Bladder Cancer, Non-muscle Invasive
Conditions
Brief summary
From patients with intermediate risk non-muscle invasive bladder cancer tumor (NMIBC) specimens will be harvested during transurethral resection. Fresh specimens will be cultured as patient derived organoids (PDO). After approx. 10 days, PDO are exposed to different drugs that are used as intravesical instillation agents in these patients (epirubicin, mitomycin, gemcitabine, docetaxel). After 2 days of exposure, PDO viability will be measured. The drug with the highest antitumor effect on PDO will be applied as weekly intravesical instillations 6 times. Thereafter, patients are followed according to the standard of care.
Interventions
DRUGEpirubicin
In PDOs from patients that show highest response to Epirubicin, this drug will be instilled intravesically once weekly for 6 times. Epirubicin is also the default drug, in case of failure of drug prediction in the in-vitro drug screen in PDO. Epirubicin will be used as a concentrate for injection/instillation 2 mg/ml in total 50mg per vial. Prior to use, the concentrate for injection is diluted with 25ml of 0.9% saline solution to obtain the final Solution with 1mg/ml of Epirubicin.
DRUGMitomycin
In PDOs from patients that show highest response to Mitomycin, this drug will be instilled intravesically once weekly for 6 times. Mitomycin C will be used as 20mg dry powder. Prior to use, the powder will be dissolved in 50ml of 0.9% saline solution according to the manufacturer instructions
DRUGGemcitabine
In PDOs from patients that show highest response to Gemcitabine, this drug will be instilled intravesically once weekly for 6 times. Gemcitabine will be used as 2000 mg/50ml. For intravesical application, 1000mg of gemcitabine (corresponding to 25ml) will be diluted in 25ml 0.9% saline solution, to obtain the gemcitabine concentration of 1000mg/50ml used for instillation.
DRUGDocetaxel
In PDOs from patients that show highest response to Docetaxel, this drug will be instilled intravesically once weekly for 6 times. Docetaxel will be used as 140mg/7ml solution. For intravesical application, 48.825ml of saline will be added to 1.875ml Docetaxel solution (according 37.5mg of Docetaxel). The concentration of this solution is 0.74mg/ml by a total volume of the instillation solution of 50,7.
Sponsors
Roland Seiler-Blarer
University of Bern
Hospital Centre Biel/Bienne
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age ≥ 18 years * Signed Informed Consent Form * ECOG performance status of 0 or 1 * Histologically confirmed intermediate risk non muscle-invasive urothelial carcinoma of the bladder (pTa low grade) Patients * Representative fresh tumor specimen for PDO generation and drug screen
Exclusion criteria
* Known previous high grade and/or high risk non muscle-invasive bladder cancer * Previous Intravesical biological/immuno (BCG) therapy * Pregnancy or nursing * Evidence of significant uncontrolled concomitant disease that could affect compliance with the protocol * Severe infection within 4 weeks prior to cycle 1, day 1 * Contraindication for frequent catheterization * Voiding dysfunction * Pregnancy or nursing * Female subject of childbearing potential who is unwilling to use acceptable method(s) of effective contraception during study treatment and through 6 months after the last treatment. * Male subject who is unwilling to use acceptable method of effective contraception during IP treatment and through 6 months after the last dose of IP.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of patients with successful drug selection | 24 months | Proportion of patients for which a specific selection of chemotherapeutic agent for intravesical instillation can be determined by using drug screens in PDOs. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of patients for whom patient-derived organoids (PDOs) can be successfully generated (regardless of subsequent drug screen) | 24 months | Proportion of patients for whom patient-derived organoids (PDOs) can be successfully generated (regardless of subsequent drug screen) |
| Rate of recurrence in the study population | 24 months | Rate of recurrence in the study population |
| Recurrence free survival 24 months after TURBT | 24 months | Proportion of patients that show recurrence 24 months after TURBT |
| Progression free survival 24 months after TURBT | 24 months | Proportion of patients that show progression 24 months after TURBT |
| General quality of Life | 24 months | Description of the general quality of life based on the questionnaire EORTC-QLQ-C30 |
| Quality of Life related to the bladder cancer | 24 months | Description of the Quality of Life related to the bladder cancer based on the specific NMIBC24 module |
| Safety profile of instillations | 24 months | Description of the side effects related to the chemotherapeutic intravesical instillations occuring during the treatment phase. |
Countries
Switzerland
Contacts
STUDY_CHAIRRoland Seiler-Blarer, MD
Department of Urology
Outcome results
None listed