Precise Neoadjuvant Chemoresection of Low Grade NMIBC

NCT06227065 | Not Yet Recruiting Phase 2 DMC

• 1 other identifier: SZB-URO-24-001
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 1

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.

Conditions

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

Keywords

Patient derived organoids; Neoadjuvant chemoresection; Precise drug selection

Outcome Measures

Primary Outcomes (1)

• Pathological response

  Rate of patients that show complete pathological response to neoadjuvant chemoresection

  15 weeks

Secondary Outcomes (3)

• Number of patients with recurrence free survival

  1 Year

• Tolerability of instillation

  15 weeks

• Feasibility of drug screen

  4 weeks

Study Arms (4)

Epirubicin

EXPERIMENTAL

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

Drug: Epirubicin

Mitomycin

EXPERIMENTAL

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

Drug: Mitomycin

Gemcitabine

EXPERIMENTAL

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

Drug: Gemcitabine

Docetaxel

EXPERIMENTAL

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

Drug: Docetaxel

Interventions

Epirubicin 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.

Epirubicin

Mitomycin 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

Mitomycin

Gemcitabine 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.

Gemcitabine

Docetaxel 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.

Docetaxel

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Bern: lead
• Spitalzentrum Biel: collaborator

Study Sites (1)

Roland Seiler

Biel, 2501, Switzerland

Location

MeSH Terms

Conditions

Urinary Bladder Neoplasms; Non-Muscle Invasive Bladder Neoplasms

Interventions

Epirubicin; Mitomycin; Gemcitabine; Docetaxel

Condition Hierarchy (Ancestors)

Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Intervention Hierarchy (Ancestors)

Doxorubicin; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Mitomycins; Indolequinones; Quinones; Azirines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Diterpenes; Terpenes

Study Officials

• Roland Seiler, Prof.

  Spitalzentrum Biel, University of Bern

  STUDY CHAIR

Central Study Contacts

Roland Seiler, Prof.

CONTACT

+41 32 324 32 06; urologie@szb-chb.ch

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Phase II, all 28 patients will follow the same treatment. Only, selection of the use drug is performed using drug screens in patient derived organoids and is specific for each patient

Study Record Dates

• First Submitted: January 17, 2024
• First Posted: January 26, 2024
• Study Start: October 1, 2024
• Primary Completion (Estimated): October 1, 2026
• Study Completion (Estimated): October 1, 2029
• Last Updated: January 26, 2024

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: After completion of the trial to the primary endpoint.

Locations

CH (1)