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

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)).

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))

Study Overview

• Status: Completed
• Conditions: Prostate Cancer
• Intervention / Treatment: Drug: 2-Hydroxyflutamide Depot

Detailed Description

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
• Enrollment (Actual): 61
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3H 2Y9
      • Nova Scotia Health Authority
  • Ontario
    • Brampton, Ontario, Canada, L6T 4S5
      • Jonathan Giddens Medicine Professional Corporation
    • Burlington, Ontario, Canada, L7N 3V2
      • G. Kenneth Jansz Medicine Professional Corporation
    • Oakville, Ontario, Canada, L6H 3 P1
      • The Fe/Male Health Centres
    • Toronto, Ontario, Canada, M4N 3M5
      • Sunnybrook Health Sciences Centre
  • Quebec
    • Sherbrooke, Quebec, Canada, J1H 5N4
      • CIUSSS de l'Estrie - CHUS
• Finland
  • Helsinki, Finland, FIN-00100
    • Helsinki University Hospital
  • Tampere, Finland, Fi-33521
    • Tampere University Hospital
• Lithuania
  • Kaunas, Lithuania, 50161
    • Hospital of Lithuanian University of Health Sciences
  • Vilnius, Lithuania, 08660
    • National Cancer Institute - Oncourology Department

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Stage I: Dose = 35% of prostate volume; Subject will be randomized into a group receiving one dose of 2-hydroxyflutamide depot (Liproca® Depot) equal to 35 % of their prostate volume.	Drug: 2-Hydroxyflutamide Depot; Liproca® Depot is a depot formulation containing a bioresorbable, controlled-release,formulation of the nonsteroidal antiandrogen 2-hydroxyflutamide; Other Names: Liproca® Depot Injection
Experimental: Stage I: Dose = 45% of prostate volume; Subject will be randomized into a group receiving one dose of 2-hydroxyflutamide depot (Liproca® Depot) equal to 45 % of their prostate volume.	Drug: 2-Hydroxyflutamide Depot; Liproca® Depot is a depot formulation containing a bioresorbable, controlled-release,formulation of the nonsteroidal antiandrogen 2-hydroxyflutamide; Other Names: Liproca® Depot Injection
Experimental: Stage II: Dose = 16mL; Subject will be randomized into a group receiving one dose of 2-hydroxyflutamide depot (Liproca® Depot) equal to 16mL	Drug: 2-Hydroxyflutamide Depot; Liproca® Depot is a depot formulation containing a bioresorbable, controlled-release,formulation of the nonsteroidal antiandrogen 2-hydroxyflutamide; Other Names: Liproca® Depot Injection
Experimental: Stage II: Dose = 20mL; Subject will be randomized into a group receiving one dose of 2-hydroxyflutamide depot (Liproca® Depot) equal to 20mL	Drug: 2-Hydroxyflutamide Depot; Liproca® Depot is a depot formulation containing a bioresorbable, controlled-release,formulation of the nonsteroidal antiandrogen 2-hydroxyflutamide; Other Names: Liproca® Depot Injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Highest Tolerable Dose of Liproca Depot	To define the highest tolerable dose of Liproca Depot for transrectal injection into the prostate.	24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	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.	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.	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.	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.	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.	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.	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.	24 weeks

Collaborators and Investigators

• Sponsor: Lidds AB
• Collaborators: CMX Research

Study record dates

Study Major Dates

• Study Start (Actual): May 12, 2017
• Primary Completion (Actual): October 30, 2020
• Study Completion (Actual): November 30, 2020

Study Registration Dates

• First Submitted: November 1, 2017
• First Submitted That Met QC Criteria: November 17, 2017
• First Posted (Actual): November 21, 2017

Study Record Updates

• Last Update Posted (Actual): December 21, 2020
• Last Update Submitted That Met QC Criteria: December 18, 2020
• Last Verified: December 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Prostatic Neoplasms; Physiological Effects of Drugs; Hormones, Hormone Substitutes, and Hormone Antagonists; Hormone Antagonists; Androgen Antagonists; Hydroxyflutamide
• Other Study ID Numbers: LPC-004

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No