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

Sponsor

University Hospital Inselspital, Berne (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05024734

Collaborator

University of Bern (Other), Hospital Centre Biel/Bienne (Other)

Enrollment

Location

Arms

46.9

Anticipated Duration (Months)

0.7

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Bladder Cancer Non-muscle Invasive	Drug: Epirubicin Drug: Mitomycin Drug: Gemcitabine Drug: Docetaxel	Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

33 participants

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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)

Anticipated Study Start Date :

Jul 1, 2022

Anticipated Primary Completion Date :

May 30, 2024

Anticipated Study Completion Date :

May 30, 2026

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures

Number of patients with successful drug selection [24 months]
● To determine the proportion of patients for which a suitable treatment can be identified by drug screens in patient derived organoids This will establish the use of drug screens in PDOs in clinical setting and their implementation in clinical trials.

Secondary Outcome Measures

Side effects [24 months]
Number of patients with side effects
Recurrence rate [42 months]
Number of patients with recurrence
QoL [42 months]
Quality of life will be determined using the SF-36 questionnaire

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Roland Seiler	Biel		Switzerland	2501

Sponsors and Collaborators

University Hospital Inselspital, Berne
University of Bern
Hospital Centre Biel/Bienne

Investigators

Study Chair: Roland Seiler, MD, Department of Urology

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

University Hospital Inselspital, Berne

ClinicalTrials.gov Identifier:

NCT05024734

Other Study ID Numbers:

SZB-URO-21-001

First Posted:

Aug 27, 2021

Last Update Posted:

May 17, 2022

Last Verified:

May 1, 2022

Individual Participant Data (IPD) Sharing Statement:

Yes

Plan to Share IPD:

Yes

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Product Manufactured in and Exported from the U.S.:

Additional relevant MeSH terms:

Urinary Bladder Neoplasms

Study Results

No Results Posted as of May 17, 2022