Bladder CancerPhase 2POLONCT06227065
Precise Chemoresection in Low-grade NMIBC Using Drug Screens in Patient-derived Organoids
A Phase 2 study testing Epirubicin, Mitomycin and Gemcitabine in people with Bladder Cancer and Non-muscle Invasive Bladder Cancer, run by Hospital Centre Biel/Bienne at 2 sites in Switzerland.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Bladder Cancer, Non-muscle Invasive Bladder Cancer, Low Grade
- What is being tested?
- Epirubicin, Mitomycin and Gemcitabine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 28 participants
- Where
- 2 sitesSwitzerland
- Study dates
- 1 Dec 2026to 30 Nov 2031
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Signed Informed Consent Form
- Age ≥ 18 years
- Primary or recurrent NMIBC suspected to be low-grade or maximum G2 with a negative urine cytology
Who cannot join
- Anticoagulation other than acetylsalicylic acid
- Evidence of significant uncontrolled concomitant disease that could affect compliance with the protocol as judged by the investigator
- Severe infection within 4 weeks prior to the date of the patient's informed consent signature
- Contraindication for frequent catheterization
- 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
- 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
Show all 9Show fewer
- 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
- Vulnerable individual, e.g., individual incapable of judgement or currently incarcerated or oth-erwise institutionalized (prisoner), or refugee
- 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.
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
Switzerland2 sites
Lindenhofspital, Klinik für Urologie
Bern, 3001
Bernard Kiss, +41 31 300 38 88, bernhard.kiss@hin.ch
Bernard Kiss
Spitalzentrum Biel, Klinik für Urologie
Biel, 2501
Roland Seiler, Prof., +41 32 324 32 06, Roland.Seiler-Blarer@szb-chb.ch
Martina Schneider, +41 323243217, martina.schneider@szb-chb.ch
About this study
Official title: 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.
Read the 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.
- Being tested
- Epirubicin, Mitomycin, Gemcitabine, Docetaxel
- Keywords
- Patient derived organoids, Neoadjuvant chemoresection, Precise drug selection
- Medical subject headings
- Urinary Bladder Neoplasms, Non-Muscle Invasive Bladder Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EpirubicinDrug
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.
MitomycinDrug
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
GemcitabineDrug
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.
DocetaxelDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| Epirubicin | Experimental | Patients in that PDOs show highest response to this drug in-vitro will be treated with Epirubicin. Receives: Drug: Epirubicin |
| Mitomycin | Experimental | Patients in that PDOs show highest response to this drug in-vitro will be treated with Mitomycin. Receives: Drug: Mitomycin |
| Gemcitabine | Experimental | Patients in that PDOs show highest response to this drug in-vitro will be treated with Gemcitabine. Receives: Drug: Gemcitabine |
| Docetaxel | Experimental | Patients in that PDOs show highest response to this drug in-vitro will be treated with Docetaxel. Receives: Drug: Docetaxel |
What is being measured
The primary outcome is the main question the study is designed to answer.
Pathological response
Rate of patients that show complete pathological response to neoadjuvant chemoresection
Measured: 15 weeks
Secondary outcomes (5)
Feasibility of drug screen
Rate of patients in which drug screen in patient derived organoids was successful
Measured: 4 weeks
Safety of the study intervention
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
Measured: 12 weeks
Number of patients with recurrence free survival
Recurrence after neoadjuvant chemoresection and transurethral resection of the bladder tumor
Measured: 1 Year
Tolerability of instillation
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.
Measured: 24 weeks
Tolerability of instillation
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).
Measured: 24 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Jan 2024
- Study start1 Dec 2026 (estimated)
- Primary completion30 Nov 2030 (estimated)
- Study completion30 Nov 2031 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Bladder CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Model description
- Phase II, all 28 evaluable patients will follow the same treatment. Only, selection of the drug is performed using drug screens in patient derived organoids and is specific for each patient
- Masking
- None (open label)
- Enrolment
- 28 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Hospital Centre Biel/Bienne
- Sponsor type
- University, hospital or other
- Collaborators
- Spitalzentrum Biel, Lindenhofgruppe AG, Fond'action contre le cancer
- Responsible party
- Sponsor
- Investigators
- Roland Seiler, Prof., Study chair, Spitalzentrum Biel
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06227065
- Sponsor's protocol ID
- SZB-URO-26-001
- Acronym
- POLO
- Status last verified
- Sep 2026
- First submitted
- 17 Jan 2024
- Last updated
- 18 Sep 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: After completion of the trial for the primary endpoint, deidentified data will be shared to other researches upon request.
Study at a glance
From the registry record, last updated by the sponsor on 18 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- POLO-Trial. Precise Neoadjuvant Chemoresection of Low-grade NMIBC Guided by Drug Sceens in Patient-derived Or-ganoids. An Open-label, Phase II Trial.
- ClinicalTrials.gov ID
- NCT06227065
- Acronym / sponsor ID
- POLO / SZB-URO-26-001
- Keywords
- Patient derived organoids, Neoadjuvant chemoresection, Precise drug selection
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 28 participants (estimated)
- Lead sponsor
- Hospital Centre Biel/BienneUniversity, hospital or other
- Collaborators
- Spitalzentrum Biel, Lindenhofgruppe AG, Fond'action contre le cancer
- Study start
- 1 Dec 2026 (estimated)
- Primary completion
- 30 Nov 2030 (estimated)
- Study completion
- 30 Nov 2031 (estimated)
- First posted
- 26 Jan 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 4
- Model description
- Phase II, all 28 evaluable patients will follow the same treatment. Only, selection of the drug is performed using drug screens in patient derived organoids and is specific for each patient
| Arm | Type | Receives |
|---|---|---|
| Epirubicin | Experimental | Drug: EpirubicinPatients in that PDOs show highest response to this drug in-vitro will be treated with Epirubicin. |
| Mitomycin | Experimental | Drug: MitomycinPatients in that PDOs show highest response to this drug in-vitro will be treated with Mitomycin. |
| Gemcitabine | Experimental | Drug: GemcitabinePatients in that PDOs show highest response to this drug in-vitro will be treated with Gemcitabine. |
| Docetaxel | Experimental | Drug: DocetaxelPatients in that PDOs show highest response to this drug in-vitro will be treated with Docetaxel. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Signed Informed Consent Form
- Age ≥ 18 years
- Primary or recurrent NMIBC suspected to be low-grade or maximum G2 with a negative urine cytology
Key exclusion criteria (9 listed)
- Anticoagulation other than acetylsalicylic acid
- Evidence of significant uncontrolled concomitant disease that could affect compliance with the protocol as judged by the investigator
- Severe infection within 4 weeks prior to the date of the patient's informed consent signature
- Contraindication for frequent catheterization
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| EpirubicinIn 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. | Drug | Epirubicin |
| MitomycinIn 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 | Drug | Mitomycin |
| GemcitabineIn 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. | Drug | Gemcitabine |
| DocetaxelIn 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. | Drug | Docetaxel |
Primary outcome
Pathological response
Time frame: 15 weeks
Rate of patients that show complete pathological response to neoadjuvant chemoresection
5 secondary outcomes
Feasibility of drug screen
Time frame: 4 weeks
Safety of the study intervention
Time frame: 12 weeks
Number of patients with recurrence free survival
Time frame: 1 Year
Tolerability of instillation
Time frame: 24 weeks
Tolerability of instillation
Time frame: 24 weeks
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Sep 2026.
- Individual participant dataSharing planned: Yes. After completion of the trial for the primary endpoint, deidentified data will be shared to other researches upon request.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Roland Seiler, Prof. study chair
Spitalzentrum Biel
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Epirubicin, Mitomycin and Gemcitabine in people with Bladder Cancer and Non-muscle Invasive Bladder Cancer, run by Hospital Centre Biel/Bienne at 2 sites in Switzerland.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 18 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Switzerland. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Roland Seiler, Prof. (+41 32 324 32 06, urologie@szb-chb.ch), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Pathological response (time frame: 15 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Sep 2026.