E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Suspected non-muscle invasive (superficial) bladder cancer |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Diagnosis [E01] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 17.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10005003 |
E.1.2 | Term | Bladder 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 collect preliminary data on the diagnostic performance of Hypericin-guided cystoscopy regarding the detection of non-muscle invasive bladder cancer . Standard, white light cystoscopy will be compared with Hypericin assisted cystoscopy (PVP-Hypericin instillation; white light followed by blue light (Hypericin PDD)) using a within-patient design by inspecting the bladder under white light first, followed by blue light. |
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E.2.2 | Secondary objectives of the trial |
• Diagnostic performance regarding flat and papillary tumours
• False-positive rate
• To evaluate systemic absorption and pharmacokinetics (PK) of Hypericin after a single intravesical instillation of PVP-Hypericin in a sub-group of patients (N=15-20)
• To assess the safety of PVP-Hypericin.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Patients who have given their signed declaration of consent and data protection declaration
2. Males and females aged ≥ 18 years
3. Patients scheduled for transurethral resection of the bladder of a suspected bladder cancer based on recent findings in cystoscopy that have to be diagnosed at the respective study site prior to Visit 1
4. Patients including multiple bladder tumours or suspicious lesions
5. Patients with initial and/or recurrent bladder cancer
6. Patients with adequate renal and hepatic function according to the investigator
7. No known anaesthetic risks (risk of narcosis ASA 1-3)
8. All women of child-bearing potential must have a negative serum or urine pregnancy test at screening and must use hormonal contraception or intrauterine device (IUD) during the treatment and for at least one month thereafter.
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E.4 | Principal exclusion criteria |
1. Intravesical BCG (Bacillus Calmette-Guérin) instillation ≤ 6 months
2. Intravesical Mitomycin instillation ≤ 3 months
3. Patients at high risk of suffering extensive bladder inflammation
4. Recent bladder surgery (resection) ≤ 3 months
5. Patients with symptoms and signs of urinary tract infection, e.g. moderate or severe leukocyturia, dysuria, alguria, urgency, frequency, polyuria, offensive urine, cloudy urine, significant bacteriuria (≥ 100000 CFU/mL), positive urine culture, asymptomatic bacteriuria, suprapubic tenderness, pain or pressure, flank or back pain, fever ≥ 38°C, costovertebral angle tenderness
6. Macroscopic hematuria
7. Bladder stones
8. Bladder capacity ≤ 50 mL
9. Administration of any other photosensitiser < 6 months
10. Oral intake of any drug or substance containing Hypericum extract, Hypericin, Pseudohypericin or parts of Hypericum plants (capsules, tablets, powder, drops, teas, etc.) within 14 days prior to PDD, during the study and until Visit 4 for patients included in the PK subgroup
11. All anticoagulation therapy except low dose heparin and aspirin
12. Known allergy to Hypericin, polyvinylpyrrolidone (PVP, povidone) or any similar compounds
13. Pregnant or breast-feeding women
14. Participation in other clinical studies with investigational drugs either concurrently or within the last 30 days
15. Previous participation in this clinical study
16. Conditions associated with a risk of poor protocol compliance
17. Patients with mental health problems
18. Patients who have difficulties in understanding the language in which the patient information is given
19. Legal incapacity and/or other circumstances rendering the patient unable to understand the nature, scope and possible impact of the study
20. Patients in custody by juridical or official order
21. Staff of the study centre, staff of the sponsor or CRO, the investigator him-/herself or close relatives of the investigator
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E.5 End points |
E.5.1 | Primary end point(s) |
The percentage of patients in whom non-muscle invasive bladder cancer (Tis and / or TaT1) is detected by Hypericin cystoscopy (PVP-Hypericin instillation; white light followed by blue light) as confirmed by biopsy results. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
• The primary endpoint variable for Tis and TaT1 separately (on patient and lesion level)
• False-positive rate
• Systemic absorption and pharmacokinetics of Hypericin after a single-dose intravesical PVP-Hypericin (sub-group analysis)
• Frequency and severity of systemic and local adverse events (AE)
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Yes |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | No |
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 | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
within-patient comparison |
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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 |
white light detection, standard of diagnosis |
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E.8.2.4 | Number of treatment arms in the trial | 1 |
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 | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 12 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 0 |
E.8.9.1 | In the Member State concerned months | 37 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 37 |
E.8.9.2 | In all countries concerned by the trial days | 0 |