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

NCT ID: NCT07061964

Last Updated: 2025-11-12

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE2

Total Enrollment

111 participants

Study Classification

INTERVENTIONAL

Study Start Date

2026-06-01

Study Completion Date

2027-07-31

Brief Summary

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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

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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 (12 months) 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

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

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Treatment (photon beam RT, pembrolizumab)

Patients undergo photon beam RT QD on Monday-Friday for up to 20 treatments and receive pembrolizumab IV over 30 minutes on day 1 of each cycle. Cycles repeat every 21 days for up to 18 cycles (12 months) in the absence of disease progression or unacceptable toxicity. Patients also undergo TURBT with tissue sample collection at pre-registration and CT, MRI or PET, cystoscopy, and urine and blood sample collection throughout the study.

Group Type EXPERIMENTAL

Biospecimen Collection

Intervention Type PROCEDURE

Undergo tissue, urine, and blood sample collection

Computed Tomography

Intervention Type PROCEDURE

Undergo CT

Cystoscopy

Intervention Type PROCEDURE

Undergo cystoscopy

Magnetic Resonance Imaging

Intervention Type PROCEDURE

Undergo MRI

Pembrolizumab

Intervention Type BIOLOGICAL

Given IV

Photon Beam Radiation Therapy

Intervention Type RADIATION

Undergo photon beam RT

Positron Emission Tomography

Intervention Type PROCEDURE

Undergo PET

Questionnaire Administration

Intervention Type OTHER

Ancillary studies

Transurethral Resection of Bladder Tumor

Intervention Type PROCEDURE

Undergo TURBT

Interventions

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Biospecimen Collection

Undergo tissue, urine, and blood sample collection

Intervention Type PROCEDURE

Computed Tomography

Undergo CT

Intervention Type PROCEDURE

Cystoscopy

Undergo cystoscopy

Intervention Type PROCEDURE

Magnetic Resonance Imaging

Undergo MRI

Intervention Type PROCEDURE

Pembrolizumab

Given IV

Intervention Type BIOLOGICAL

Photon Beam Radiation Therapy

Undergo photon beam RT

Intervention Type RADIATION

Positron Emission Tomography

Undergo PET

Intervention Type PROCEDURE

Questionnaire Administration

Ancillary studies

Intervention Type OTHER

Transurethral Resection of Bladder Tumor

Undergo TURBT

Intervention Type PROCEDURE

Other Intervention Names

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Biological Sample Collection Biospecimen Collected Specimen Collection CAT CAT Scan Computed Axial Tomography Computerized Axial Tomography Computerized axial tomography (procedure) Computerized Tomography Computerized Tomography (CT) scan CT CT Scan Diagnostic CAT Scan Diagnostic CAT Scan Service Type tomography CS Magnetic Resonance Magnetic Resonance Imaging (MRI) Magnetic resonance imaging (procedure) Magnetic Resonance Imaging Scan Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance MR MR Imaging MRI MRI Scan MRIs NMR Imaging NMRI Nuclear Magnetic Resonance Imaging sMRI Structural MRI BCD-201 GME 751 GME751 Keytruda Lambrolizumab MK 3475 MK-3475 MK3475 Pembrolizumab Biosimilar BCD-201 Pembrolizumab Biosimilar GME751 Pembrolizumab Biosimilar QL2107 Pembrolizumab Biosimilar RPH-075 Pembrolizumab Biosimilar SB27 QL2107 RPH 075 RPH-075 RPH075 SB 27 SB-27 SB27 SCH 900475 SCH-900475 SCH900475 External beam radiation therapy using photons (procedure) Photon Photon EBRT Photon External Beam Radiotherapy PHOTON Therapy Radiation, Photon Beam Medical Imaging, Positron Emission Tomography PET PET Scan Positron emission tomography (procedure) Positron Emission Tomography Scan Positron-Emission Tomography PT Transurethral resection (TURBT) TURBT

Eligibility Criteria

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Inclusion Criteria

* 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

* 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, N1-3 or metastatic 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 must have received at least 3 and no more than 6 cycles of National Comprehensive Cancer Network (NCCN) guideline concordant NAT 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 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
* 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)

* Participants with history of Gilbert's disease must have total bilirubin ≤ 5 x institutional ULN
* Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ≤ 3 x institutional ULN (within 28 days prior to registration)
* Participants must have a creatinine ≤ the institutional (I)ULN OR measured OR calculated creatinine clearance ≥ 40 mL/min using the following Cockcroft-Gault Formula. This specimen must have been drawn and processed within 3 days prior to registration
* Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class II or better
* Participants with a history of human immunodeficiency virus (HIV)-infection must be on effective anti-retroviral therapy at registration and have undetectable viral load test on the most recent test results obtained within 6 months prior to registration
* For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
* Participants with a history of hepatitis C virus (HCV) infection must have been treated and cured (defined as undetectable HCV viral load)
* Participants must not have a prior or concurrent malignancy whose natural history or treatment (in the opinion of the treating physician) has the potential to interfere with the safety or efficacy assessment of the investigational regimen
* Participants must not be pregnant or nursing (nursing includes breast milk fed to an infant by any means, including from the breast, milk expressed by hand, or pumped). Individuals who are of reproductive potential must have agreed to use an effective contraceptive method with details provided as a part of the consent process. A person who has had menses at any time in the preceding 12 consecutive months or who has semen likely to contain sperm is considered to be of "reproductive potential." In addition to routine contraceptive methods, "effective contraception" also includes refraining from sexual activity that might result in pregnancy and surgery intended to prevent pregnancy (or with a side-effect of pregnancy prevention) including hysterectomy, bilateral oophorectomy, bilateral tubal ligation/occlusion, and vasectomy with testing showing no sperm in the semen
* Participants must be offered the opportunity to participate in specimen banking
* Participants who can complete the PRO-CTCAE questionnaire in English or Spanish will be offered the opportunity to participate in the optional patient-reported outcome study
* NOTE: As a part of the Oncology Patient Enrollment Network (OPEN) registration process the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system

* Participants must be informed of the investigational nature of this study and must sign and give informed consent in accordance with institutional and federal guidelines
* For participants with impaired decision-making capabilities, legally authorized representatives may sign and give informed consent on behalf of study participants in accordance with applicable federal, local, and central institutional review board (CIRB) regulations
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Cancer Institute (NCI)

NIH

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Leslie Ballas

Role: PRINCIPAL_INVESTIGATOR

SWOG Cancer Research Network

Locations

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University of Alabama at Birmingham Cancer Center

Birmingham, Alabama, United States

Site Status RECRUITING

Tower Cancer Research Foundation

Beverly Hills, California, United States

Site Status RECRUITING

Cedars Sinai Medical Center

Los Angeles, California, United States

Site Status RECRUITING

Shaw Cancer Center

Edwards, Colorado, United States

Site Status SUSPENDED

Kootenai Health - Coeur d'Alene

Coeur d'Alene, Idaho, United States

Site Status SUSPENDED

Kootenai Clinic Cancer Services - Post Falls

Post Falls, Idaho, United States

Site Status SUSPENDED

Kootenai Clinic Cancer Services - Sandpoint

Sandpoint, Idaho, United States

Site Status SUSPENDED

OSF Saint Joseph Medical Center

Bloomington, Illinois, United States

Site Status RECRUITING

Illinois CancerCare-Bloomington

Bloomington, Illinois, United States

Site Status RECRUITING

Illinois CancerCare-Canton

Canton, Illinois, United States

Site Status RECRUITING

Illinois CancerCare-Carthage

Carthage, Illinois, United States

Site Status RECRUITING

Northwestern University

Chicago, Illinois, United States

Site Status RECRUITING

Cancer Care Specialists of Illinois - Decatur

Decatur, Illinois, United States

Site Status RECRUITING

Decatur Memorial Hospital

Decatur, Illinois, United States

Site Status RECRUITING

Illinois CancerCare-Dixon

Dixon, Illinois, United States

Site Status SUSPENDED

Crossroads Cancer Center

Effingham, Illinois, United States

Site Status SUSPENDED

Illinois CancerCare-Eureka

Eureka, Illinois, United States

Site Status RECRUITING

Illinois CancerCare-Galesburg

Galesburg, Illinois, United States

Site Status RECRUITING

Illinois CancerCare-Kewanee Clinic

Kewanee, Illinois, United States

Site Status RECRUITING

Illinois CancerCare-Macomb

Macomb, Illinois, United States

Site Status RECRUITING

Illinois CancerCare-Ottawa Clinic

Ottawa, Illinois, United States

Site Status RECRUITING

Illinois CancerCare-Pekin

Pekin, Illinois, United States

Site Status RECRUITING

Illinois CancerCare-Peoria

Peoria, Illinois, United States

Site Status RECRUITING

OSF Saint Francis Radiation Oncology at Peoria Cancer Center

Peoria, Illinois, United States

Site Status RECRUITING

OSF Saint Francis Medical Center

Peoria, Illinois, United States

Site Status RECRUITING

Illinois CancerCare-Peru

Peru, Illinois, United States

Site Status RECRUITING

Illinois CancerCare-Princeton

Princeton, Illinois, United States

Site Status RECRUITING

Southern Illinois University School of Medicine

Springfield, Illinois, United States

Site Status RECRUITING

Springfield Clinic

Springfield, Illinois, United States

Site Status RECRUITING

Springfield Memorial Hospital

Springfield, Illinois, United States

Site Status RECRUITING

Illinois CancerCare - Washington

Washington, Illinois, United States

Site Status RECRUITING

Mary Greeley Medical Center

Ames, Iowa, United States

Site Status RECRUITING

McFarland Clinic - Ames

Ames, Iowa, United States

Site Status RECRUITING

UI Health Care Mission Cancer and Blood - Ankeny Clinic

Ankeny, Iowa, United States

Site Status RECRUITING

McFarland Clinic - Boone

Boone, Iowa, United States

Site Status SUSPENDED

Mercy Cancer Center-West Lakes

Clive, Iowa, United States

Site Status RECRUITING

UI Health Care Mission Cancer and Blood - West Des Moines Clinic

Clive, Iowa, United States

Site Status RECRUITING

Iowa Methodist Medical Center

Des Moines, Iowa, United States

Site Status RECRUITING

UI Health Care Mission Cancer and Blood - Des Moines Clinic

Des Moines, Iowa, United States

Site Status RECRUITING

Mercy Medical Center - Des Moines

Des Moines, Iowa, United States

Site Status RECRUITING

UI Health Care Mission Cancer and Blood - Laurel Clinic

Des Moines, Iowa, United States

Site Status RECRUITING

McFarland Clinic - Trinity Cancer Center

Fort Dodge, Iowa, United States

Site Status SUSPENDED

McFarland Clinic - Jefferson

Jefferson, Iowa, United States

Site Status SUSPENDED

McFarland Clinic - Marshalltown

Marshalltown, Iowa, United States

Site Status SUSPENDED

UI Health Care Mission Cancer and Blood - Waukee Clinic

Waukee, Iowa, United States

Site Status RECRUITING

The Iowa Clinic PC

West Des Moines, Iowa, United States

Site Status RECRUITING

Saint Francis Medical Center

Cape Girardeau, Missouri, United States

Site Status RECRUITING

Community Medical Center

Missoula, Montana, United States

Site Status SUSPENDED

Thomas Jefferson University Hospital

Philadelphia, Pennsylvania, United States

Site Status RECRUITING

Countries

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United States

Facility Contacts

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Other Identifiers

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NCI-2025-04663

Identifier Type: REGISTRY

Identifier Source: secondary_id

S2427

Identifier Type: OTHER

Identifier Source: secondary_id

S2427

Identifier Type: OTHER

Identifier Source: secondary_id

U10CA180888

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NCI-2025-04663

Identifier Type: -

Identifier Source: org_study_id