Precise Neoadjuvant Chemoresection of Low Grade NMIBC

NCT ID: NCT06227065

Last Updated: 2024-01-26

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 28 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-10-31
• Study Completion Date: 2029-10-31

Brief 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. 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.

Conditions

Bladder Cancer; Non-muscle Invasive Bladder Cancer; Low-risk

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Epirubicin

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

Group Type: EXPERIMENTAL

Epirubicin

Intervention Type: DRUG

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

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

Group Type: EXPERIMENTAL

Mitomycin

Intervention Type: DRUG

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

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

Group Type: EXPERIMENTAL

Gemcitabine

Intervention Type: DRUG

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

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

Group Type: EXPERIMENTAL

Docetaxel

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: 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

Intervention Type: 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.

Intervention Type: 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.

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Spitalzentrum Biel

UNKNOWN

Sponsor Role: collaborator

University of Bern

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Roland Seiler, Prof.

Role: STUDY_CHAIR

Spitalzentrum Biel, University of Bern

Locations

Roland Seiler

Biel, , Switzerland

Countries

Switzerland

Central Contacts

Roland Seiler, Prof.

Role: CONTACT

urologie@szb-chb.ch

+41 32 324 32 06

Facility Contacts

Roland Seiler, Prof.

Role: primary

r_seiler@gmx.ch

+41 32 324 24 06

Other Identifiers

SZB-URO-24-001

Identifier Type: -

Identifier Source: org_study_id