Prostate Cancer
Conditions
Keywords
Prostatic disease, genital neoplasm, male, Urogenital neoplasm, Genital disease, male, Male urogenital disease, Neoplasms, Neoplasm by site, prostatic neoplasm, Carcinoma
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.
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
Interventions
DRUGWST 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.
Sponsors
Steba Biotech S.A.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
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.).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| Prostate Biopsies | Month-6 | Number of patients who had a negative biopsy at Month-6 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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 |
| 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; |
| 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. |
| Pharmacokinetic Parameters-Tmax | T0, 5 min,10 min, 4 h, 8 h, post dose | For each dose group, several pharmacokinetics parameters have been calculated. |
| Pharmacokinetic Parameters-Cmax | T0, 5 min,10 min, 4 h, 8 h, post dose | For each dose group, several pharmacokinetics parameters have been calculated. |
Countries
United States
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.
Participants by arm
| Arm | Count |
|---|---|
| WST 11(TOOKAD® Soluble) 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. | 30 |
| Total | 30 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| First Treatment | Patient relocated to another state | 1 |
| First Treatment | Withdrawal by Subject | 1 |
| Retreatment | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | WST 11(TOOKAD® Soluble) |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 13 Participants |
| Age, Categorical Between 18 and 65 years | 17 Participants |
| Age, Continuous | 61.6 years STANDARD_DEVIATION 7.8 |
| Region of Enrollment United States | 30 participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 30 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 25 / 30 |
| serious Total, serious adverse events | 0 / 30 |
Outcome results
Primary
Prostate Biopsies
Number of patients who had a negative biopsy at Month-6
Time frame: Month-6
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 2 mg/Kg-200 J/cm | Prostate Biopsies | 3 Participants |
| 2 mg/Kg-300 J/cm | Prostate Biopsies | 3 Participants |
| 4 mg/Kg-200 J/cm | Prostate Biopsies | 13 Participants |
| All Doses/Energies | Prostate Biopsies | 19 Participants |
Primary
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
Time frame: Month 6
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 2 mg/Kg-200 J/cm | Prostate Biopsy | Positive | 0 participants |
| 2 mg/Kg-200 J/cm | Prostate Biopsy | Negative | 3 participants |
| 2 mg/Kg-300 J/cm | Prostate Biopsy | Negative | 3 participants |
| 2 mg/Kg-300 J/cm | Prostate Biopsy | Positive | 3 participants |
| 4 mg/Kg-200 J/cm | Prostate Biopsy | Positive | 8 participants |
| 4 mg/Kg-200 J/cm | Prostate Biopsy | Negative | 13 participants |
| All Doses/Energies | Prostate Biopsy | Positive | 11 participants |
| All Doses/Energies | Prostate Biopsy | Negative | 19 participants |
Secondary
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.
Time frame: Month 1-Month 3- Month 6- Month 12
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 2 mg/Kg-200 J/cm | International Index of Erectile Functions (IIEF) Results | Month 3 | 19.33 units on a scale | Standard Deviation 4.04 |
| 2 mg/Kg-200 J/cm | International Index of Erectile Functions (IIEF) Results | Month 12 | 21.67 units on a scale | Standard Deviation 2.52 |
| 2 mg/Kg-200 J/cm | International Index of Erectile Functions (IIEF) Results | Baseline | 21.33 units on a scale | Standard Deviation 4.73 |
| 2 mg/Kg-200 J/cm | International Index of Erectile Functions (IIEF) Results | Month 1 | 14.33 units on a scale | Standard Deviation 10.97 |
| 2 mg/Kg-200 J/cm | International Index of Erectile Functions (IIEF) Results | Month 6 | 19.33 units on a scale | Standard Deviation 1.53 |
| 2 mg/Kg-300 J/cm | International Index of Erectile Functions (IIEF) Results | Month 1 | 14.00 units on a scale | Standard Deviation 8.92 |
| 2 mg/Kg-300 J/cm | International Index of Erectile Functions (IIEF) Results | Month 3 | 14.17 units on a scale | Standard Deviation 10.26 |
| 2 mg/Kg-300 J/cm | International Index of Erectile Functions (IIEF) Results | Month 12 | 6.25 units on a scale | Standard Deviation 10.5 |
| 2 mg/Kg-300 J/cm | International Index of Erectile Functions (IIEF) Results | Baseline | 13.17 units on a scale | Standard Deviation 8.7 |
| 2 mg/Kg-300 J/cm | International Index of Erectile Functions (IIEF) Results | Month 6 | 15.00 units on a scale | Standard Deviation 9.47 |
| 4 mg/Kg-200 J/cm | International Index of Erectile Functions (IIEF) Results | Month 1 | 13.65 units on a scale | Standard Deviation 8.98 |
| 4 mg/Kg-200 J/cm | International Index of Erectile Functions (IIEF) Results | Month 12 | 15.29 units on a scale | Standard Deviation 8.48 |
| 4 mg/Kg-200 J/cm | International Index of Erectile Functions (IIEF) Results | Baseline | 18.80 units on a scale | Standard Deviation 7.88 |
| 4 mg/Kg-200 J/cm | International Index of Erectile Functions (IIEF) Results | Month 3 | 14.84 units on a scale | Standard Deviation 7.91 |
| 4 mg/Kg-200 J/cm | International Index of Erectile Functions (IIEF) Results | Month 6 | 15.29 units on a scale | Standard Deviation 7.46 |
| All Doses/Energies | International Index of Erectile Functions (IIEF) Results | Month 3 | 15.18 units on a scale | Standard Deviation 8.04 |
| All Doses/Energies | International Index of Erectile Functions (IIEF) Results | Month 6 | 15.63 units on a scale | Standard Deviation 7.46 |
| All Doses/Energies | International Index of Erectile Functions (IIEF) Results | Baseline | 17.90 units on a scale | Standard Deviation 7.99 |
| All Doses/Energies | International Index of Erectile Functions (IIEF) Results | Month 1 | 13.79 units on a scale | Standard Deviation 8.8 |
| All Doses/Energies | International Index of Erectile Functions (IIEF) Results | Month 12 | 14.48 units on a scale | Standard Deviation 9.26 |
Secondary
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
Time frame: Month 1, Month 3 , Month 6 , Month 12
Population: IPSS results
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 2 mg/Kg-200 J/cm | International Prostate Symptom Score (IPSS) Results | Month 3 | 4.67 units on a scale | Standard Deviation 5.69 |
| 2 mg/Kg-200 J/cm | International Prostate Symptom Score (IPSS) Results | Baseline | 10.67 units on a scale | Standard Deviation 8.02 |
| 2 mg/Kg-200 J/cm | International Prostate Symptom Score (IPSS) Results | Month 6 | 9.67 units on a scale | Standard Deviation 8.62 |
| 2 mg/Kg-200 J/cm | International Prostate Symptom Score (IPSS) Results | Month 1 | 9.67 units on a scale | Standard Deviation 9.87 |
| 2 mg/Kg-200 J/cm | International Prostate Symptom Score (IPSS) Results | Month 12 | 7.33 units on a scale | Standard Deviation 4.04 |
| 2 mg/Kg-300 J/cm | International Prostate Symptom Score (IPSS) Results | Month 3 | 8.83 units on a scale | Standard Deviation 4.83 |
| 2 mg/Kg-300 J/cm | International Prostate Symptom Score (IPSS) Results | Month 1 | 11.00 units on a scale | Standard Deviation 6 |
| 2 mg/Kg-300 J/cm | International Prostate Symptom Score (IPSS) Results | Month 6 | 8.50 units on a scale | Standard Deviation 4.23 |
| 2 mg/Kg-300 J/cm | International Prostate Symptom Score (IPSS) Results | Baseline | 11.67 units on a scale | Standard Deviation 7.31 |
| 2 mg/Kg-300 J/cm | International Prostate Symptom Score (IPSS) Results | Month 12 | 15.5 units on a scale | Standard Deviation 8.89 |
| 4 mg/Kg-200 J/cm | International Prostate Symptom Score (IPSS) Results | Month 12 | 7.93 units on a scale | Standard Deviation 4.5 |
| 4 mg/Kg-200 J/cm | International Prostate Symptom Score (IPSS) Results | Baseline | 8.65 units on a scale | Standard Deviation 6.82 |
| 4 mg/Kg-200 J/cm | International Prostate Symptom Score (IPSS) Results | Month 1 | 10.62 units on a scale | Standard Deviation 6.34 |
| 4 mg/Kg-200 J/cm | International Prostate Symptom Score (IPSS) Results | Month 3 | 8.00 units on a scale | Standard Deviation 5.36 |
| 4 mg/Kg-200 J/cm | International Prostate Symptom Score (IPSS) Results | Month 6 | 6.71 units on a scale | Standard Deviation 4.8 |
| All Doses/Energies | International Prostate Symptom Score (IPSS) Results | Month 12 | 9.29 units on a scale | Standard Deviation 6.02 |
| All Doses/Energies | International Prostate Symptom Score (IPSS) Results | Month 6 | 7.37 units on a scale | Standard Deviation 5.02 |
| All Doses/Energies | International Prostate Symptom Score (IPSS) Results | Month 1 | 10.60 units on a scale | Standard Deviation 6.38 |
| All Doses/Energies | International Prostate Symptom Score (IPSS) Results | Baseline | 9.48 units on a scale | Standard Deviation 6.88 |
| All Doses/Energies | International Prostate Symptom Score (IPSS) Results | Month 3 | 7.83 units on a scale | Standard Deviation 5.22 |
Secondary
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;
Time frame: Day 7
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 2 mg/Kg-200 J/cm | Percentage of Prostatic Necrosis at Day 7 as Observed on the 7-Day MRI | 46.9 percentage of prostatic necrosis | Standard Deviation 41.6 |
| 2 mg/Kg-300 J/cm | Percentage of Prostatic Necrosis at Day 7 as Observed on the 7-Day MRI | 13.8 percentage of prostatic necrosis | Standard Deviation 16.3 |
| 4 mg/Kg-200 J/cm | Percentage of Prostatic Necrosis at Day 7 as Observed on the 7-Day MRI | 61.1 percentage of prostatic necrosis | Standard Deviation 25.3 |
| All Doses/Energies | Percentage of Prostatic Necrosis at Day 7 as Observed on the 7-Day MRI | 52.3 percentage of prostatic necrosis | Standard Deviation 31.9 |
Secondary
Pharmacokinetic Parameters-Cmax
For each dose group, several pharmacokinetics parameters have been calculated.
Time frame: T0, 5 min,10 min, 4 h, 8 h, post dose
Population: Out of 30 patients treated in the study, 29 patients had pharmacokinetic data available.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 2 mg/Kg-200 J/cm | Pharmacokinetic Parameters-Cmax | 30883.83 ng/mL | Standard Deviation 11583.07 |
| 2 mg/Kg-300 J/cm | Pharmacokinetic Parameters-Cmax | 57102.87 ng/mL | Standard Deviation 14849.5 |
Secondary
Pharmacokinetic Parameters -T1/2
For each dose group, several pharmacokinetics parameters have been calculated.
Time frame: T0, 5 min,10 min, 4 h, 8 h, post dose
Population: Out of 30 patients treated in the study, 29 patients had pharmacokinetic data available.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 2 mg/Kg-200 J/cm | Pharmacokinetic Parameters -T1/2 | 1.25 hours | Standard Deviation 0.9 |
| 2 mg/Kg-300 J/cm | Pharmacokinetic Parameters -T1/2 | 1.69 hours | Standard Deviation 1.11 |
Secondary
Pharmacokinetic Parameters-Tmax
For each dose group, several pharmacokinetics parameters have been calculated.
Time frame: T0, 5 min,10 min, 4 h, 8 h, post dose
Population: Out of 30 patients treated in the study, 29 patients had pharmacokinetic data available.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 2 mg/Kg-200 J/cm | Pharmacokinetic Parameters-Tmax | 0.43 hours | Standard Deviation 0.61 |
| 2 mg/Kg-300 J/cm | Pharmacokinetic Parameters-Tmax | 0.25 hours | Standard Deviation 0.22 |