Radiotherapy for BCG-unresponsive Non-muscle-invasive Carcinoma in Situ (CIS) Bladder Cancer

Radiotherapy for BCG-unresponsive Non-muscle-invasive Carcinoma in Situ (CIS) Bladder Cancer: an Open-label, Single-arm, Multicenter, Phase 2 Study

The investigators aim to investigate a possible role for radiotherapy in good prognosis bladder cancer patients has been identified as a possible alternative to cystectomy, especially for patients non-eligible for surgery but has yet to be fully explored.

Study Overview

• Status: Not yet recruiting
• Conditions: Bladder Cancer
• Intervention / Treatment: Radiation: radiation therapy

Detailed Description

Bladder cancer is the tenth most commonly diagnosed cancer with urothelial carcinoma representing 90% of all bladder cancer cases. Approximately three-quarters of patients diagnosed with urothelial carcinoma have non-muscle invasive disease (NMIBC) confined to the mucosa (stage Ta or carcinoma in situ (CIS)) or submucosa (stage T1). The gold standard for diagnosing CIS is a combination of cystoscopy, urine cytology, and histological evaluation. Diagnosis and resection of visible Ta/T1 tumors is done by transurethral resection of bladder tumors (TURBT). Standard treatment for patients with high-risk NMIBC (high-grade Ta, CIS, or any T1) following staging consists of intravesical Bacillus Calmette-Guerin (BCG) immunotherapy. BCG, even administered optimally, does not provide absolute protection. BCG failure is generally considered recurrence or progression during therapy. Clinical trial data comparing salvage therapies after BCG are quite heterogeneous, in part due to inconsistent definitions and reporting methods.

Patients who are BCG-unresponsive have a 20-40% risk for progression to muscle-invasive bladder cancer within 5 years, which carries a 50% risk for the development of incurable metastatic disease.

Interestingly, although chemoradiotherapy is a recognized standard of care in muscle-invasive bladder cancer (MIBC), it has not been adequately explored in NMIBC. However, the available data suggests that NMIBC is a radioresponsive malignancy and that in a proportion of patients bladder preservation would be possible.

The investigators aim to evaluate the use of radiotherapy in patients with high-grade non-muscle-invasive bladder cancer who have BCG failure, potentiating its effect with commonly use radiosensitizers.

• Study Type: Interventional
• Enrollment (Estimated): 50
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: EORTC; Phone Number: +3227741611; Email: eortc@eortc.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 18 years or older with histologically confirmed, BCG-unresponsive, high-risk non-muscle-invasive bladder cancer of predominantly (>50%) urothelial histology who were ineligible for or declined to undergo radical cystectomy
• Patients with carcinoma in situ with or without high-grade Ta or T1
• Eastern Cooperative Oncology Group performance status of 0-2, and adequate organ function
• Patients with concomitant Ta and T1 tumours must have undergone complete TURBT, defined as per standard of care as a visually complete resection (residual carcinoma in situ, which is traditionally not amenable to complete transurethral resection is acceptable), and the most recent cystoscopy or TURBT must have been done within 12 weeks before study initiation. Presence of detrusor muscle on pathology samples is required to ensure sample adequacy. A second TURBT is recommended but not required for patients with T1 tumours. The use of either white-light cystoscopy or blue-light cystoscopy is permitted, but the same technique has to be used in a patient throughout the trial
• Definition of BCG unresponsive non-muscle-invasive bladder cancer according to the European Association of Urology (EAU) guidelines

Exclusion Criteria:

• Evidence of upper urinary tract carcinoma
• Hydronephrosis due to tumour in the presence of T1 disease
• Patients on current systemic therapy for bladder cancer
• Patients who have received pelvic external beam radiotherapy within the previous 5 years

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Radiotherapy arm; Radiation therapy will be given covering the whole bladder over 4 weeks. The use of a radiosensitizing agent is mandatory.	Radiation: radiation therapy; Radiation therapy will be given in 20 fractions of 2.75 Gy covering the whole bladder over 4 weeks. The use of a radiosensitizing agent is mandatory. Each recruiting center will have to choose 2 options of radiosensitizing agents.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Proportion of patients with a complete response at 6 months post-radiotherapy	6 months post-radiotherapy

Secondary Outcome Measures

Outcome Measure	Time Frame
Progression-free survival	5 years from randomisation
overall survival	5 years from randomisation

Collaborators and Investigators

• Sponsor: European Organisation for Research and Treatment of Cancer - EORTC
• Investigators: Study Chair: Verane Achard, Dr, Fribourg Cantonal Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): March 1, 2025
• Primary Completion (Estimated): October 1, 2025
• Study Completion (Estimated): March 1, 2030

Study Registration Dates

• First Submitted: March 7, 2024
• First Submitted That Met QC Criteria: March 7, 2024
• First Posted (Actual): March 15, 2024

Study Record Updates

• Last Update Posted (Actual): July 22, 2024
• Last Update Submitted That Met QC Criteria: July 18, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Keywords: NMIBC
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Urologic Diseases; Carcinoma; Neoplasms, Glandular and Epithelial; Urinary Bladder Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Carcinoma in Situ; Urinary Bladder Neoplasms
• Other Study ID Numbers: EORTC 2335-GUCG

Drug and device information, study documents

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