Clinical trial NCT06227065: Precise Neoadjuvant Chemoresection of Low Grade NMIBC
Official title: Precise Neoadjuvant Chemoresection of Low Grade NMIBC Guided by Drug Screens in Patient Derived Organoidst: A Single Center, Open-label, Phase II Trial
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: Bladder Cancer
Non-muscle Invasive Bladder Cancer
Low-risk
Keywords: Patient derived organoids
Neoadjuvant chemoresection
Precise drug selection
Lead sponsor: University of Bern
Sponsor class: OTHER
Collaborators: name: Spitalzentrum Biel
First posted: 2024-01-26
Enrollment: 28
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Intervention model description: 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
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Pathological response
timeFrame: 15 weeks
Secondary outcomes:
measure: Number of patients with recurrence free survival
timeFrame: 1 Year
measure: Tolerability of instillation
timeFrame: 15 weeks
measure: Feasibility of drug screen
timeFrame: 4 weeks
Other outcomes:
Locations:
city: Biel
country: Switzerland
facility: Roland Seiler
Study officials:
affiliation: Spitalzentrum Biel, University of Bern
name: Roland Seiler, Prof.
role: STUDY_CHAIR
References: