Guiding Instillation in Non Muscle-invasive Bladder Cancer Based on Drug Screens in Patient Derived Organoids
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)
Roland Seiler-Blarer
34 participants
Feb 21, 2023
INTERVENTIONAL
Conditions
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.
Eligibility
Inclusion Criteria5
- 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 Criteria10
- 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.
Interventions
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.
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
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.
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(1)
View Full Details on ClinicalTrials.gov
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NCT05024734