Chemoablation or bladder resection with adjuvant chemotherapy in recurrent non-muscle invasive bladder cancer

The primary objective of this study is to evaluate the efficacy of a dose-dense **chemoablation** with Mitomycin C (MMC) compared to the standard treatment involving transurethral resection of bladder tumor (TURBT) followed by adjuvant intravesical instillation therapy in patients with recurrent Ta low-grade (LG) non-muscle invasive bladder cancer. This assessment is clinically relevant as it aims to determine whether the chemoablation approach offers superior long-term outcomes, potentially reducing recurrence rates and improving patient management strategies.

Secondary objectives include the hypothesis that chemoablation with MMC will lead to a permanently low recurrence rate in patients achieving complete response, while those without complete response may benefit more from adjuvant Bacillus Calmette-Guérin (BCG) therapy. This approach could result in a more favorable long-term recurrence-free survival (RFS) compared to the current standard regimen. Additionally, it is hypothesized that the number of TURBT procedures may decrease over time in the chemoablation group due to fewer recurrences and the avoidance of TURBT in patients with complete response.

The clinical trial focuses on individuals diagnosed with **recurrent non-muscle invasive bladder cancer**. The study population includes both male and female participants, aged 18 years and older. Participants are required to have experienced tumor recurrence following a previous urothelial tumor of Ta low-grade, with tumors smaller than 2 cm in diameter. The trial does not involve a vulnerable population. The sponsor has not provided information regarding the total number of participants. Participants must have the ability to understand and comprehend the provided written and oral information. The trial does not specify any particular lifestyle considerations such as diet or physical activity. The selection criteria ensure that participants have negative urine cytology, although this is optional. The sponsor has not disclosed further details about the general health status of the participants.

The clinical trial is designed to evaluate the efficacy of **mitomycin** chemoablation compared to standard treatment with transurethral resection of bladder tumor (TURBT) and adjuvant intravesical instillation therapy in patients with recurrent non-muscle invasive bladder cancer. This is a randomized, double-blind, controlled trial with an estimated duration from September 2024 to December 2027. The trial will involve a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as tumor recurrence after a previous urothelial tumor of Ta low-grade, tumor size less than 2 cm, and age of 18 years or older. Participants will be randomly assigned to receive either the investigational treatment or the standard treatment.

Study visits will include regular follow-up assessments to monitor the primary endpoint of two-year recurrence-free survival (RFS) and secondary endpoints such as five-year RFS, progression-free survival, and overall survival. The follow-up visits will occur at specified intervals to assess the number of tumors at first recurrence, the number of TURBTs required, and any serious adverse events related to the treatment. The end-of-study visit will conclude the participant's involvement, summarizing the outcomes and any adverse events experienced during the trial.

Participant involvement is expected to last up to five years, with conditions for early termination including withdrawal of consent, significant adverse events, or non-compliance with the study protocol. The trial aims to provide valuable insights into the long-term effects of **mitomycin** chemoablation compared to standard treatment, potentially influencing future therapeutic strategies for recurrent non-muscle invasive bladder cancer.

The clinical trial involves the use of **Mitomycin medac**, a pharmaceutical product formulated as a **powder and solvent for intravesical solution**. The active substance in this medication is **mitomycin**, a chemical compound classified under the ATC code L01DC03. The product is administered via **intravesical use** as a solution for injection. The maximum daily dose is 40 mg, with a total maximum dose of 240 mg over a treatment period of up to 2 weeks. The product is manufactured by Medac Gesellschaft für klinische Spezialpräparate mbH (Wedel) and is not a paediatric formulation. Participant compliance with the dosing schedule will be monitored throughout the trial.

Additionally, the study utilizes **BCG medac**, which is a **powder and solvent for intravesical suspension**. The active substance is **BCG (Bacillus Calmette-Guérin) bacteria**, a structurally diverse substance classified under the ATC code L03AX03. This product is also administered via **intravesical use** as a suspension for injection. The maximum daily dose is 50 ml, with a total maximum dose of 350 ml over a treatment period of up to 6 weeks. Like Mitomycin medac, BCG medac is produced by Medac Gesellschaft für klinische Spezialpräparate mbH (Wedel) and is not intended for paediatric use. The administration and dosing schedule will be closely monitored to ensure participant adherence.

Efficacy in the clinical trial titled "Chemoablation or bladder resection with adjuvant chemotherapy in recurrent non-muscle invasive bladder cancer" will be assessed using both primary and secondary endpoints. The primary endpoint is the two-year **recurrence-free survival (RFS)**, defined as the event of first recurrence following treatment, excluding the recurrence diagnosed at the time of inclusion or persisting tumor following chemoablation. Secondary endpoints include five-year RFS, the number of patients requiring transurethral resection of bladder tumor (TURBT) or tumor fulguration in the outpatient clinic within the first two years post-randomization, and the number of tumors at first recurrence categorized by intervals (1, 2-7, >8). Additional secondary endpoints are the number of TURBTs per patient over two and five years of follow-up, five-year progression-free survival, five-year overall survival, the number of patients completing the assigned intervention, and serious adverse events related to **mitomycin (MMC)** treatment during neoadjuvant or adjuvant therapy.