Evaluation of Intravesical Neoadjuvant Chemotherapy with Cisplatin for Recurrence Prevention in Non-Muscle Invasive Bladder Cancer

The primary objective of this randomized clinical trial is the **evaluation** of the rate of early recurrences of non-muscle invasive bladder cancer (NMIBC) by comparing the efficacy of intravesical instillation of neoadjuvant chemotherapy prior to transurethral resection of bladder tumor (TURBT) against conventional TURBT without neoadjuvant chemotherapy. This is clinically relevant as it aims to determine the potential benefit of neoadjuvant chemotherapy in reducing early recurrence rates, which is a significant concern in the management of NMIBC.

Secondary objectives include:

• Evaluation of **toxicity**, adverse events, and complications attributable to intravesical instillation of chemotherapy prior to TURBT.
• Determination of the rate of late recurrences (between 12 and 60 months after the intervention) in both groups.
• Comparison of the recurrence-free time between the two groups.
• Identification of clinical and demographic variables that could influence a better clinical response.
• Assessment of differences in recurrence rates, adverse effects, and other variables between patients in the intervention group who have received different drugs.

The clinical trial focuses on individuals diagnosed with **non-muscle invasive bladder cancer**. The study population includes both male and female participants aged 18 years and older. Participants are required to have clinical and/or imaging evidence of the condition with an indication for transurethral resection of bladder tumor (TURBT). The trial excludes vulnerable populations and requires participants to have a Karnofsky scale score greater than 70%, indicating a relatively good general health status. Participants must have a history of stage Ta/T1, G1-G3 bladder cancer without concomitant carcinoma in situ, and a disease-free period of at least six months. Tumors must be less than 3 cm in size. The sponsor has not provided information regarding the total number of participants or specific lifestyle considerations such as diet or physical activity. The selection criteria ensure that the study population is well-defined and appropriate for evaluating the trial's main objective.

The clinical trial is designed as a **randomized**, open-label study to evaluate the efficacy of bladder instillation of neoadjuvant **chemotherapy** in conjunction with transurethral resection of bladder tumors (TURBT) for the prevention of recurrence in patients with non-muscle invasive bladder cancer. The trial aims to compare the early recurrence rates of non-muscle invasive bladder cancer (CVNMI) between patients receiving intravesical instillation of neoadjuvant chemotherapy and those undergoing conventional TURBT without neoadjuvant chemotherapy. The study is expected to run from May 18, 2018, to May 1, 2029, with the primary endpoint being the early recurrence rate of CVNMI. Secondary endpoints include the assessment of adverse events related to the drugs administered, as well as demographic and clinical characteristics of the participants.

Participants will be involved in the study for a maximum treatment period of one day, with the possibility of early termination if adverse events occur or if the participant withdraws consent. The study will include an initial screening visit to confirm eligibility based on criteria such as age, clinical evidence of CVNMI, and a Karnofsky scale score greater than 70%. Following the screening, eligible participants will undergo the assigned treatment procedure. Follow-up visits will be scheduled to monitor the participants' health status and to collect data on the primary and secondary endpoints. The end-of-study visit will conclude the participant's involvement, during which final assessments will be conducted to evaluate the treatment's efficacy and safety.

Inclusion criteria for the study require participants to be at least 18 years old, with clinical or imaging evidence of CVNMI and an indication for TURBT. Participants must have a history of stage Ta/T1, G1-G3 CVNMI without concomitant carcinoma in situ, and a disease-free period of at least six months. Tumors must be less than 3 cm in size. Participants must also provide informed consent to participate in the study. The trial will utilize chemotherapeutic agents such as **cisplatin**, **doxorubicin hydrochloride**, **mitomycin**, **gemcitabine**, **docetaxel**, and **epirubicin hydrochloride**, all administered via intravesical use. The study is categorized as a low-intervention trial, with a focus on evaluating the safety and efficacy of the neoadjuvant chemotherapy approach in preventing cancer recurrence.

The clinical trial involves the administration of several **chemotherapeutic agents** for the treatment of nonmuscle-invasive urothelial carcinoma. The first experimental medication is **Cisplatin**, marketed as Cisplatino Pharmacia 1 mg/ml concentrado para solución para perfusión EFG. This medication is provided in the form of a solution for infusion and is administered via intravesical use. The maximum daily dose is 30 mg, with a total treatment period of one day. The product is manufactured by Pharmacia Nostrum S.A. and is classified under the ATC code L01XA01.

Another experimental treatment is **Doxorubicin Hydrochloride**, available as Farmiblastina 50 mg polvo para solución inyectable. This medication is also administered intravesically, with a maximum daily dose of 50 mg. The pharmaceutical form is a solution for injection, and the treatment period is limited to one day. Pfizer S.L. is the manufacturer, and the ATC classification is L01DB01.

**Mitomycin** is included in the trial as Mitomicina Accord 40 mg polvo para solución inyectable y para perfusión EFG. It is administered intravesically with a maximum daily dose of 40 mg. The pharmaceutical form is a solution for injection/infusion, and the treatment duration is one day. Accord Healthcare S.L.U. is responsible for its production, and it is classified under ATC code L01DC03.

**Gemcitabine** is provided as Gemcitabina Accord 1 g Pó para solução para perfusão. This solution for infusion is administered intravesically, with a maximum daily dose of 38 mg. The treatment period is one day, and the product is manufactured by Accord Healthcare S.L.U. The ATC classification is L01BC05.

**Docetaxel** is administered as Docetaxel Aurovitas 20 mg/ml concentrado para solución para perfusión. This solution for infusion is given intravesically, with a maximum daily dose of 40 mg. The treatment period is one day, and Eugia Pharma (Malta) Ltd is the manufacturer. The ATC code for this medication is L01CD02.

Lastly, **Epirubicin Hydrochloride** is included as Farmorubicina 50 mg polvo para solución inyectable y para perfusión. This solution for injection/infusion is administered intravesically, with a maximum daily dose of 50 mg. The treatment period is one day, and Pfizer, S.L. is the manufacturer. The ATC classification is L01DB03.

All medications are administered via intravesical use, and participant compliance is monitored throughout the trial. The trial aims to evaluate the efficacy of these neoadjuvant chemotherapeutic agents in preventing the recurrence of nonmuscle-invasive urothelial carcinoma.

The efficacy of the clinical trial will be assessed by evaluating the primary endpoint, which is the early recurrence rate of **nonmuscle-invasive urothelial carcinoma** (CVNMI). This will involve comparing the outcomes of patients receiving intravesical instillation of neoadjuvant chemotherapy in conjunction with transurethral resection of bladder tumor (TURBT) to those undergoing conventional TURBT without neoadjuvant chemotherapy. The assessment will focus on determining the effectiveness of the neoadjuvant chemotherapy in preventing early recurrences of CVNMI.

Secondary endpoints will include the evaluation of adverse events associated with the administered drugs, as well as the collection of demographic and clinical characteristics such as age, sex, TNM classification, risk group, time of evolution, and previous treatments received. These parameters will be collected and analyzed to provide a comprehensive understanding of the treatment's efficacy and safety profile. The trial is designed to ensure rigorous data collection and analysis, adhering to the highest standards of clinical research.