine Vrouwe
Outcome results
None listed