Guiding Instillation in Non Muscle-invasive Bladder Cancer Based on Drug Screens in Patient Derived Organoids

Bladder Cancer Clinical Trial

Official title:

Guidance of Adjuvant Instillation in Intermediate Risk Non-muscle Invasive Bladder Cancer by Drug Screens in Patient Derived Organoids. A Single Center, Open-label, Phase II Trial With a Feasibility Endpoint. (GAIN-INST-TRIAL)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05024734
• Other study ID #: SZB-URO-21-001
• Status: Recruiting
• Phase: Phase 2
• Start date: November 17, 2022
• Est. completion date: November 16, 2026

Study information

• Verified date: November 2022
• Source: University Hospital Inselspital, Berne
• Contact: Roland Seiler, MD
• Phone: +4132 324 32 06
• Email: urologie[@]szb-chb.ch
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 33
• Est. completion date: November 16, 2026
• Est. primary completion date: November 16, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Bladder Cancer
• Urinary Bladder Neoplasms

Intervention

Drug:
• Epirubicin
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.
• Mitomycin
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
• Gemcitabine
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.
• Docetaxel
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.

Locations

Country	Name	City	State
Switzerland	Roland Seiler	Biel

Sponsors (3)

Lead Sponsor	Collaborator
University Hospital Inselspital, Berne	Hospital Centre Biel/Bienne, University of Bern

Country where clinical trial is conducted

Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of patients with successful drug selection	? To determine the proportion of patients for which a suitable treatment can be identified by drug screens in patient derived organoids This will establish the use of drug screens in PDOs in clinical setting and their implementation in clinical trials.	24 months
Secondary	Side effects	Number of patients with side effects	24 months
Secondary	Recurrence rate	Number of patients with recurrence	42 months
Secondary	QoL	Quality of life will be determined using the SF-36 questionnaire	42 months