Efficacy and Safety Study of TOOKAD® Soluble for Localised Prostate Cancer Compared to Active Surveillance.

Study Overview
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Brief Summary
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The aims of this study are: to assess the impact of TOOKAD® Soluble-Vascular Targeted Photodynamic Therapy (VTP) on the rate of absence of definite cancer using patients on active surveillance as a comparison (co-primary objective A) and to determine the difference in rate of treatment failure associated with observed progression of disease from low risk prostate cancer to moderate or higher risk prostate cancer in men who undergo TOOKAD® Soluble-VTP compared to men on active surveillance (co-primary objective B).

Detailed Description
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This is a Phase 3, multicentre, open label, randomised controlled study in subjects diagnosed with low risk prostate cancer on TransRectal Ultrasound (TRUS) guided biopsy. Subjects will be randomised to either Active Surveillance or TOOKAD® Soluble VTP. Subjects will remain in the study for approximately 24 months following randomisation. A total of 400 subjects will be entered into the study; 200 will receive Active Surveillance and 200 will receive TOOKAD® Soluble-VTP.

Official Title
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A European Randomised Phase 3 Study to Assess the Efficacy and Safety of TOOKAD® Soluble for Localised Prostate Cancer Compared to Active Surveillance

Conditions
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Prostate Cancer

Intervention / Treatment
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* Drug: TOOKAD® Soluble


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects will be eligible for inclusion in the study if all of the following criteria are met: Low risk prostate cancer diagnosed using one transrectal ultrasound guided biopsy (TRUS)using from 10 to 24 cores performed less than 12 months prior to enrolment, and showing the following: Gleason 3 + 3 prostate adenocarcinoma as a maximum, Two (2) to three (3) cores positive for cancer A maximum cancer core length of 5 mm in any core. Cancer clinical stage up to T2a (pathological or radiological up to T2c disease permitted) Serum prostate specific antigen (PSA) of 10 ng/mL or less Prostate volume equal or greater than 25 cc and less than 70 cc. Male subjects aged 18 years or older. Exclusion Criteria: Subjects will not be eligible for the study if meeting any of the following criteria: Unwillingness to accept randomisation to either of the two arms of the study Any prior or current treatment for prostate cancer, including surgery, radiation therapy (external or brachytherapy) or chemotherapy. Any surgical intervention for benign prostatic hypertrophy Life expectancy less than 10 years. Any condition or history of illness or surgery that may pose an additional risk to men undergoing the VTP procedure. Participation in another clinical study or recipient of an investigational product within 1 month of study entry. Subject unable to understand the patient's information document, to give consent or complete the study tasks. Subject in custody and or in residence in a nursing home or rehabilitation facility Contra-indication to Magnetic resonance Imaging (MRI) (e.g., pacemaker, history of allergic reaction to gadolinium), or factors excluding accurate reading of pelvic MRI (e.g., hip prosthesis) Any condition or history of illness or surgery that may pose an additional risk to men undergoing the TOOKAD® Soluble VTP procedure.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TOOKAD® Soluble<br>TOOKAD® Soluble, lyophilized formulation, given at a dose of 4mg/Kg. | Drug: TOOKAD® Soluble<br>* TOOKAD® Soluble-VTP procedure will consist of an IntraVenous (IV) administration to patients using a 753nm laser light at a fixed power of 150mW/cm and a fixed energy at 200J/cm delivered through transperineal interstitial optical fibers. The needles are positioned in the prostate under ultra sound image guidance<br>* Other names: WST11;|
| No Intervention: Active Surveillance<br>Active surveillance is one of the management strategy in men who have low-risk prostate cancer | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Co-primary endpoint 'A': Rate of absence of definite cancer using patients on active surveillance as a comparison. | Histological changes are assessed using biopsies or any other pathology result obtained during the study planned or not. | Month 24 | 
| Co-primary endpoint 'B': Difference in rate of treatment failure associated with observed progression of disease from low risk prostate cancer to moderate or higher risk prostate cancer. | Moderate or higher risk is defined as the observation of: More than 3 cores positive for cancer when considering all histological examination available during follow-up of study; or any Gleason primary or secondary pattern 4 or more; or at least one cancer core length greater than 5 mm; or PSA>10ng/mL ( in 3 consecutive measures); or any T3 prostate cancer, or metastasis; or prostate cancer related death | Over 24 months follow-up. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The rate of additional prostate cancer radical therapy | Number of patients undergoing a radical treatment for prostate cancer such as: radical prostatectomy, radiotherapy, brachytherapy divided by the total number of patients. | Over 24 months follow-up | 
| Total number of cores positive for cancer | Total number of biopsy sample containing tumor cells at the month 24 biopsy | Month 24 | 
| The rate of incontinence, erectile dysfunction, urinary symptoms | Number of patients experiencing urinary incontinence, erectile dysfunction or urinary symptoms events divided by the total number of patients. | Randomisation visit, Day 7 after VTP , Month 3, Month 6, Month 9, Month 12, Month 24 | 
| The rate of adverse events | Number of patients experiencing adverse events divided by the total number of patients. | Screening-Month 24 | 
| The rate of severe prostate cancer related events: cancer extension to T3, metastasis and prostate cancer related death | Number of patients experiencing severe prostate cancer related events: cancer extension to T3, metastasis and prostate cancer related death divided by the total number of patients. | Screening-Month 24 | 
| The overall quality of life will be recorded for potential utility and descriptive studies. | Results of the International Index of Erectile Function (IIEF) and International Prostate Symptoms Score (IPSS) patients questionaires. | Randomisation visit; Month 12; Month 24 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Prostatic Disease, Genital Neoplasm,male, Urogenital neoplasm, Genital disease,male, Male urogenital disease, Neoplasms, Neoplasms by site, Prostatic neoplasm, Carcinoma