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

Phase 2

Recruiting

• Conditions: Bladder Cancer; Non-muscle Invasive
• Interventions: Drug: Mitomycin; Drug: Epirubicin; Drug: Gemcitabine; Drug: Docetaxel

• Registration Number: NCT05024734
• Lead Sponsor: Roland Seiler-Blarer

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2021-08-23
• Study First Submitted QC: 2021-08-23
• Study First Posted: 2021-08-27
• Study Start: 2023-02-21
• Status Verified: 2025-03
• Last Update Submitted: 2025-03-07
• Last Update Posted: 2025-03-11
• Primary Completion: 2025-10-31
• Study Completion: 2027-10-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 34

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Mitomycin	Mitomycin	Patients in that PDOs show highest response to this drug in-vitro will be treated with Mitomycin.
Epirubicin	Epirubicin	Patients in that PDOs show highest response to this drug in-vitro will be treated with Epirubicin. If no significant drug selection can be performed in-vitro, Epirubicin will be the default for instillation.
Gemcitabine	Gemcitabine	Patients in that PDOs show highest response to this drug in-vitro will be treated with Gemcitabine.
Docetaxel	Docetaxel	Patients in that PDOs show highest response to this drug in-vitro will be treated with Docetaxel.

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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)
Recurrence free survival 24 months after TURBT	24 months	Proportion of patients that show recurrence 24 months after TURBT
Rate of recurrence in the study population	24 months	Rate of recurrence in the study population
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.

Trial Locations

Locations (1)

Spitalzentrum Biel/Bienne; 🇨🇭 Biel, Switzerland