A Study to Evaluate the Safety, Tolerability and Efficacy of a Liproca® Depot Injection in Patients With Prostate Cancer

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.

Inclusion criteria

• Signed informed consent prior to any study specific procedures being performed
• 18 - 80 years of age, inclusive
• Assigned to Active Surveillance
• Histologically confirmed, localized prostate cancer within 24 months of Screening
• Gleason score 3+3 or 3+4 with one or more of the following characteristics:

PSA > 6.0 μg/L (ng/mL) and PSA density > 0.15; PSA > 10.0 μg/L and < 20 μg/L (ng/mL); Any systematic core > 50% involvement; Any PI-RADS score 4 or 5 on MRI; Any Gleason grade 4, Men of African descent

• Patient has a negative bone scan within the last 12 months
• Patient is able to have an MRI
• Prostate volume ≤ 80 mL (measured by MRI within 12 months of Screening or has been scheduled for an MRI prior to Screening)
• eGFR ≥ 30 mL/min, using the Cockcroft - Gault Equation: = [{(140 - age in years) x (weight in kg)} x 1.23] / serum Creatinine in micromol/l
• AST, ALT and ALP ≤ 1.5 times upper limit of normal
• Patient must be willing to comply with all study procedures
• Patients must agree to the use of medically acceptable methods of contraception, including non-hormonal intrauterine device (IUD) or double barrier method (condom with foam or vaginal spermicidal suppository, diaphragm with spermicide) for the duration of the study (24 weeks), unless the patient and/or their partner has been surgically sterilized

Exclusion criteria

• PSA > 20 μg/L (ng/mL)
• Previous or ongoing hormonal therapy for prostate cancer
• Positive urine culture before treatment with prophylactic antibiotics
• Ongoing or previous therapy with finasteride or dutasteride in the last 3 months
• Ongoing or previous invasive therapy for benign prostate hyperplasia (BPH) (e.g. TURP,TUMT, HIFU, etc.)
• Use of pacemaker or other implanted electronic devices
• Metal implant in the pelvis (e.g. hip replacement) that may affect the MRI of the prostate
• Allergy to Liproca® Depot and its ingredients
• Severe micturition symptoms (I-PSS >15 or residual urine volume > 150 mL) confirmed by repeat measurement or Qmax< 12 mL/s
• Ongoing therapy with the anticoagulant Acetyl Salicylic Acid (ASA) (more than 100mg/day) as preventive anti-thrombotic therapy should be withdrawn temporarily before treatment with Liproca® Depot, as determined by the Investigator. Other anticoagulants should be withdrawn in cooperation with the treating physician
• Use of any previous focal prostate cancer treatment, such as transurethral resection, cryotherapy, high intensity frequency ultrasound (HIFU) and/or photodynamic therapy
• Concomitant systemic treatment with corticosteroids or immune modulating agents
• Known immunosuppressive disease (e.g. HIV, Type II Diabetes). Patients with well controlled Type II Diabetes may be included, as determined by Investigator
• Simultaneous participation in any other study involving an investigational product or device,or having participated in a prostate cancer study within the last 12 months prior to starting treatment with Liproca® Depot
• Infection in WHO Risk Group 2, 3 or 4