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

NCT05024734 | Recruiting Phase 2 DMC

• 1 other identifier: SZB-URO-21-001
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 1

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.

Conditions

Bladder Cancer; Non-muscle Invasive

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (7)

• 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

  24 months

• Recurrence free survival 24 months after TURBT

  24 months

• Progression free survival 24 months after TURBT

  24 months

• General quality of Life

  24 months

Study Arms (4)

Epirubicin

EXPERIMENTAL

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

Mitomycin

EXPERIMENTAL

Patients in that PDOs show highest response to this drug in-vitro will be treated with Mitomycin.

Drug: Mitomycin

Gemcitabine

EXPERIMENTAL

Patients in that PDOs show highest response to this drug in-vitro will be treated with Gemcitabine.

Drug: Gemcitabine

Docetaxel

EXPERIMENTAL

Patients in that PDOs show highest response to this drug in-vitro will be treated with Docetaxel.

Drug: Docetaxel

Interventions

Epirubicin DRUG

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.

Epirubicin

Mitomycin DRUG

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

Mitomycin

Gemcitabine DRUG

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.

Gemcitabine

Docetaxel DRUG

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.

Docetaxel

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Roland Seiler-Blarer: lead
• University of Bern: collaborator
• Hospital Centre Biel/Bienne: collaborator

Study Sites (1)

Spitalzentrum Biel/Bienne

Biel, 2501, Switzerland

RECRUITING

Related Publications (1)

• Seiler R, Egger M, De Menna M, Wehrli S, Minoli M, Radic M, Lyatoshinsky P, Hosli R, Blarer J, Abt D, Kruithof-de Julio M. 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. BMC Urol. 2023 May 11;23(1):89. doi: 10.1186/s12894-023-01262-1.

  PMID: 37170307 DERIVED

MeSH Terms

Conditions

Urinary Bladder Neoplasms

Interventions

Epirubicin; Mitomycin; Gemcitabine; Docetaxel

Condition Hierarchy (Ancestors)

Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Doxorubicin; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Mitomycins; Indolequinones; Quinones; Azirines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Diterpenes; Terpenes

Study Officials

• Roland Seiler-Blarer, MD

  Department of Urology

  STUDY CHAIR

Central Study Contacts

Roland Seiler-Blarer, MD

CONTACT

+41 32 324 32 06; urologie@szb-chb.ch

Martina Schneider, PhD

CONTACT

+4132 324 32 17; Martina.Schneider@szb-chb.ch

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Chairman

Study Record Dates

• First Submitted: August 23, 2021
• First Posted: August 27, 2021
• Study Start: February 21, 2023
• Primary Completion: October 31, 2025
• Study Completion (Estimated): October 31, 2027
• Last Updated: March 11, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP

Locations

CH (1)