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

Primary Purpose

Bladder Cancer, Non-muscle Invasive

Status
Recruiting
Phase
Phase 2
Locations
Switzerland
Study Type
Interventional
Intervention
Epirubicin
Mitomycin
Gemcitabine
Docetaxel
Sponsored by
Insel Gruppe AG, University Hospital Bern
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Bladder Cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept 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

Sites / Locations

  • Roland SeilerRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

Experimental

Experimental

Arm Label

Epirubicin

Mitomycin

Gemcitabine

Docetaxel

Arm Description

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.

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

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

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

Outcomes

Primary Outcome Measures

Number of patients with successful drug selection
● 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
Number of patients with side effects
Recurrence rate
Number of patients with recurrence
QoL
Quality of life will be determined using the SF-36 questionnaire

Full Information

First Posted
August 23, 2021
Last Updated
November 17, 2022
Sponsor
Insel Gruppe AG, University Hospital Bern
Collaborators
University of Bern, Hospital Centre Biel/Bienne
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1. Study Identification

Unique Protocol Identification Number
NCT05024734
Brief Title
Guiding Instillation in Non Muscle-invasive Bladder Cancer Based on Drug Screens in Patient Derived Organoids
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)
Study Type
Interventional

2. Study Status

Record Verification Date
November 2022
Overall Recruitment Status
Recruiting
Study Start Date
November 17, 2022 (Actual)
Primary Completion Date
November 16, 2024 (Anticipated)
Study Completion Date
November 16, 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Insel Gruppe AG, University Hospital Bern
Collaborators
University of Bern, Hospital Centre Biel/Bienne

4. Oversight

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
Data Monitoring Committee
Yes

5. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Bladder Cancer, Non-muscle Invasive

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
33 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Epirubicin
Arm Type
Experimental
Arm Description
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.
Arm Title
Mitomycin
Arm Type
Experimental
Arm Description
Patients in that PDOs show highest response to this drug in-vitro will be treated with Mitomycin.
Arm Title
Gemcitabine
Arm Type
Experimental
Arm Description
Patients in that PDOs show highest response to this drug in-vitro will be treated with Gemcitabine.
Arm Title
Docetaxel
Arm Type
Experimental
Arm Description
Patients in that PDOs show highest response to this drug in-vitro will be treated with Docetaxel.
Intervention Type
Drug
Intervention Name(s)
Epirubicin
Intervention Description
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
Intervention Name(s)
Mitomycin
Intervention Description
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
Intervention Name(s)
Gemcitabine
Intervention Description
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
Intervention Name(s)
Docetaxel
Intervention Description
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.
Primary Outcome Measure Information:
Title
Number of patients with successful drug selection
Description
● 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.
Time Frame
24 months
Secondary Outcome Measure Information:
Title
Side effects
Description
Number of patients with side effects
Time Frame
24 months
Title
Recurrence rate
Description
Number of patients with recurrence
Time Frame
42 months
Title
QoL
Description
Quality of life will be determined using the SF-36 questionnaire
Time Frame
42 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Roland Seiler, MD
Phone
+4132 324 32 06
Email
urologie@szb-chb.ch
First Name & Middle Initial & Last Name or Official Title & Degree
Saskia Wehrli, MSc
Phone
+4132 324 32 06
Email
urologie@szb-chb.ch
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Roland Seiler, MD
Organizational Affiliation
Department of Urology
Official's Role
Study Chair
Facility Information:
Facility Name
Roland Seiler
City
Biel
ZIP/Postal Code
2501
Country
Switzerland
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Roland Seiler, Prof.
Phone
+41 32 324 24 24
Email
r_seiler@gmx.ch

12. IPD Sharing Statement

Plan to Share IPD
Yes

Learn more about this trial

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

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