Comparative Study of Adjuvant Gemcitabine Versus Mitomycin in Intermediate-Risk Non-Muscle Invasive Bladder Cancer

The primary objective of this study is to evaluate whether **adjuvant gemcitabine** improves recurrence-free survival compared to adjuvant **mitomycin** in patients with primary or recurrent non-muscle invasive bladder cancer (NMIBC) at intermediate risk of recurrence following transurethral tumor resection. This is clinically relevant as improving recurrence-free survival can significantly impact patient outcomes by potentially reducing the frequency of cancer recurrence and the need for further invasive treatments.

Secondary objectives include assessing local side effects and health-related quality of life (HRQoL) two weeks after the last instillation, progression-free survival, health economy, and adverse events. These secondary measures provide a comprehensive evaluation of the treatment's impact on patient well-being and healthcare resource utilization, which are critical for understanding the broader implications of the treatment options.

The clinical trial involves participants diagnosed with **primary or recurrent non-muscle invasive bladder cancer** with an intermediate risk of recurrence following transurethral tumor resection. The study population includes both male and female subjects, with an age range that encompasses adults and the elderly. The trial does not specify the total number of participants, as the sponsor has not provided this information. Participants were selected based on their diagnosis of non-muscle invasive bladder cancer, with a focus on those at intermediate risk of recurrence. The trial includes a vulnerable population, although specific lifestyle considerations such as diet, physical activity, or habits are not detailed. The study aims to evaluate the efficacy of adjuvant gemcitabine in improving recurrence-free survival compared to adjuvant mitomycin.

The clinical trial is designed to evaluate the efficacy of **gemcitabine** compared to **mitomycin** in improving recurrence-free survival in patients with primary or recurrent non-muscle invasive bladder cancer with an intermediate risk of recurrence following transurethral tumor resection. This study is a randomized, double-blind, controlled trial, ensuring that neither the participants nor the investigators are aware of the treatment assignments, thus minimizing bias. The trial is expected to span approximately five years, with an estimated end date of January 1, 2026.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to assess eligibility based on the principal inclusion criteria, which include having primary or recurrent non-muscle invasive bladder cancer with an intermediate risk of recurrence. Following successful screening, participants will be randomly assigned to receive either gemcitabine or mitomycin. The treatment period will last up to six months, during which participants will receive the investigational product via intravesical use. Follow-up visits will be scheduled to monitor the primary endpoint of recurrence-free survival and secondary endpoints such as local toxicity, health-related quality of life (HRQoL) two weeks after the last installation, progression-free survival, health economy, and adverse events.

The end-of-study visit will occur after the completion of the treatment period and follow-up assessments. The expected length of participant involvement is approximately six months, with conditions for early termination including the occurrence of significant adverse events or withdrawal of consent. The trial aims to provide robust data on the comparative effectiveness of these two chemotherapeutic agents in the specified patient population.

The clinical trial involves the use of two experimental medications: **Mitomycin** and **Gemcitabine**. **Mitomycin**, marketed as Mitomycin medac, is provided in a pharmaceutical form of powder and liquid for intravesical solution. The active substance, **Mitomycin**, is a chemical compound with the ATC code L01DC03. The medication is administered via intravesical use, with a maximum daily dose of 40 mg and a total maximum dose of 240 mg over a treatment period of six months. The product is manufactured by MEDAC GESELLSCHAFT FÜR KLINISCHE SPEZIALPRÄPARATE MBH (WEDEL) and is not a paediatric formulation. Participant compliance is monitored to ensure adherence to the dosing schedule.

**Gemcitabine**, marketed as Gemcitabine Accord, is provided as a concentrate for solution for infusion. The active substance, **Gemcitabine**, is also a chemical compound, identified by the ATC code L01BC05. This medication is administered via intravesical use, with a maximum daily dose of 1000 mg and a total maximum dose of 6000 mg over a six-month treatment period. The product is manufactured by ACCORD HEALTHCARE B.V. and is not formulated for paediatric use. Compliance with the dosing schedule is monitored throughout the trial to ensure accurate administration.

In this study, no non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatment are utilized. The trial aims to compare the efficacy of adjuvant **Gemcitabine** against adjuvant **Mitomycin** in improving recurrence-free survival in patients with intermediate-risk non-muscle invasive bladder cancer (NMIBC). The trial is designed to ensure rigorous monitoring of participant compliance and accurate administration of the investigational drugs.

The efficacy of the clinical trial titled "Adjuvant instillations in intermediate risk NMIBC: A Study comparIng Gemcitabine and MitomYciN (SIGYN-trial)" will be assessed primarily through the parameter of **recurrence-free survival**. This primary endpoint will evaluate the duration in which patients remain free from recurrence of non-muscle invasive bladder cancer (NMIBC) following treatment with either gemcitabine or mitomycin. Secondary endpoints include assessments of local toxicity and health-related quality of life (HRQol) two weeks after the last instillation, progression-free survival, health economy, and adverse events.

The trial aims to determine if adjuvant gemcitabine improves recurrence-free survival compared to adjuvant mitomycin. The collection and analysis of these efficacy parameters will be conducted at specified timepoints, although the exact schedule is not detailed in the provided data. The trial is expected to conclude by January 1, 2026, with recruitment having started on April 16, 2021. The study will involve the administration of gemcitabine and mitomycin, both delivered via intravesical use, with a maximum treatment period of six months for each participant.