NCT07061964

Combining Immunotherapy and Radiation Therapy to Help Patients Avoid Bladder Removal After Treatment Shrinks Muscle Invasive Bladder Cancer, BRIGHT Trial

Single Arm Phase II Study of Bladder Preservation With Immunoradiotherapy After a Clinically Meaningful Response to Neoadjuvant Therapy in Patients With Muscle Invasive Bladder Cancer (BRIGHT)

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 111 (estimated)
• Sponsor: National Cancer Institute (NCI) · NIH
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This phase II trial tests the effect of giving pembrolizumab in combination with radiation therapy after chemotherapy in preventing surgery to remove the bladder in patients with muscle invasive bladder cancer. Standard of care therapy includes chemotherapy before surgery (neoadjuvant) to shrink or get rid of the tumor. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the tumor, and may interfere with the ability of tumor cells to grow and spread. Radiation therapy uses high energy x-rays, particles, or radioactive seeds to kill cancer cells and shrink tumors. Photon beam radiation therapy is a type of radiation therapy that uses x-rays or gamma rays that come from a special machine called a linear accelerator. The radiation dose is delivered at the surface of the body and goes into the tumor and through the body. Giving pembrolizumab in combination with radiation therapy after neoadjuvant chemotherapy may help prevent surgical removal of the bladder in patients with muscle invasive bladder cancer.

Detailed description

PRIMARY OBJECTIVE: I. To evaluate whether 3-year bladder intact event-free survival (BI-EFS) is at least 70% in participants with clinically T0-clinically T1 without multifocal carcinoma in situ (CIS) following neoadjuvant therapy (NAT) for muscle-invasive bladder cancer (MIBC) who receive radiotherapy (RT) + pembrolizumab (MK-3475). SECONDARY OBJECTIVES: I. To estimate BI-EFS in participants who receive RT + pembrolizumab (MK-3475). II. To estimate local muscle invasive recurrence-free survival in participants who receive RT+ pembrolizumab (MK-3475). III. To estimate the metastasis-free survival (MFS) in participants who receive RT+ pembrolizumab (MK-3475). IV. To estimate the overall survival (OS) in participants who receive RT + pembrolizumab (MK-3475). V. To estimate the rate of salvage cystectomy in participants who receive RT+ pembrolizumab (MK-3475). VI. To evaluate the frequency and severity of toxicities in participants who receive RT + pembrolizumab (MK-3475). PATIENT REPORTED OUTCOMES (PRO)-COMMON TERMINOLOGY CRITERIA FOR ADVERSE EVENTS (CTCAE) OBJECTIVE: I. To evaluate participant-reported symptoms using selected items from Gastrointestinal, Genitourinary and sexual function domains of the PRO-CTCAE, with the goal of characterizing the frequency, severity, and interference of treatment-related symptoms. BANKING OBJECTIVE: I. To bank specimens for future correlative studies. OUTLINE: Patients undergo photon beam RT once daily (QD) on Monday-Friday for up to 20 treatments and receive pembrolizumab intravenously (IV) over 30 minutes on day 1 of each cycle. Cycles repeat every 21 days for up to 18 cycles (for a total of 12 months, including NAT) in the absence of disease progression or unacceptable toxicity. Patients also undergo transurethral resection of bladder tumor (TURBT) with tissue sample collection at pre-registration and computed tomography (CT), magnetic resonance imaging (MRI) or positron emission tomography (PET), cystoscopy, and urine and blood sample collection throughout the study. After completion of study treatment, patients are followed every 26 weeks until year 2 and then every 52 weeks up to year 5.

Conditions

• Muscle Invasive Bladder Urothelial Carcinoma
• Stage II Bladder Cancer AJCC v8
• Stage IIIA Bladder Cancer AJCC v8

Interventions

Type	Name	Description
PROCEDURE	Biospecimen Collection	Undergo tissue, urine, and blood sample collection
PROCEDURE	Computed Tomography	Undergo CT
PROCEDURE	Cystoscopy	Undergo cystoscopy
PROCEDURE	Magnetic Resonance Imaging	Undergo MRI
BIOLOGICAL	Pembrolizumab	Given IV
RADIATION	Photon Beam Radiation Therapy	Undergo photon beam RT
PROCEDURE	Positron Emission Tomography	Undergo PET
OTHER	Questionnaire Administration	Ancillary studies
PROCEDURE	Transurethral Resection of Bladder Tumor	Undergo TURBT

Timeline

• Start date: 2025-11-25
• Primary completion: 2027-07-31
• Completion: 2027-07-31
• First posted: 2025-07-14
• Last updated: 2026-04-13

Locations

131 sites across 1 country: United States

Regulatory

• FDA-regulated drug study