E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Localised prostate cancer |
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E.1.1.1 | Medical condition in easily understood language |
Prostate cancer that has not spread |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10060862 |
E.1.2 | Term | Prostate cancer |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To assess the impact of TOOKAD® Soluble VTP on the rate of absence of definite cancer using patients on active surveillance as a comparison (co-primary objective A).
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). |
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E.2.2 | Secondary objectives of the trial |
To determine the differences between men who undergo TOOKAD® Soluble VTP and men on active surveillance with regard to:
• the rate of additional prostate cancer radical therapy
• the total cancer burden in the prostate
• the rate of adverse events
• the rate of incontinence, erectile dysfunction, urinary symptoms
• the rate of severe prostate cancer related events: cance extension to T3, metastasis and prostate cancer related death.
The overall quality of life will be recorded for potential utility and descriptive studies.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1) Low risk prostate cancer diagnosed using one transrectal ultrasound guided biopsy (TRUS) using from 10 to 24 cores, within 12 months of enrolment, and showing the following:
• Gleason 3 + 3 prostate adenocarcinoma as a maximum,
• Two (2) to three (3) cores positive for cancer. Patients with only one positive core can be included provided they have at least 3 mm of cancer core length.
• A maximum cancer core length of 5 mm in any core;
2) Cancer clinical stage up to T2a (pathological or radiological up to T2c disease permitted);
3) Serum prostate specific antigen (PSA) of 10 ng/mL or less;
4) Prostate volume equal or greater than 25 cc and less than 70 cc;
5) Male subjects aged 18 years or older.
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E.4 | Principal exclusion criteria |
1) Unwillingness to accept randomisation to either of the two arms of the study.
2) Any prior or current treatment for prostate cancer, including surgery, radiation therapy (external or brachytherapy) or chemotherapy.
3) Any surgical intervention for benign prostatic hypertrophy.
4) Life expectancy less than 10 years.
5) Any condition or history of illness or surgery that may pose an additional risk to men undergoing the VTP procedure.
6) Participation in another clinical study or recipient of an investigational product within 1 month of study entry.
7) Subject unable to understand the patient's information document, to give consent or complete study tasks. Subject in custody or in residence in a nursing home or rehabilitation facility.
8) Contra-indication to MRI (e.g., pacemaker, history of allergic reaction to gadolinium), or factors excluding accurate reading of pelvic MRI (e.g., hip prosthesis). |
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E.5 End points |
E.5.1 | Primary end point(s) |
Co-primary endpoint 'A'
Absence of any histological result definitely positive for cancer.
Co-primary endpoint 'B'
Failure of treatment due to progression of cancer from low to moderate or higher risk over the 24 month follow-up. 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 any metastasis;
• or prostate cancer related death.
Histological changes are assessed at 12 and 24 months using from 10 to 24 cores TRUS biopsies, with the same number and distribution of core samples per zone used for the initial biopsy at study entry or 1 core per 2 cc of tissue in case of significant prostate shrinkage, or any other pathology result obtained during the study planned or not. The follow-up is done up to loss to follow-up, early study termination or 24 months after randomisation, whatever the treatment events occurring (drop-out, radical treatment). A panel blinded to the exposure status reviews the histological reports of all patients, whether reported positive or negative for cancer, and all the PSA data.
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Histological changes are assessed at 12 and 24 months using from 10 to 24 cores TRUS biopsies, with the same number and distribution of core samples per zone used for the initial biopsy at study entry or 1 core per 2 cc of tissue in case of significant prostate shrinkage, or any other pathology result obtained during the study planned or not. The follow-up is done up to loss to follow up, early study termination or 24 months after randomisation, whatever the treatment events occurring (drop-out, radical treatment). |
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E.5.2 | Secondary end point(s) |
• Notification of initiation of radical therapy
• Total number of cores positive for cancer
• Patients' reported outcome measures (PROMs) impairment: urinary
symptoms, erectile functions
• Adverse event reporting
• Severe prostate cancer related events: cancer extension to T3,
metastasis or prostate cancer-related death.
Quality of life will also be described. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
• Notification of initiation of radical therapy (Over 24 months follow-up)
• Total number of cores positive for cancer (Month 12 and 24)
• Patients' reported outcome measures (PROMs) impairment: urinary
symptoms, erectile functions (Randomisation visit, Day 7 after VTP ,
Month 3, Month 6, Month 9, Month 12, Month 24)
• Adverse event reporting (Screening-Month 24)
• Severe prostate cancer related events: cancer extension to T3,
metastasis or prostate cancer-related death (Screening-Month 24)
Quality of life will also be described. (Randomisation visit; Month 12;
Month 24) |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
Active surveillance population |
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E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 59 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Belgium |
Denmark |
Finland |
France |
Germany |
Italy |
Netherlands |
Spain |
Sweden |
Switzerland |
United Kingdom |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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The definition of the end of trial for Regulatory reporting (Global End of Trial, Clinical Study Report, Pharmacovigilance and DSURs) is defined as per the main protocol; the last visit of the last subject for study relates tests and procedures.
The completion of the Follow –up (addendum) to the main study will be 5 years after the completion of the LPLV of the main study.
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |