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Præcis neoadjuverende kemoresektion af lavkvalitets NMIBC (POLO)

15. september 2026 opdateret af: Hospital Centre Biel/Bienne

Præcis neoadjuverende kemoresektion af lavgradig NMIBC styret af lægemiddelscreeninger i patientafledte organoider: Et enkelt center, åbent, fase II-forsøg

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.

Studieoversigt

Status

Ikke rekrutterer endnu

Betingelser

Intervention / Behandling

Detaljeret beskrivelse

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.

Undersøgelsestype

Interventionel

Tilmelding (Anslået)

28

Fase

  • Fase 2

Kontakter og lokationer

Dette afsnit indeholder kontaktoplysninger for dem, der udfører undersøgelsen, og oplysninger om, hvor denne undersøgelse udføres.

Studiekontakt

Undersøgelse Kontakt Backup

Studiesteder

  • Schweiz
      • Bern, Schweiz, 3001
        • Lindenhofspital, Klinik für Urologie
        • Kontakt:
        • Ledende efterforsker:
          • Bernard Kiss
      • Biel, Schweiz, 2501

Deltagelseskriterier

Forskere leder efter personer, der passer til en bestemt beskrivelse, kaldet berettigelseskriterier. Nogle eksempler på disse kriterier er en persons generelle helbredstilstand eller tidligere behandlinger.

Berettigelseskriterier

Aldre berettiget til at studere

18 år og ældre (Voksen, Ældre voksen)

Tager imod sunde frivillige

Ingen

Køn, der er berettiget til at studere

Alle

Beskrivelse

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.

Studieplan

Dette afsnit indeholder detaljer om studieplanen, herunder hvordan undersøgelsen er designet, og hvad undersøgelsen måler.

Hvordan er undersøgelsen tilrettelagt?

Design detaljer

  • Primært formål: Behandling
  • Tildeling: Ikke-randomiseret
  • Interventionel model: Enkelt gruppeopgave
  • Maskning: Ingen (Åben etiket)

Våben og indgreb

Deltagergruppe / Arm
Intervention / Behandling
Eksperimentel: Epirubicin

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

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

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

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

Hvad måler undersøgelsen?

Primære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Pathological response
Tidsramme: 15 weeks

Rate of patients that show complete pathological response to neoadjuvant chemoresection
15 weeks

Sekundære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Feasibility of drug screen
Tidsramme: 4 weeks

Rate of patients in which drug screen in patient derived organoids was successful
4 weeks
Safety of the study intervention
Tidsramme: 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
Number of patients with recurrence free survival
Tidsramme: 1 Year

Recurrence after neoadjuvant chemoresection and transurethral resection of the bladder tumor
1 Year
Tolerability of instillation
Tidsramme: 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
Tidsramme: 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

Samarbejdspartnere og efterforskere

Det er her, du vil finde personer og organisationer, der er involveret i denne undersøgelse.

Sponsor

Hospital Centre Biel/Bienne

Samarbejdspartnere

Lindenhofgruppe AG
Fond'action contre le cancer
Spitalzentrum Biel

Efterforskere

  • Studiestol: Roland Seiler, Prof., Spitalzentrum Biel

Datoer for undersøgelser

Disse datoer sporer fremskridtene for indsendelser af undersøgelsesrekord og resumeresultater til ClinicalTrials.gov. Studieregistreringer og rapporterede resultater gennemgås af National Library of Medicine (NLM) for at sikre, at de opfylder specifikke kvalitetskontrolstandarder, før de offentliggøres på den offentlige hjemmeside.

Studer store datoer

Studiestart (Anslået)

1. december 2026

Primær færdiggørelse (Anslået)

30. november 2030

Studieafslutning (Anslået)

30. november 2031

Datoer for studieregistrering

Først indsendt

17. januar 2024

Først indsendt, der opfyldte QC-kriterier

25. januar 2024

Først opslået (Faktiske)

26. januar 2024

Opdateringer af undersøgelsesjournaler

Sidste opdatering sendt (Faktiske)

18. september 2026

Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier

15. september 2026

Sidst verificeret

1. september 2026

Mere information

Begreber relateret til denne undersøgelse

Nøgleord

Yderligere relevante MeSH-vilkår

Andre undersøgelses-id-numre

  • SZB-URO-26-001

Plan for individuelle deltagerdata (IPD)

Planlægger du at dele individuelle deltagerdata (IPD)?

JA

IPD-planbeskrivelse

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

IPD-delingstidsramme

After completion of the trial to the primary endpoint.

IPD-deling Understøttende informationstype

  • STUDY_PROTOCOL

Lægemiddel- og udstyrsoplysninger, undersøgelsesdokumenter

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