An Efficacy and Safety Study With Licroca Depot, a Controlled Release Product, Injected Into the Prostate (2-HOF)

An Open, Single and Multiple Dose, Efficacy and Safety Proof of Principle Study of Liproca Depot, a Controlled Release Formulation of 2-hydroxyflutamide, Injected Into the Prostate in Patients With Localized Prostate Cancer

The primary objective was to evaluate efficacy of a single dose of Liproca Depot in patients with localized prostate cancer. Primary efficacy variable was the proportion of patients showing PSA nadir. 24 Caucasian men, with a mean age at inclusion of 68.4 years, with localized prostate cancer were injected once with a ready made paste including 600 mg 2-hydroxyflutamide (Liproca Depot) into the site of the prostate where the tumour was localized. The patient was monitored for prostate-specific antigen (PSA) for maximum 6 months or to progression within this time period. The primary endpoint showed interesting results with high success rate (83%), i.e. proportion of patients (Responders) that reached plasma PSA nadir.

Study Overview

• Status: Completed
• Conditions: Prostate Cancer
• Intervention / Treatment: Drug: 2-hydroxyflutamide (2-HOF) [Liproca Depot]; Drug: 2-Hydroxyflutamide

Detailed Description

Patients with localized prostate cancer were followed to progression or maximum 24 weeks after a single injection in one lobe of 2-8 mL ready-made paste (corresponding to 400-1600 mg 2-Hydroxyflutamid). Progression was defined as an increase in PSA by > 25% over baseline or on-treatment nadir.Among the 24 patients the primary endpoint, plasma PSA nadir, was reached by 20 patients (Responders). Efficacy was measured primarily as PSA nadir, and secondly as time to PSA nadir and prostate volume change. Safety was monitored throughout the whole study period.

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Finland
  • Tampere, Finland
    • Tampere University Hospital
  • Tampere, Finland, 33520
    • Tampere University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 45 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

1. Age ≥ 45years
2. Histologically confirmed localized prostate cancer (T1-T2), predominantly in one side of the peripheral zone, verified by biopsy.
3. PSA value < 20 ng/ml within 6 weeks before enrolment.
4. Gleason score ≤ 3+4 at diagnostic biopsy
5. Adequate renal function: Creatinine < 1.5 times upper limit of normal.
6. Adequate hepatic function: ASAT, ALAT and ALP < 1.5 times upper limit of normal.
7. Negative dipstick for bacturia.
8. Patient must have ability to cope with the study procedures and to return to scheduled visits including follow up visit.

Exclusion Criteria:

1. Previous or ongoing hormone therapy for prostate cancer.
2. Ongoing or previous therapy (within3 month) of finasteride or dutasteride.
3. Ongoing or previous invasive therapy for benign prostate hyperplasia (TURP, TUMT).
4. Symptoms or signs of acute prostatitis.
5. Symptoms or signs of ulceric proctitis
6. Severe micturation symptoms (I-PSS >17)
7. Concomitant systemic treatment with corticosteroids, or immunomodulating agents.
8. Known immunosuppressive disease (e.g. HIV, insulin dependent diabetes).
9. Simultaneous participation in any other study involving not market authorized drugs or having participated in a study within the last 12 months prior to start of study treatment.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: 2-Hydroxyflutamide; Single injection of 2-Hydroxyflutamide (2-8mL ready-made paste)in one prostate lobe

Drug: 2-hydroxyflutamide (2-HOF) [Liproca Depot]; Ready made paste including 600 mg 2-HOF for injection as a single dose; Other Names: Liproca Depot; Drug: 2-Hydroxyflutamide; The Product consists of two sterile components, one aqueous liquid and a dry powder, containing the active drug 2-Hydroxyflutamide (2-HOF. The two components were mixed under aceptic conditions to a paste prior to administration.; Other Names: Liproca Depot

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of Patients Showing PSA Nadir	Plasma PSA nadir is the lowest PSA reading achieved after any treatment for prostate cancer. The patients were observed once every 4th week during the study period.	Measured every 4th week until progression or maximum 6 months.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Patients Reporting Adverse Events Caused by the Study Treatment	Adverse events caused by the study treatment; Abnormal, clinically relevant, laboratory parameters; Voiding symptoms; Vital Signs; Quality of Life	Measured every 4th week till progression or maximum 6 months
Percent Change in Prostate Volume From Baseline to Nadir.	Prostate volume was measured at each visit to capture nadir and compared to baseline for all patients. Decrease in prostate volume is reported as percent change from baseline.	Measured every 4th week until progression or maximum 6 months.
Time to PSA Nadir	Time frame was from baseline to day of PSA nadir.	Measured every 4th week until progression or maximum 6 moths.
Percent Change in Prostate Volume From Baseline to Final Visit	Prostate volume was captured at each visit and percent change from baseline to final visit was measured. Final visit was either day of progression or after 6 months. Prostate volume decrease is reported in percent change from baseline	Measured every 4th week until progresion or maximum 6 months.
Number of Days to Prostate Volume Nadir.	Number of Days from day of injection to prostate volume nadir.	Measured every 4th week until progression or maximum 6 months.

Collaborators and Investigators

• Sponsor: Lidds AB
• Investigators: Principal Investigator: Teuvo Tammela, Professor, Tampere University Hospital

Study record dates

Study Major Dates

• Study Start: June 1, 2009
• Primary Completion (Actual): May 1, 2011
• Study Completion (Actual): July 1, 2011

Study Registration Dates

• First Submitted: June 3, 2009
• First Submitted That Met QC Criteria: June 3, 2009
• First Posted (Estimate): June 4, 2009

Study Record Updates

• Last Update Posted (Estimate): January 19, 2015
• Last Update Submitted That Met QC Criteria: January 15, 2015
• Last Verified: April 1, 2013

More Information

Terms related to this study

• Keywords: Prostate cancer
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Prostatic Neoplasms; Physiological Effects of Drugs; Antineoplastic Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Hormone Antagonists; Androgen Antagonists; Flutamide; Hydroxyflutamide
• Other Study ID Numbers: LPC-002; 2009-010079-25 (EudraCT Number)