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

Recruiting now · Phase 2

Conditions studied: Muscle Invasive Bladder Urothelial Carcinoma, Stage II Bladder Cancer AJCC v8, Stage IIIA Bladder Cancer AJCC v8

In brief

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.

Key facts

Study ID

NCT07061964

Run by

National Cancer Institute (NCI)

People needed

111

Starts

2025-11-25

Expected to finish

2027-07-31

Last updated by the study team

2026-07-30

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Participants must have histologic evidence of cT2-T4aN0M0 muscle invasive urothelial carcinoma of the bladder within 180 days prior to starting neoadjuvant therapy (NAT)
• Participants must have had CT chest/abdomen/pelvis (C/A/P), MRI C/A/P or PET within 60 days prior to starting NAT to determine cT2-T4aN0M0
• Participants must have undergone TURBT with biopsy of areas of prior disease and systematic biopsies (left and right lateral, dome, posterior wall and trigone) and radiologic staging showing clinically T0-T1 disease within 60 days after the last dose of NAT. At least 4 out of 5 systematic biopsies must be performed
• NOTE: This TURBT must be within 90 days prior to registration. Registration must be within 90 days after the last dose of NAT
• Participants must have imaging of the chest, abdomen, and pelvis performed using CT or MRI preferably with contrast. Fludeoxyglucose F-18 (FDG) PET-CT can also be used for staging. If FDG PET-CT is used, then it is at the discretion of the investigator if they want to additionally obtain diagnostic CT or MRI with contrast within 60 days after the last dose of NAT
• Participants with lymph nodes ≥ 1.0 cm in the shortest cross-sectional diameter on imaging (CT or MRI of abdomen and pelvis) after completion of NAT must have a PET-CT within 70 days prior to registration. A biopsy in the setting of negative PET-CT is not required unless there is strong clinical suspicion for nodal involvement with tumor. Participants with a positive PET are deemed ineligible unless a biopsy is performed and shows no evidence of tumor involvement
• NOTE: For questions regarding the above eligibility criteria, please contact the study chairs in addition to the Southwest Oncology Group (SWOG) Statistics and Data Management Center (SDMC)
• Participants must not have evidence of ≥ T2, or N1-3, or M1 disease after NAT
• Participants must not have the presence of small cell, neuroendocrine carcinoma, plasmacytoid variants on any pathology
• Participants must not have had urothelial carcinoma or histological variant at any site outside of the urinary bladder within 24 months prior to registration except Ta/T1/carcinoma in situ (CIS) of the upper urinary tract, including renal pelvis or ureter if the participant underwent complete nephroureterectomy
• NOTE: Participants with mixed variant histology will be eligible for the trial if the majority (> 50%) of the tumor is urothelial cell carcinoma
• Participants will be allowed to continue PD-1/L-1 inhibitor therapy received as part of standard of care neoadjuvant therapy while they undergo pre-registration assessments (TURBT and imaging)
• Participants must have received at least 3 and no more than 6 cycles of Food and Drug Administration (FDA) approved NAT for MIBC. These include cisplatin-based combination chemotherapy (e.g. cisplatin and gemcitabine [GC] with or without PD-1/L1 inhibitors) dose dense or accelerated methotrexate, vinblastine, doxorubicin and cisplatin (MVAC) or enfortumab vedotin with PD-1/L1 inhibitor
• Participants must not have had anti-PD-1, anti PD-L1, anti PD-L2 or anti-CTLA4 antibody, any other antibody or drug targeting T-cell co-stimulation, enfortumab vedotin, or any other drug targeting nectin-4 other than for neoadjuvant treatment for MIBC
• NOTE: Prior intravesical immunotherapy or chemotherapy for non-muscle invasive disease is allowed
• Participants must not have had prior pelvic radiotherapy
• Participants must not have received a live attenuated vaccination within 28 days prior to registration
• Participants with conditions requiring immunosuppressive doses of steroids (> 10 mg/day of prednisone or equivalent) or other immunosuppressive medications must not be taking steroids at time of trial registration
• Participants must be ≥ 18 years old at the time of registration
• Participants must have Zubrod performance status of 0-2
• Participants must have a complete medical history and physical exam within 28 days prior to registration
• Leukocytes ≥ 3 x 10\^3/uL (within 28 days prior to registration)
• Absolute neutrophil count ≥ 1.5 x 10\^3/uL (within 28 days prior to registration)
• Platelets ≥ 100 x 10\^3/uL (within 28 days prior to registration)
• Total bilirubin ≤ institutional upper limit of normal (ULN) unless history of Gilbert's disease (within 28 days prior to registration)

Where it is running

• Banner MD Anderson Cancer Center — Gilbert, Arizona, United States (enrolling)
• Mayo Clinic Hospital in Arizona — Phoenix, Arizona, United States (enrolling)
• Highlands Oncology Group - Fayetteville — Fayetteville, Arkansas, United States (enrolling)
• Highlands Oncology Group - Rogers — Rogers, Arkansas, United States (enrolling)
• Highlands Oncology Group — Springdale, Arkansas, United States (enrolling)
• Tower Cancer Research Foundation — Beverly Hills, California, United States (enrolling)
• City of Hope Corona — Corona, California, United States (enrolling)
• City of Hope Comprehensive Cancer Center — Duarte, California, United States (enrolling)
• City of Hope at Irvine Lennar — Irvine, California, United States (enrolling)
• City of Hope Antelope Valley — Lancaster, California, United States (enrolling)
• Los Angeles General Medical Center — Los Angeles, California, United States (enrolling)
• USC / Norris Comprehensive Cancer Center — Los Angeles, California, United States (enrolling)
• Cedars-Sinai Medical Center — Los Angeles, California, United States (enrolling)
• University of California Davis Comprehensive Cancer Center — Sacramento, California, United States (enrolling)
• City of Hope South Pasadena — South Pasadena, California, United States (enrolling)
• Cedars-Sinai Cancer - Tarzana — Tarzana, California, United States (enrolling)
• City of Hope Upland — Upland, California, United States (enrolling)
• UCHealth University of Colorado Hospital — Aurora, Colorado, United States (enrolling)
• UCHealth - Cherry Creek — Denver, Colorado, United States (enrolling)
• Shaw Cancer Center — Edwards, Colorado, United States (enrolling)
• Poudre Valley Hospital — Fort Collins, Colorado, United States (enrolling)
• Cancer Care and Hematology-Fort Collins — Fort Collins, Colorado, United States (enrolling)
• UCHealth Greeley Hospital — Greeley, Colorado, United States (enrolling)
• UCHealth Highlands Ranch Hospital — Highlands Ranch, Colorado, United States (enrolling)
• University of Alabama at Birmingham Cancer Center — Birmingham, Alabama, United States (enrolling)

Full record on ClinicalTrials.gov

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