Precise Neoadjuvant Chemoresection of Low Grade NMIBC

Phase 2

Not yet recruiting

• Conditions: Bladder Cancer; Non-muscle Invasive Bladder Cancer; Low-risk
• Interventions: Drug: Epirubicin; Drug: Gemcitabine; Drug: Mitomycin; Drug: Docetaxel

• Registration Number: NCT06227065
• Lead Sponsor: University of Bern

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.

Study Timeline

• Status Verified: 2024-01
• Study First Submitted: 2024-01-17
• Study First Submitted QC: 2024-01-25
• Last Update Submitted: 2024-01-25
• Study First Posted: 2024-01-26
• Last Update Posted: 2024-01-26
• Study Start: 2024-10
• Primary Completion: 2026-10
• Study Completion: 2029-10

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 28

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

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

Primary Outcome Measures

Name	Time	Method
Pathological response	15 weeks	Rate of patients that show complete pathological response to neoadjuvant chemoresection

Secondary Outcome Measures

Name	Time	Method
Number of patients with recurrence free survival	1 Year	Recurrence after neoadjuvant chemoresection and transurethral resection of the bladder tumor
Tolerability of instillation	15 weeks	Composite endpoint determined by standardized questionnaires (EORTC QLQ-C30, QLQ-NMIBC24 and IPSS)
Feasibility of drug screen	4 weeks	Rate of patients in which drug screen in patient derived organoids was successful

Trial Locations

Locations (1)

Roland Seiler; 🇨🇭 Biel, Switzerland