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

M

Mansoura University

Status

Unknown

Conditions

Bladder Cancer

Treatments

Drug: Intravesical Bcg
Drug: Intravesical chemotherapy (epirubicin)

Study type

Interventional

Funder types

Other

Identifiers

NCT05146635
AE-12-2021

Details and patient eligibility

About

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.

Full 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.

Enrollment

110 estimated patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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

Trial design

Primary purpose

Treatment

Allocation

Randomized

Interventional model

Parallel Assignment

Masking

Single Blind

110 participants in 2 patient groups

Intravesical immunotherapy (BCG) group
Active Comparator group
Treatment:
Drug: Intravesical Bcg
Intravesical chemotherapy (Epirubicin) group
Active Comparator group
Treatment:
Drug: Intravesical chemotherapy (epirubicin)

Trial contacts and locations

1

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Central trial contact

Mahmoud Laymon; Amr A Elsawy

Data sourced from clinicaltrials.gov

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