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

• Sponsor: Steba Biotech S.A. (Other)
• Overall Status: Completed
• CT.gov ID: NCT00946881
• Collaborator: (none)
• Enrollment: 30
• Locations: 5
• Arm: 1
• Duration (Months): 37
• Patients Per Site: 6
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Prostate Cancer	Drug: WST 11 -mediated -VTP	Phase 1/Phase 2

Detailed Description

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

Study Design

• Study Type: Interventional
• Actual Enrollment: 30 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Prospective, Multicenter Phase I/II Safety and Tolerability Study of Unilateral Vascular-Targeted Photodynamic Therapy Using WST11 in Patients With Localized Prostate Cancer
• Study Start Date: Jul 1, 2009
• Actual Primary Completion Date: Jul 1, 2012
• Actual Study Completion Date: Aug 1, 2012

Arms and Interventions

Arm

Intervention/Treatment

Experimental: WST11 (TOOKAD® Soluble) 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; 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.; Other Names: TOOKAD Soluble

Outcome Measures

Primary Outcome Measures

1. Prostate Biopsy [Month 6]

   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

2. Prostate Biopsies [Month-6]

   Number of patients who had a negative biopsy at Month-6

Secondary Outcome Measures

1. Pharmacokinetic Parameters-Cmax [T0, 5 min,10 min, 4 h, 8 h, post dose]

   For each dose group, several pharmacokinetics parameters have been calculated.

2. Percentage of Prostatic Necrosis at Day 7 as Observed on the 7-Day MRI [Day 7]

   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;

3. International Index of Erectile Functions (IIEF) Results [Month 1-Month 3- Month 6- Month 12]

   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.

4. International Prostate Symptom Score (IPSS) Results [Month 1, Month 3 , Month 6 , Month 12]

   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

5. Pharmacokinetic Parameters-Tmax [T0, 5 min,10 min, 4 h, 8 h, post dose]

   For each dose group, several pharmacokinetics parameters have been calculated.

6. Pharmacokinetic Parameters -T1/2 [T0, 5 min,10 min, 4 h, 8 h, post dose]

   For each dose group, several pharmacokinetics parameters have been calculated.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

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.).

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	UCLA - Jonsson Comprehensive Cancer Center	Los Angeles	California	United States	90095
2	Midtown Urology & Midtown Urology Surgical Center	Atlanta	Georgia	United States	30308
3	Washington University School of Medicine- Barnes-Jewish Hospital	Saint Louis	Missouri	United States	63110
4	NYU Urology Associates	New York	New York	United States	10016
5	Memorial Sloan-Kettering Cancer Center	New York	New York	United States	10021

Sponsors and Collaborators

• Steba Biotech S.A.

Investigators

• Principal Investigator: Samir Taneja, Professor, Department of Urology, New York University Cancer Institute

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Steba Biotech S.A.
• ClinicalTrials.gov Identifier: NCT00946881
• Other Study ID Numbers: CLIN901 PCM202
• First Posted: Jul 27, 2009
• Last Update Posted: Feb 12, 2019
• Last Verified: Oct 1, 2017

• Individual Participant Data (IPD) Sharing Statement: Undecided
• Plan to Share IPD: Undecided
• Keywords provided by Steba Biotech S.A.: Prostatic disease; genital neoplasm, male; Urogenital neoplasm; Genital disease; male; Male urogenital disease; Neoplasms; Neoplasm by site; prostatic neoplasm; Carcinoma
• Additional relevant MeSH terms: Prostatic Neoplasms

Study Results

Participant Flow

Recruitment Details	Thirty patients were included in the study by five different centers in the US. All 30 patients received the entire VTP procedure (first treatment phase). Two of them discontinued the study prior to Month 12. Eight patients who had positive biopsies at Month 6 entered in the retreatment phase. Only 7 of them actually received retreatment.

Arm/Group Title	WST 11(TOOKAD® Soluble)
Arm/Group Description	WST 11-mediated-VTP WST 11 -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 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.
Period Title: First Treatment
STARTED	30
COMPLETED	28
NOT COMPLETED	2
Period Title: First Treatment
STARTED	8
COMPLETED	7
NOT COMPLETED	1

Baseline Characteristics

Arm/Group Title	WST 11(TOOKAD® Soluble)
Arm/Group Description	WST 11-mediated-VTP WST 11 -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 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.
Overall Participants	30
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	17 56.7%
>=65 years	13 43.3%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	61.6 (7.8)
Sex: Female, Male (Count of Participants)
Female	0 0%
Male	30 100%
Region of Enrollment (participants) [Number]
United States	30 100%

Outcome Measures

1. Primary Outcome

Title	Prostate Biopsy
Description	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
Time Frame	Month 6

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	2 mg/Kg-200 J/cm	2 mg/Kg-300 J/cm	4 mg/Kg-200 J/cm	All Doses/Energies
Arm/Group Description	Number of patients with positives or négatives biopsies at the dose 2mg/Kg-200J/cm	Number of patients with positives or négatives biopsies at the dose 2mg/Kg-300J/cm	Number of patients with positives or négatives biopsies at the dose 4mg/Kg-200J/cm	Number of patients with positives or négatives biopsies at all doses/energies
Measure Participants	3	6	21	30
Positive	0 0%	3 NaN	8 NaN	11 NaN
Negative	3 10%	3 NaN	13 NaN	19 NaN

2. Primary Outcome

Title	Prostate Biopsies
Description	Number of patients who had a negative biopsy at Month-6
Time Frame	Month-6

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	2 mg/Kg-200 J/cm	2 mg/Kg-300 J/cm	4 mg/Kg-200 J/cm	All Doses/Energies
Arm/Group Description	Number of patients with negative biopsies at the dose 2mg/Kg-200J/cm	Number of patients with negative biopsies at the dose 2mg/Kg-300J/cm	Number of patients with negative biopsies at the dose 4mg/Kg-200J/cm	Number of patients with negative biopsies at all doses/energies
Measure Participants	3	6	21	30
Count of Participants [Participants]	3 10%	3 NaN	13 NaN	19 NaN

3. Secondary Outcome

Title	Pharmacokinetic Parameters-Cmax
Description	For each dose group, several pharmacokinetics parameters have been calculated.
Time Frame	T0, 5 min,10 min, 4 h, 8 h, post dose

Outcome Measure Data

Analysis Population Description

Out of 30 patients treated in the study, 29 patients had pharmacokinetic data available.

Arm/Group Title	2 mg/kg	4 mg/kg
Arm/Group Description	Patients treated at the dose of 2 mg/kg of TOOKAD soluble, regardless of the dose of light, are analysed in this group.	Patients treated at the dose of 4 mg/kg of TOOKAD soluble, regardless of the dose of light, are analysed in this group.
Measure Participants	9	20
Mean (Standard Deviation) [ng/mL]	30883.83 (11583.07)	57102.87 (14849.50)

4. Secondary Outcome

Title	Percentage of Prostatic Necrosis at Day 7 as Observed on the 7-Day MRI
Description	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;
Time Frame	Day 7

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	2 mg/Kg-200 J/cm	2 mg/Kg-300 J/cm	4 mg/Kg-200 J/cm	All Doses/Energies
Arm/Group Description	To evaluate the volume of necrosis observed on the 7-Day MRI in patients treated with 2 mg/kg-200J/cm	To evaluate the volume of necrosis observed on the 7-Day MRI in patients treated with 2 mg/kg-300J/cm	To evaluate the volume of necrosis observed on the 7-Day MRI in patients treated with 4 mg/kg-200J/cm	To evaluate the volume of necrosis observed on the 7-Day MRI in patients treated with all doses/energies
Measure Participants	3	6	21	30
Mean (Standard Deviation) [percentage of prostatic necrosis]	46.9 (41.6)	13.8 (16.3)	61.1 (25.3)	52.3 (31.9)

5. Secondary Outcome

Title	International Index of Erectile Functions (IIEF) Results
Description	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.
Time Frame	Month 1-Month 3- Month 6- Month 12

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	2 mg/Kg-200 J/cm	2 mg/Kg-300 J/cm	4 mg/Kg-200 J/cm	All Doses/Energies
Arm/Group Description	To assess the QoL-IIEF in patients treated with the dose 2mg/Kg-200J/cm	To assess the QoL-IIEF in patients treated with the dose 2mg/Kg-300J/cm	To assess the QoL-IIEF in patients treated with the dose 4mg/Kg-200J/cm	To assess the QoL-IIEF in patients treated with all doses/energies
Measure Participants	3	6	21	30
Baseline	21.33 (4.73)	13.17 (8.70)	18.80 (7.88)	17.90 (7.99)
Month 1	14.33 (10.97)	14.00 (8.92)	13.65 (8.98)	13.79 (8.80)
Month 3	19.33 (4.04)	14.17 (10.26)	14.84 (7.91)	15.18 (8.04)
Month 6	19.33 (1.53)	15.00 (9.47)	15.29 (7.46)	15.63 (7.46)
Month 12	21.67 (2.52)	6.25 (10.50)	15.29 (8.48)	14.48 (9.26)

6. Secondary Outcome

Title	International Prostate Symptom Score (IPSS) Results
Description	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
Time Frame	Month 1, Month 3 , Month 6 , Month 12

Outcome Measure Data

Analysis Population Description

IPSS results

Arm/Group Title	2 mg/Kg-200 J/cm	2 mg/Kg-300 J/cm	4 mg/Kg-200 J/cm	All Doses/Energies
Arm/Group Description	To assess the QoL-IPSS in patients treated with the dose 2mg/Kg-200J/cm	To assess the QoL-IPSS in patients treated with the dose 2mg/Kg-300J/cm	To assess the QoL-IPSS in patients treated with the dose 4mg/Kg-200J/cm	To assess the QoL-IPSS in patients treated with all doses/energies
Measure Participants	3	6	21	30
Baseline	10.67 (8.02)	11.67 (7.31)	8.65 (6.82)	9.48 (6.88)
Month 1	9.67 (9.87)	11.00 (6.00)	10.62 (6.34)	10.60 (6.38)
Month 3	4.67 (5.69)	8.83 (4.83)	8.00 (5.36)	7.83 (5.22)
Month 6	9.67 (8.62)	8.50 (4.23)	6.71 (4.80)	7.37 (5.02)
Month 12	7.33 (4.04)	15.5 (8.89)	7.93 (4.50)	9.29 (6.02)

7. Secondary Outcome

Title	Pharmacokinetic Parameters-Tmax
Description	For each dose group, several pharmacokinetics parameters have been calculated.
Time Frame	T0, 5 min,10 min, 4 h, 8 h, post dose

Outcome Measure Data

Analysis Population Description

Out of 30 patients treated in the study, 29 patients had pharmacokinetic data available.

Arm/Group Title	2 mg/kg	4 mg/kg
Arm/Group Description	Patients treated at the dose of 2 mg/kg of TOOKAD soluble, regardless of the dose of light, are analysed in this group.	Patients treated at the dose of 4 mg/kg of TOOKAD soluble, regardless of the dose of light, are analysed in this group.
Measure Participants	9	20
Mean (Standard Deviation) [hours]	0.43 (0.61)	0.25 (0.22)

8. Secondary Outcome

Title	Pharmacokinetic Parameters -T1/2
Description	For each dose group, several pharmacokinetics parameters have been calculated.
Time Frame	T0, 5 min,10 min, 4 h, 8 h, post dose

Outcome Measure Data

Analysis Population Description

Out of 30 patients treated in the study, 29 patients had pharmacokinetic data available.

Arm/Group Title	2 mg/kg	4 mg/kg
Arm/Group Description	Patients treated at the dose of 2 mg/kg of TOOKAD soluble, regardless of the dose of light, are analysed in this group.	Patients treated at the dose of 4 mg/kg of TOOKAD soluble, regardless of the dose of light, are analysed in this group.
Measure Participants	9	20
Mean (Standard Deviation) [hours]	1.25 (0.90)	1.69 (1.11)

Adverse Events

Time Frame	1 year
Arm/Group Title	WST 11(TOOKAD® Soluble)
Arm/Group Description	WST 11-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 WST 11 -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 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.
All Cause Mortality
	WST 11(TOOKAD® Soluble)
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	WST 11(TOOKAD® Soluble)
	Affected / at Risk (%)	# Events
Total	0/30 (0%)
Other (Not Including Serious) Adverse Events
	WST 11(TOOKAD® Soluble)
	Affected / at Risk (%)	# Events
Total	25/30 (83.3%)
Gastrointestinal disorders
Gastrointestinal disorder	9/30 (30%)	10
General disorders
General disorders	5/30 (16.7%)	5
Injury, poisoning and procedural complications
Injury, poisoning	3/30 (10%)	3
Investigations
Investigations	9/30 (30%)	12
Musculoskeletal and connective tissue disorders
Musculoskeletal disorders	5/30 (16.7%)	6
Nervous system disorders
Nervous system disorders	2/30 (6.7%)	2
Renal and urinary disorders
Renal and urinary disorders	19/30 (63.3%)	45
Reproductive system and breast disorders
Reproductive system and breast disorders	16/30 (53.3%)	25
Respiratory, thoracic and mediastinal disorders
Respiratory, thoracic and mediastinal disorders	2/30 (6.7%)	2
Skin and subcutaneous tissue disorders
Skin disorders	5/30 (16.7%)	5
Vascular disorders
Vascular disorders	2/30 (6.7%)	2

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.