Optimal Adjuvant Intravesical Therapy for Intermediate Risk Non Muscle Invasive Bladder Cancer: A Randomized Controlled Trial

The objective of this prospective, single-center randomized controlled trial is to identify the optimal adjuvant intravesical therapy in patients with intermediate risk (IR) non muscle invasive bladder cancer by comparing two commonly utilized intravesical regimens; intravesical immunotherapy (BCG) and intravesical chemotherapy.

Study Overview

• Status: Recruiting
• Conditions: Bladder Cancer
• Intervention / Treatment: Drug: Intravesical Bcg; Drug: Intravesical chemotherapy (epirubicin)

Detailed Description

Bladder cancer (BC) represents a frequent urologic malignancy, and is mainly diagnosed as non-muscle invasive, At presentation, approximately 30% of patients have muscle-invasive BC (clinical T2 or higher) .

Both the natural history of non-muscle-invasive bladder cancer (NMIBC) and its treatment strategies are highly variable. Although some patients never experience disease recurrence, others experience disease progression and eventually die of their disease .

In the absence of intravesical treatment, a patient with non-muscle-invasive BC has a 47% probability of disease recurrence within 5 years of diagnosis and a 9% probability of progression to muscle-invasive disease .

Low-, intermediate- and high-risk categories have been defined to help guide the treatment of patients with NMIBC (Ta, T1, and CIS). Treatment of NMIBC is now relatively well-defined for high-risk and low-risk disease presentation, and awaits further refinement through improvements in therapeutic options .

Solitary low-grade tumors, especially smaller lesions (3 cm or less), respond best to resection and immediate instillation of intravesical agents, whereas higher risk lesions, such as carcinoma in situ and high-grade T1 stage disease, have demonstrated good response to BCG when given on a schedule of induction (an initial 6-week course) and maintenance (3-weekly courses every 6 months for 3 years) .

However, while low- and high-risk diseases have been well-classified, the intermediate-risk (IR) category has traditionally comprised a heterogeneous group of patients that do not fit into either of these categories . As a result, many urologists remain uncertain about the categorization of patients as 'intermediate-risk' as well as the selection of the most appropriate therapeutic option for this patient population .

The pathology of IR NMIBC has been defined by different organizations (American Urological Association, European Association of Urology, National Comprehensive Cancer Network, and International Consultation on Urological Diseases) as those patients with recurrent (<1 year) low-grade Ta disease, solitary low-grade Ta >3cm, multifocal low-grade Ta disease or high-grade Ta disease <3 cm .

Current recommendations for therapy from the aforementioned organizations suggest a basic role for induction and maintenance therapy with either immunotherapy or chemotherapy. Data from a number of recent trials suggest that BCG with maintenance is superior to maintenance chemotherapy in this population as regard to recurrence free survival. On the other hand, no significant benefit of BCG compared with chemotherapy for tumor progression was identified.

Most of these studies were limited by its heterogeneity of patients (non-standardized definition of IR) and non-unified regimen of intravesical treatment (course or utilized chemotherapeutic agent). A well-designed randomized controlled trial with a rigorous methodology is warranted to provide a solid evidence for best practice in this special group of patients.

• Study Type: Interventional
• Enrollment (Anticipated): 110
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Egypt
  • DK
    • Mansoura, DK, Egypt, 35516
      • Recruiting
      • Mansoura Urology and Nephrology Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Adult patients (aged >18 years)
• Patients with primary or recurrent papillary NMIBC.
• Complete TURBT.
• Patients with IR NMIBC confirmed by histopathology.

Exclusion Criteria:

• Inability to give informed consent.
• Patients with history of previous radiotherapy or systemic chemotherapy.
• Patients suffering from immuno-deficiency or other malignancies.
• Patients with history of hypersensitivity reaction to BCG or epirubicin.
• Examination under anesthesia (EUA) reveals palpable bladder mass.
• Patients with low or high risk NMIBC by histopathology

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Intravesical immunotherapy (BCG) group	Drug: Intravesical Bcg; Patients will receive induction and maintenance BCG after complete TURBT.
Active Comparator: Intravesical chemotherapy (Epirubicin) group	Drug: Intravesical chemotherapy (epirubicin); Patients will receive induction and maintenance epirubicin after complete TURBT.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tumor recurrence rate	Number of patient who will develop Recurrence rate during follow up	2 years
Tumor Progression rate	Number of patient who will develop Progression rate during follow up	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Side effects from intravesical treatments	Side effects from intravesical treatments	2 years

Collaborators and Investigators

• Sponsor: Mansoura University

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2021
• Primary Completion (Anticipated): December 1, 2022
• Study Completion (Anticipated): January 1, 2023

Study Registration Dates

• First Submitted: November 23, 2021
• First Submitted That Met QC Criteria: November 23, 2021
• First Posted (Actual): December 7, 2021

Study Record Updates

• Last Update Posted (Actual): January 11, 2022
• Last Update Submitted That Met QC Criteria: December 21, 2021
• Last Verified: December 1, 2021

More Information

Terms related to this study

• Keywords: Progression; Bladder cancer; Recurrence; Intravesical therapy
• Additional Relevant MeSH Terms: Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Urologic Diseases; Urinary Bladder Diseases; Urinary Bladder Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Antibiotics, Antineoplastic; Epirubicin
• Other Study ID Numbers: AE-12-2021

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No