Precise Neoadjuvant Chemoresection of Low Grade NMIBC

Studien-Informationen Einschlusskriterien Studien-Rationale Studien-Arme Geprüfte Regime

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NCT-Nummer:
NCT06227065

Studienbeginn:
Oktober 2024

Letztes Update:
26.01.2024

Wirkstoff:
Epirubicin, Mitomycin, Gemcitabine, Docetaxel

Indikation (Clinical Trials):
Urinary Bladder Neoplasms, Non-Muscle Invasive Bladder Neoplasms

Geschlecht:
Alle

Altersgruppe:
Erwachsene (18+)

Phase:
Phase 2

Sponsor:
University of Bern

Collaborator:
Spitalzentrum Biel

Studienleiter

Roland Seiler, Prof.
Study Chair
Spitalzentrum Biel, University of Bern

Kontakt

Roland Seiler, Prof.
Kontakt:
Phone: +41 32 324 32 06
E-Mail: urologie@szb-chb.ch» Kontaktdaten anzeigen

Studienlocations
(1 von 1)

Roland Seiler
2501 Biel
Switzerland» Google-Maps
Ansprechpartner:
Roland Seiler, Prof.
Phone: +41 32 324 24 06
E-Mail: r_seiler@gmx.ch» Ansprechpartner anzeigen

Studien-Informationen

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.

Ein-/Ausschlusskriterien

Inclusion Criteria:

- Age ≥ 18 years

- Signed Informed Consent Form

- ECOG performance status of 0 or 1

- Previous history of low risk non-muscle invasive urothelial carcino-ma of the bladder

with recurrent papillary tumor and negative urine cytology or Primary solitary

papillary tumor, <3cm and negative urine cytology

Exclusion Criteria:

- Known previous high grade and/or intermediate or high risk non-muscle invasive bladder

cancer

- Anticoagulation other than acetylsalicylic acid

- Previous Intravesical biological/immuno- (BCG) therapy

- Evidence of significant uncontrolled concomitant disease that could affect compliance

with the protocol

Studien-Rationale

Primary outcome:

1. Pathological response (Time Frame - 15 weeks):
Rate of patients that show complete pathological response to neoadjuvant chemoresection

Secondary outcome:

1. Number of patients with recurrence free survival (Time Frame - 1 Year):
Recurrence after neoadjuvant chemoresection and transurethral resection of the bladder tumor

2. Tolerability of instillation (Time Frame - 15 weeks):
Composite endpoint determined by standardized questionnaires (EORTC QLQ-C30, QLQ-NMIBC24 and IPSS)

3. Feasibility of drug screen (Time Frame - 4 weeks):
Rate of patients in which drug screen in patient derived organoids was successful

Studien-Arme

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

Geprüfte Regime

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.
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
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.
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.

Quelle: ClinicalTrials.gov

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