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
Conditions
Interventions
Product Name: AdCD40L
Product Code: AdCD40L
Pharmaceutical Form: Solution for intravesical use
Current Sponsor code: AdCD40L
Concentration type: equal
Concentration number: 1 x 10e12particl.-
Pharmac
Sponsors
Clinical Immunology Division
Eligibility
Sex/Gender
All
Inclusion criteria
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 Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
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 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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 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.;Secondary Objective: 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 ;Primary end point(s): - Registration of the safety profile such as local inflammation, fever, pain, change in blood pressure, pulse and other adverse events. | — |
Countries
Sweden
Outcome results
None listed