E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Urinary bladder cancer is an attractive target for immunostimulating gene therapy because it is sensitive for immunotherapy as demonstrated by the life-prolonging effect of bacillus Calmette-Guérin (BCG) instillations. Phase I: Patients with infiltrative cancer of the urinary bladder and scheduled for cystectomy. Phase IIa: Patients with non-infiltrative cancer of the urinary bladder, stages Ta and scheduled for resection
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MedDRA Classification |
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 |
Part I To evaluate the feasibility of local treatment of bladder cancer at two dose levels and, if possible, establish the Maximum Tolerable Dose (MTD) by studying the tolerance and toxicity in patients scheduled for cystectomy, during and after repeated instillations of Clorpactin and AdCD40L in the urinary bladder. Part IIa Confirm tolerance/toxicity of repeated instillations of Clorpactin and AdCD40L at the highest dose OR the next lower dose to MTD, in the urinary bladder of patients with marker tumour. |
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E.2.2 | Secondary objectives of the trial |
Part I - Establish the AdCD40L dose that demonstrates transgene (CD40L) expression in the bladder wall - Assure that there is no systemic exposure toAdCD40L. - Elimination time of AdCD40L in urine post treatment - Change of the immune profile due to virus vector exposure and transgene expression - Tumour response - Establish the baseline symptoms of Clorpactin installation during run-in - Biological activity Part IIa - Tumour response - Investigate the transgene (CD40L) expression in the bladder wall - Assure that there is no systemic exposure toAdCD40L - Elimination time of AdCD40L in urine post treatment - Change of the immune profile due to virus vector exposure and transgene expression - Biological activity
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
1. ECOG 0-2 (Appendix 1.4). 2. Male or females, 18 years of age or older. 3. Signed informed consent must be obtained. Patients in the phase I part of the study should also meet the criteria: 4. Histological proven diagnosis of transitional cell carcinoma of the bladder, scheduled for cystectomy.
Patients in the phase IIa part of the study should also meet the following criteria: 5. Histological proven diagnosis of Ta, recurrent transitional cell carcinoma of the bladder. 6. Evaluable disease confirmed by positive biopsy histology
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E.4 | Principal exclusion criteria |
7. Woman of childbearing potential (fertile woman). 8. Other malignancy within 5 years of study, except for non-melanoma skin cancer. 9. Metastatic disease. 10. Previous exposure to any intravesical therapy for bladder cancer: within 3 months for chemotherapy and within 6 months for BCG therapy. 11. Previous pelvic radiation or treatment with any cytotoxic, immunologic or chemotherapeutic agent for non-malignant conditions within 5 years of study. 12. Clinically abnormal hepatic, renal or bone marrow function, or coagulation disorders in the opinion of the investigator. 13. Chronic urinary tract infections. 14. Serious infection or G.U. surgery within 1 month of study requiring more than 3 days of hospital care. 15. Vesical capacity <150 mL and/or vesical obstruction with residual >100 mL after spontaneous voiding. 16. Previous exposure to any experimental drug within 3 months from enrolment. 17. Any significant medical or psychiatric illness that would prevent the patient from giving informed consent or from following the study procedures. 18. Patients who presently have transitional cell carcinoma of the upper tract and/or disease 19. Patients with systemic autoimmune disease. 20. Patients that do not consent to that tissue and blood samples are stored in a biobank. 21. Treatment with systemically administered corticosteroids and NSAID within 4 weeks prior to first study treatment.
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E.5 End points |
E.5.1 | Primary end point(s) |
- Registration of the safety profile such as local inflammation, fever, pain, change in blood pressure, pulse and other adverse events. |
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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 | Yes |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
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) | Yes |
E.7.1.1 | First administration to humans | Yes |
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 | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
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 | 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 | No |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
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 | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
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 | 3 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |