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

Bladder Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06310369
• Other study ID #: EORTC 2335-GUCG
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: March 1, 2025
• Est. completion date: March 1, 2030

Study information

• Verified date: March 2024
• Source: European Organisation for Research and Treatment of Cancer - EORTC
• Contact: EORTC
• Phone: +3227741611
• Email: eortc[@]eortc.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

We 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.

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. We 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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 50
• Est. completion date: March 1, 2030
• Est. primary completion date: October 1, 2025
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years to 100 Years

Eligibility

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 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

Related Conditions & MeSH terms

• Bladder Cancer
• Carcinoma in Situ
• Urinary Bladder Neoplasms

Intervention

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.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
European Organisation for Research and Treatment of Cancer - EORTC

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proportion of patients with a CR at 6 months post-radiotherapy		6 months post-radiotherapy
Secondary	Progression-free survival		5 years from randomisation
Secondary	overall survival		5 years from randomisation