Safety and Tolerability Study Using WST11 In Patients With Localized Prostate Cancer

Study Overview
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Brief Summary
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The aim of this study is to determine the optimal treatment conditions (WST11 dose and light energy dose) to achieve ablation in one lobe of the prostate and to evaluate the safety and quality of life of WST11 medicated Vascular-Targeted Photodynamic therapy (VTP) in men with localized prostate cancer.

Detailed Description
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This study is designed as a multicenter, phase I/II, prospective, open-labeled, single intravenous (IV) dose, clinical trial in patients with localized prostate cancer. The study population will be men who have been offered curative therapy (radical prostatectomy; cryotherapy; brachytherapy; External Beam RadioTherapy (EBRT), and refused. Patients must have already had a previous biopsy showing a histologically proven carcinoma of the prostate. The identification and the location of the tumor will be done using both dynamic contrast Magnetic resonance Imaging (MRI) and biopsy. Only unilateral treatment with WST11-medicated VTP will be performed during the study. Treatment will consist of a single, 10 minute, IV administration of WST11 at doses of 2mg/kg, 4 mg/kg or 6 mg/kg, followed by either light activation delivered through transperineal interstitial optical fibers for 20 minutes using 753 nm laser light at escalating fixed energy doses of 200 J/cm or 300 J/cm by escalating power at each energy to 167 mW/cm or 250 mW/cm respectively. A brachytherapy-like template is used for the placement of the transparent implant catheters which are positioned in the prostate under transrectal ultrasound image guidance. The illumination fiber(s) are then inserted into the implant catheters. If the safety profile for a given WST11 and light dose is acceptable, additional patients may be treated with multiple fibers at that WST11 treatment dose. For cases where the Month 6 biopsy is positive, the patient will be offered the opportunity to be retreated with WST11

Official Title
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A Prospective, Multicenter Phase I/II Safety and Tolerability Study of Unilateral Vascular-Targeted Photodynamic Therapy Using WST11 in Patients With Localized Prostate Cancer

Conditions
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Prostate Cancer

Intervention / Treatment
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* Drug: WST 11 -mediated -VTP


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: At least 18 years of age Diagnosed with localized, prostate cancer and who have been offered curative therapy (radical prostatectomy; cryotherapy; brachytherapy; External Beam RadioTherapy (EBRT), and refused Localized prostate cancer stage T1C up to T2A based on biopsy performed at least 6 weeks prior to enrollment Gleason score ≤ 3+3 with ≤50% of sampled cores positive, and each positive core having a tumour length of ≤5 mm Prostate Specific Antigen (PSA) < 10 ng/mL No prior treatment for prostate cancer Signed Informed Consent Form Exclusion Criteria: Any condition or history of illness or surgery that, in the opinion of the investigator and/or the Sponsor, might confound the results of the study or pose additional risks to the patient. All patients whose current pre-operative cardiac evaluation does not show their fitness for a procedure requiring general anesthesia; Patients with a prior history of viral or alcoholic hepatitis, and other patients felt to be at risk for hepatotoxicity including concomitant use of potentially hepatotoxic medications or dietary supplements; Patients with a history of inflammatory bowel disease or other factors which may increase the risk of fistula formation; Patients who have received any hormonal manipulation (excluding 5-alpha reductase inhibitors) or androgen supplements within the previous 6 months; Patients previously treated by radiation therapy (external therapy or brachytherapy) or chemotherapy or any therapy for prostate cancer; Patients who have received or are receiving chemotherapy for prostate carcinoma or other significant cancer; Patients who have undergone previous TURP (trans-urethral resection of the prostate); Patients with a history of urethral stricture disease Patients with a history of acute urinary retention Patients who are currently (within 10 days before the treatment procedure) receiving any medications having potential photosensitizing effects (e.g. tetracyclines, sulfonamides, phenothiazines, sulfonylurea hypoglycemic agents, thiazide diuretics and griseofulvin) Patients who are currently receiving anticoagulant drugs (within 10 days before the treatment procedure) (e.g.: coumadin, warfarin) Patient who stopped long term treatment of acetylsalicylic acid (aspirin) or other anti platelets agents within 10 days prior to the treatment procedure; Patient suspected of Disseminated Intravascular Coagulation (DIC) as defined by the presence of three out of the five following criteria: platelets decrease, increase of PT, increase of aPTT, fibrinogen decrease, D-Dimer increase; from the normal laboratory ranges; Patient with a history of vasculitis or collagen vascular disease; History of non compliance with medical therapy and medical recommendations or an unwillingness or inability to complete patient self-administered questionnaires; Participation in a clinical study or receipt of an investigational treatment within the past 3 months; A history of porphyria; A history of sun hypersensitivity or photosensitive dermatitis; Renal disorders (blood creatinine > 1.5 x ULN) or known post mictional residue > 150cc Hepatic disorders (transaminases > ULN, bilirubin > ULN, GGT > ULN). In case of slight abnormalities, another exam could be performed. If the results are within normal ranges, then the patient can be included; Hematological disorders (white cells < 2500/mm3, neutrophils < 1500/mm3, platelets, < 140.000/mm3, Hb ≤ 10 g/dL); Patients with contra-indication to MRI (such as pace maker, metal prosthesis, etc.).

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: WST11 (TOOKAD® Soluble)<br>WST11-mediated-VTP The WST11-mediated VTP procedure will consist of a single, 10 min, IV administration of WST11 at doses of either 2mg/kg, 4 mg/kg or 6 mg/kg, followed by light activation delivered through one or more transperineal interstitial optical fibers using 753 nm laser light at escalating fixed energy doses | Drug: WST 11 -mediated -VTP<br>* The WST11-mediated VTP procedure will consist of a single, 10 min, IV administration of WST11 at doses of either 2mg/kg, 4 mg/kg or 6 mg/kg, followed by light activation delivered through one or more transperineal interstitial optical fibers for 20 minutes using 753 nm laser light at escalating fixed energy doses of 200 J/cm and 300 J/cm, by escalating power at each energy to 167 mW/cm and 250 mW/cm, respectively. A brachytherapy-like template is used for the placement of the optical fiber(s) that are positioned in the prostate areas of interest under trans-rectal ultrasound image guidance.<br>* Other names: TOOKAD Soluble;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Prostate Biopsy | Arm/Group Title: WST 11(TOOKAD® Soluble) Arm/Group Description To define the study drug and light dosage combination to achieve negative biopsy in the treated lobe | Month 6 | 
| Prostate Biopsies | Number of patients who had a negative biopsy at Month-6 | Month-6 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetic Parameters-Cmax | For each dose group, several pharmacokinetics parameters have been calculated. | T0, 5 min,10 min, 4 h, 8 h, post dose | 
| Percentage of Prostatic Necrosis at Day 7 as Observed on the 7-Day MRI | The adjusted prostate necrosis percentage was defined as follows: The Day 7 necrosis percentage is the proportion, expressed in %, of Day 7 prostate necrosis volume by planimetry in the treated lobe compared with half the prostate volume by planimetry, considering the average between the baseline volume and Day 7 volume; | Day 7 | 
| International Index of Erectile Functions (IIEF) Results | The International Index of Erectile Functions questionnaire is 15 questions patients auto questionnaire. The results presented are those of the erectile function domain which comprise 6 questions. Possible scores range is 1 to 30 . Best score is 30, worst score is 1. | Month 1-Month 3- Month 6- Month 12 | 
| International Prostate Symptom Score (IPSS) Results | The International Prostate Symptom Score (IPSS) is a 7 questions patients auto-questionnaire about urinary symptoms. the possible scores range are 0 to 35 . Best score is 0 worst score is 35 | Month 1, Month 3 , Month 6 , Month 12 | 
| Pharmacokinetic Parameters-Tmax | For each dose group, several pharmacokinetics parameters have been calculated. | T0, 5 min,10 min, 4 h, 8 h, post dose | 
| Pharmacokinetic Parameters -T1/2 | For each dose group, several pharmacokinetics parameters have been calculated. | T0, 5 min,10 min, 4 h, 8 h, post dose | 

 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, Neoplasm by site, prostatic neoplasm, Carcinoma