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

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)

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.

Study Overview

• Status: Recruiting
• Conditions: Bladder Cancer; Non-muscle Invasive
• Intervention / Treatment: Drug: Epirubicin; Drug: Mitomycin; Drug: Gemcitabine; Drug: Docetaxel

• Study Type: Interventional
• Enrollment (Estimated): 34
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Roland Seiler-Blarer, MD; Phone Number: +41 32 324 32 06; Email: urologie@szb-chb.ch
• Study Contact Backup: Name: Martina Schneider, PhD; Phone Number: +4132 324 32 17; Email: Martina.Schneider@szb-chb.ch

Study Locations

• Switzerland
  • Biel, Switzerland, 2501
    • Recruiting
    • Spitalzentrum Biel/Bienne
    • Contact: Roland Seiler-Blarer, Prof.; Phone Number: +41 32 324 32 06; Email: r_seiler@gmx.ch
    • Contact: Martina Schneider, PhD; Phone Number: +41 32 324 32 17; Email: Martina.Schneider@szb-chb.ch
    • Contact: Roland Seiler-Blarer, Prof.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	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.
Experimental: Mitomycin; Patients in that PDOs show highest response to this drug in-vitro will be treated with Mitomycin.	Drug: 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
Experimental: Gemcitabine; Patients in that PDOs show highest response to this drug in-vitro will be treated with Gemcitabine.	Drug: 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.
Experimental: Docetaxel; Patients in that PDOs show highest response to this drug in-vitro will be treated with Docetaxel.	Drug: 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of patients with successful drug selection	Proportion of patients for which a specific selection of chemotherapeutic agent for intravesical instillation can be determined by using drug screens in PDOs.	24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of patients for whom patient-derived organoids (PDOs) can be successfully generated (regardless of subsequent drug screen)	Proportion of patients for whom patient-derived organoids (PDOs) can be successfully generated (regardless of subsequent drug screen)	24 months
Rate of recurrence in the study population	Rate of recurrence in the study population	24 months
Recurrence free survival 24 months after TURBT	Proportion of patients that show recurrence 24 months after TURBT	24 months
Progression free survival 24 months after TURBT	Proportion of patients that show progression 24 months after TURBT	24 months
General quality of Life	Description of the general quality of life based on the questionnaire EORTC-QLQ-C30	24 months
Quality of Life related to the bladder cancer	Description of the Quality of Life related to the bladder cancer based on the specific NMIBC24 module	24 months
Safety profile of instillations	Description of the side effects related to the chemotherapeutic intravesical instillations occuring during the treatment phase.	24 months

Collaborators and Investigators

• Sponsor: Roland Seiler-Blarer
• Collaborators: University of Bern; Hospital Centre Biel/Bienne
• Investigators: Study Chair: Roland Seiler-Blarer, MD, Department of Urology

Study record dates

Study Major Dates

• Study Start (Actual): February 21, 2023
• Primary Completion (Estimated): October 31, 2025
• Study Completion (Estimated): October 31, 2027

Study Registration Dates

• First Submitted: August 23, 2021
• First Submitted That Met QC Criteria: August 23, 2021
• First Posted (Actual): August 27, 2021

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: March 7, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Male Urogenital Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Urologic Neoplasms; Carcinoma; Urinary Bladder Diseases; Non-Muscle Invasive Bladder Neoplasms; Urinary Bladder Neoplasms; Antibiotics, Antineoplastic; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Nucleic Acid Synthesis Inhibitors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Topoisomerase Inhibitors; Alkylating Agents; Topoisomerase II Inhibitors; Docetaxel; Gemcitabine; Mitomycins; Mitomycin; Epirubicin
• Other Study ID Numbers: SZB-URO-21-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No