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

NCT ID: NCT05024734

Last Updated: 2025-03-11

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 34 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-02-21
• Study Completion Date: 2027-10-31

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Epirubicin

Intervention Type: 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.

Mitomycin

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

Group Type: EXPERIMENTAL

Mitomycin

Intervention Type: 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

Gemcitabine

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

Group Type: EXPERIMENTAL

Gemcitabine

Intervention Type: 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.

Docetaxel

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

Group Type: EXPERIMENTAL

Docetaxel

Intervention Type: 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.

Interventions

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.

Intervention Type: 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

Intervention Type: 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.

Intervention Type: 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.

Intervention Type: DRUG

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Bern

OTHER

Sponsor Role: collaborator

Hospital Centre Biel/Bienne

OTHER

Sponsor Role: collaborator

Roland Seiler-Blarer

OTHER

Sponsor Role: lead

Responsible Party

Roland Seiler-Blarer

Chairman

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Roland Seiler-Blarer, MD

Role: STUDY_CHAIR

Department of Urology

Locations

Spitalzentrum Biel/Bienne

Biel, , Switzerland

Site Status: RECRUITING

Countries

Switzerland

Central Contacts

Roland Seiler-Blarer, MD

Role: CONTACT

urologie@szb-chb.ch

+41 32 324 32 06

Martina Schneider, PhD

Role: CONTACT

Martina.Schneider@szb-chb.ch

+4132 324 32 17

Facility Contacts

Roland Seiler-Blarer, Prof.

Role: primary

r_seiler@gmx.ch

+41 32 324 32 06

Martina Schneider, PhD

Role: backup

Martina.Schneider@szb-chb.ch

+41 32 324 32 17

References

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.

Reference Type: DERIVED

PMID: 37170307 (View on PubMed)

Other Identifiers

SZB-URO-21-001

Identifier Type: -

Identifier Source: org_study_id