Precise Chemoresection in Low-grade NMIBC Using Drug Screens in Patient-derived Organoids (POLO)

September 15, 2026 updated by: Hospital Centre Biel/Bienne

POLO-Trial. Precise Neoadjuvant Chemoresection of Low-grade NMIBC Guided by Drug Sceens in Patient-derived Or-ganoids. An Open-label, Phase II Trial.

Based on the unmet clinical need to reduce invasiveness of treatment of low grade NMIBC, the investigators conduct this prospective, open label, single arm and single center phase II trial. The investigators aim to use drug screens in PDOs to guide neoadjuvant intravesical instillation therapy with either Epirubicin, Mitomycin C, Gemcitabine or Docetaxel to achieve chemoresection NMIBC.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed Description

Bladder cancer is a disease of the elderly patient and related to several interventions and operations. Patients with a low risk non-muscle invasive bladder cancer (NMIBC) are treated by transurethral resection of the bladder tumor (TURBT). Due to the high recurrence rate of approximately 50% within 2 years of diagnosis, patients are followed in outpatient clinic by cystoscopy for at least 5 years.

Beside recurrence of low grade NMIBC to low grade disease, progression to higher grade or stage is infrequent to rare. Therefore, expectant management and actives surveillance seems to be an option for selected patients that are unfit for surgery. Moreover, intravesical chemoresection has been attempted in order to avoid surgery. However, all patients were treated with the same chemotherapeutic agent and anticipated response rates were missed.

At least four different drugs have been used in daily routine and/or clinical trials for instillation therapies in NMIBC. Namely, Epirubicin, Mitomycin C, Gemcitabine and Docetaxel have been investigated and administered.

The molecular landscape of NMIBC is heterogeneous. Not only the mutational pattern but also the transcriptomic characteristics vary between different NMIBC. Although different agents are used on a routine daily bases and in clinical trials, they have not been administered based on the molecular landscape or biological likelihood of response.

The investigators recently developed a pipeline for the generation of patient derived organoids (PDO) in NMIBC. In brief: The bladder cancer is sampled during TURBT. Generation of organoids has been carefully optimized in order to yield high viability from each sample. Beside confirmation of similarities of the molecular landscape between parental NMIBC and subsequent PDO (in approx. 30 samples), the investigators established a standardized protocol to perform drug screens on these PDOs.

In this trial (POLO Trial) the investigators aim to generate PDOs from bladder cancer biopsies that are harvested in the outpatient clinic. Subsequent drug screen in PDOs for Epirubicin, Mitomycin C, Gemcitabine and Docetaxel will identify the most effective agent in this given patient. Prior TURBT, patient will receive 6 intravesical instillations with the identified agent as neoadjuvant treatment in order to perform chemoresection of the tumor. Three months after initial diagnosis, TURBT will be performed as the standard treatment and to confirm response rate of precise chemoresection.

Study Type

Interventional

Enrollment (Estimated)

28

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Signed Informed Consent Form
  2. Age ≥ 18 years
  3. Primary or recurrent NMIBC suspected to be low-grade or maximum G2 with a negative urine cytology

Exclusion Criteria:

  1. Anticoagulation other than acetylsalicylic acid
  2. Evidence of significant uncontrolled concomitant disease that could affect compliance with the protocol as judged by the investigator
  3. Severe infection within 4 weeks prior to the date of the patient's informed consent signature
  4. Contraindication for frequent catheterization
  5. Pregnancy or nursing. Female subject of childbearing potential (defined as premenopausal women who have not undergone surgical sterilization and are sexually active with a male part-ner) must have a negative urine pregnancy test at screening
  6. Female subject of childbearing potential who is unwilling to use effective contraception method(s) from the start of the intravesical instillation with the IMP until six months after the last instillation
  7. Male subject who is unwilling to use an effective contraception method from the start of the intravesical instillation with the IMP until four months after the last instillation
  8. Vulnerable individual, e.g., individual incapable of judgement or currently incarcerated or oth-erwise institutionalized (prisoner), or refugee
  9. Concomitant participation in another interventional clinical trial with an active treatment within 4 weeks prior to the date of the patient's informed consent signature and during the current trial.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

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

In PDOs from patients that show highest response to Epirubicin, this drug will be instilled intravesically once weekly for 6 times.

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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Pathological response
Time Frame: 15 weeks
Rate of patients that show complete pathological response to neoadjuvant chemoresection
15 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of patients with recurrence free survival
Time Frame: 1 Year
Recurrence after neoadjuvant chemoresection and transurethral resection of the bladder tumor
1 Year
Feasibility of drug screen
Time Frame: 4 weeks
Rate of patients in which drug screen in patient derived organoids was successful
4 weeks
Safety of the study intervention
Time Frame: 12 weeks
Incidence, severity and type of Adverse Events of Special Interest (AESIs) which are defined as adverse events related to chemotherapeutic intravesical instillation. AESIs include dysuria, urinary tract infections, and complications due to catheterism for intravesical instillation such as urethral irritation and haematuria
12 weeks
Tolerability of instillation
Time Frame: 24 weeks
Quality of life measured with the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30). It corresponds to a functional Scales & Global Health Status; a higher score indicates a better outcome (a higher level of functioning or a better quality of life). The score minimum is 0 and maximum 100.
24 weeks
Tolerability of instillation
Time Frame: 24 weeks

The quality of life is completed with a Symptom & Concern Scale specific for NMIBC called European Organisation for Research and Treatment of Cancer 24-Item Non-Muscle-Invasive Bladder Cancer Module (EORTC QLQ-NMIBC24).

This Symptom & Concern Scale has also a minimum score of 0 and a maximum of 100. A higher score indicates a worse outcome (a greater burden of symptoms or high symptomatology).
24 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Hospital Centre Biel/Bienne

Collaborators

Lindenhofgruppe AG
Fond'action contre le cancer
Spitalzentrum Biel

Investigators

  • Study Chair: Roland Seiler, Prof., Spitalzentrum Biel

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

December 1, 2026

Primary Completion (Estimated)

November 30, 2030

Study Completion (Estimated)

November 30, 2031

Study Registration Dates

First Submitted

January 17, 2024

First Submitted That Met QC Criteria

January 25, 2024

First Posted (Actual)

January 26, 2024

Study Record Updates

Last Update Posted (Actual)

September 18, 2026

Last Update Submitted That Met QC Criteria

September 15, 2026

Last Verified

September 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • SZB-URO-26-001

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

After completion of the trial for the primary endpoint, deidentified data will be shared to other researches upon request.

IPD Sharing Time Frame

After completion of the trial to the primary endpoint.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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