A Single Blind, Two-Stage Dose Finding Study to Evaluate the Safety, Tolerability and Efficacy of a Single Liproca® Depot Injection into the Prostate in Patients with Localized Prostate Cancer,Assigned to Active Surveillance who are at High Risk for Disease Progression (followed by an Open Label Extension with a Repeat Injection (Optional))
Patients assigned to Active Surveillance and who have fulfilled all inclusion criteria will receive a prophylactic antibiotic and a local anaesthetic (according to the Investigator's Standard of Care) prior to administration of Liproca® Depot. 60 subjects will be enrolled. The Single Dose Study will be conducted in two stages: In Stage I, 20 subjects will be randomized into two groups to receive one dose of Liproca® Depot equal to 35% (Cohort 1) or 45 % (Cohort 2) of their prostate volume (mL) (N=10:10). Two weeks after all subjects have received their initial dose, the Data Safety Monitoring Board (DSMB) will review the subjects' safety and tolerability data over the first 14 days after receiving treatment. In Stage II, 40 subjects will be randomized to receive either 16mL (Cohort 3) or 20mL (Cohort 4) of Liproca® Depot. All subjects in Stage I and Stage II will be followed for 24 weeks. Subjects who complete the Single Dose Study and who experience no safety or tolerability issues, as determined by the Investigator, may be offered an option to participate in the Open Label Extension Study (OLE). Subjects enrolled in the OLE will be observed for PSA recurrence every 8 weeks. If PSA recurrence is confirmed (defined as a PSA level exceeding at least 100 % of Baseline value) subjects will receive a second treatment of Liproca® Depot. The dose will be injected into the tumour focus/foci and in close proximity to the tumour, based on a prostate biopsy (and MRI, if applicable), using a TRUS for guidance. Stage I subjects who received 35% volume of Liproca® Depot will receive 16 mL and subjects who received 45% volume of Liproca® Depot will receive 20 mL. Stage II subjects will receive the same dose of Liproca® Depot that was administered in the first treatment. Subjects in the OLE receiving a second injection will be followed up for an additional 24 weeks for safety, tolerability and efficacy. After this period, subjects may undergo MRI imaging and a prostate biopsy.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
SINGLE
Enrollment
61
Liproca® Depot is a depot formulation containing a bioresorbable, controlled-release,formulation of the nonsteroidal antiandrogen 2-hydroxyflutamide
Nova Scotia Health Authority
Halifax, Nova Scotia, Canada
Jonathan Giddens Medicine Professional Corporation
Brampton, Ontario, Canada
G. Kenneth Jansz Medicine Professional Corporation
Burlington, Ontario, Canada
Highest Tolerable Dose of Liproca Depot
To define the highest tolerable dose of Liproca Depot for transrectal injection into the prostate.
Time frame: 24 weeks
Liproca Depot Effect on Prostate Specific Antigen Levels
To determine the absolute level and % decrease of PSA level at Week 8, 16, 20 and 24, and PSA nadir.
Time frame: 24 weeks
Liproca Depot Effect on Prostate Volume
To determine the effect on prostate volume at Week 20 after treatment with one of four doses of Liproca Depot based on an MRI evaluation. Measured by %decrease versus Baseline and as absolute values.
Time frame: 20 weeks
Evaluation of Lesions
MRI evaluation of Lesions based on PI-RADS (Prostate Imaging Reporting and Data System) score 20 weeks after treatment with one of four doses of Liproca Depot.
Time frame: 20 weeks
Quality of Life (QoL) Questionnaire Score
Assessment of QoL Questionnaire scores at Baseline, Week 8,16,20 and 24 after treatment with one of four doses of Liproca Depot.
Time frame: 24 weeks
Micturition Status using the International Prostate Symptom Score (I-PSS)
Micturition status will be assessed using the I-PSS Questionnaire at Week 8, 20 and 24 after treatment with one of four doses of Liproca Depot.
Time frame: 24 weeks
Frequency of Adverse Events
All adverse events related to Liproca Depot or its administration, incidence of AEs, withdrawals due to AEs and all Serious Adverse Events (SAEs) will be assessed. All adverse events will be reported and followed until resolved or until, in the Investigator's opinion, the condition has become stable and is unlikely to change further.
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The Fe/Male Health Centres
Oakville, Ontario, Canada
Sunnybrook Health Sciences Centre
Toronto, Ontario, Canada
CIUSSS de l'Estrie - CHUS
Sherbrooke, Quebec, Canada
Helsinki University Hospital
Helsinki, Finland
Tampere University Hospital
Tampere, Finland
Hospital of Lithuanian University of Health Sciences
Kaunas, Lithuania
National Cancer Institute - Oncourology Department
Vilnius, Lithuania
Time frame: 24 weeks
Change in Testosterone Levels
Testosterone levels (nmol/L) will be assessed at Baseline, Week 8 and 24 after treatment with one of four doses of Liproca Depot.
Time frame: 24 weeks
Systematic Exposure of 2-hydroxyflutamide
To examine the systematic exposure of 2-hydroxyflutamide at Baseline, Hour 2, Day 2,4,7 and 14, week 8 and end of study for all subjects in Phase I and a subset of 12 subjects in Stage II.
Time frame: 24 weeks
Pharmacokinetics of 2-hydroxyflutamide
To examine the pharmacokinetics of 2-hydroxyflutamide at Baseline, Hour 2, Day 2,4,7 and 14, week 8 and end of study for all subjects in Phase I and a subset of 12 subjects in Stage II.
Time frame: 24 weeks