A Phase I-IIa, Open label, Multi-Center, Dose Escalating Study to Evaluate the Safety, Pharmacokinetics and Pharmacodynamics of Intravenous Pegylated Liposomal Dexamethasone Sodium Phosphate as Monotherapy in Patients with Metastatic Prostate Cancer

Short Title:
Intravenous liposomal dexamethasone in patients with metastatic prostate cancer

A NanoNextNL programme (Technology Foundation STW ⁄ Nanotechnology Cluster ⁄ Programme Office NanoNextNL) valorisation grant has been obtained by Encelades, Department of Oncology and Urology of the Leiden University Medical Center (Osanto and Pluijm) and EUOG to study the clinical effects of liposomal dexamethasone in metastatic prostate cancer patients. The study is being carried out in the CHDR phase I unit and is currently ongoing.

Background & Rationale

For over 30 years corticosteroids have been used in the management of castration resistant prostate cancer (CRPC). Single agent prednisone 7.5–10 mg daily was initially used in the management of metastatic CRPC patients (mCRPC) and subsequent studies showed clinical benefit in these patients. In phase 3 trials the response rate of prostate-specific antigen (PSA) to prednisolone ranged from 9% to 33%, and the median time to PSA progression has ranged from 2 to 6.6 months.
Until recently, dexamethasone has been less well studied in the treatment of CRPC. Phase 2 studies of low-dose, daily dexamethasone have reported higher PSA response rates of 50–60%, with median time to PSA progression of 7-8 months. Two large studies reported PSA response rates of around 50%.
More recent data suggest that dexamethasone is more effective with a similar side-effect profile and may be the most efficacious corticosteroid for use as monotherapy in CRPC patients. The higher antitumor activity for dexamethasone supports its use in the clinic in mCRPC patients.
A preclinical animal study underscore the use of liposomal dexamethasone in prostate cancer metastatic to the bone.
The use of long-circulating liposomal delivery of glucocorticosteroids may have therapeutic efficacy while circumventing adverse systemic effects of the use of glucocorticosteroids.

Aim of the study

To determine the tolerability, pharmacokinetics and pharmacodynamics of liposomal dexamethasone (ONCOCORT™) in patients with metastatic prostate cancer.

Study design

The current trial is a first study with Oncocort™ monotherapy in patients with metastatic prostate cancer with the objective to assess safety, tolerability, efficacy and dose response after short-term treatment with repeated infusions.

Investigational drug

The investigational drug Oncocort™ (Encelades) consists of dexamethasone disodium phosphate encapsulated in so-called ‘long-circulating’ PEGylated liposomes which is in development to provide enhanced and prolonged lesion uptake of dexamethasone in patients with prostate cancer.