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NCT07061964PHASE2Recruiting

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

National Cancer Institute (NCI)

Start Date

11/25/2025

Completion Date

7/31/2027

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.

Eligibility Criteria

Age Range: 18 years to No maximum

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. 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) * 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 28 days prior to registration * Participants 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 participants 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

Interventions

PROCEDURE

Biospecimen Collection

PROCEDURE

Computed Tomography

PROCEDURE

Cystoscopy

PROCEDURE

Magnetic Resonance Imaging

BIOLOGICAL

Pembrolizumab

RADIATION

Photon Beam Radiation Therapy

PROCEDURE

Positron Emission Tomography

OTHER

Questionnaire Administration

PROCEDURE

Transurethral Resection of Bladder Tumor

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Conditions

Muscle Invasive Bladder Urothelial CarcinomaStage II Bladder Cancer AJCC v8Stage IIIA Bladder Cancer AJCC v8

Locations

University of Alabama at Birmingham Cancer Center

Birmingham, Alabama 35233

United States

Banner MD Anderson Cancer Center

Gilbert, Arizona 85234

United States

Mayo Clinic Hospital in Arizona

Phoenix, Arizona 85054

United States

Highlands Oncology Group - Fayetteville

Fayetteville, Arkansas 72703

United States

Highlands Oncology Group - Rogers

Rogers, Arkansas 72758

United States

Highlands Oncology Group

Springdale, Arkansas 72762

United States

Tower Cancer Research Foundation

Beverly Hills, California 90211

United States

City of Hope Corona

Corona, California 92882

United States

City of Hope Comprehensive Cancer Center

Duarte, California 91010

United States

City of Hope at Irvine Lennar

Irvine, California 92618

United States

City of Hope Antelope Valley

Lancaster, California 93534

United States

Los Angeles General Medical Center

Los Angeles, California 90033

United States

USC / Norris Comprehensive Cancer Center

Los Angeles, California 90033

United States

Cedars-Sinai Medical Center

Los Angeles, California 90048

United States

University of California Davis Comprehensive Cancer Center

Sacramento, California 95817

United States

City of Hope South Pasadena

South Pasadena, California 91030

United States

Cedars-Sinai Cancer - Tarzana

Tarzana, California 91356

United States

City of Hope Upland

Upland, California 91786

United States

UCHealth University of Colorado Hospital

Aurora, Colorado 80045

United States

UCHealth - Cherry Creek

Denver, Colorado 80206

United States

Shaw Cancer Center

Edwards, Colorado 81632

United States

Poudre Valley Hospital

Fort Collins, Colorado 80524

United States

Cancer Care and Hematology-Fort Collins

Fort Collins, Colorado 80528

United States

UCHealth Greeley Hospital

Greeley, Colorado 80631

United States

UCHealth Highlands Ranch Hospital

Highlands Ranch, Colorado 80129

United States

UCHealth Lone Tree Health Center

Lone Tree, Colorado 80124

United States

Medical Center of the Rockies

Loveland, Colorado 80538

United States

Mayo Clinic in Florida

Jacksonville, Florida 32224-9980

United States

Moffitt Cancer Center at SouthShore

Ruskin, Florida 33570

United States

Moffitt Cancer Center-International Plaza

Tampa, Florida 33607

United States

Moffitt Cancer Center - McKinley Campus

Tampa, Florida 33612

United States

Moffitt Cancer Center

Tampa, Florida 33612

United States

Moffitt Cancer Center at Wesley Chapel

Wesley Chapel, Florida 33544

United States

CTCA at Southeastern Regional Medical Center

Newnan, Georgia 30265

United States

Kootenai Health - Coeur d'Alene

Coeur d'Alene, Idaho 83814

United States

Kootenai Clinic Cancer Services - Post Falls

Post Falls, Idaho 83854

United States

Kootenai Clinic Cancer Services - Sandpoint

Sandpoint, Idaho 83864

United States

Rush-Copley Medical Center

Aurora, Illinois 60504

United States

OSF Saint Joseph Medical Center

Bloomington, Illinois 61701

United States

Illinois CancerCare-Bloomington

Bloomington, Illinois 61704

United States

Illinois CancerCare-Canton

Canton, Illinois 61520

United States

Illinois CancerCare-Carthage

Carthage, Illinois 62321

United States

Northwestern University

Chicago, Illinois 60611

United States

Carle at The Riverfront

Danville, Illinois 61832

United States

Cancer Care Specialists of Illinois - Decatur

Decatur, Illinois 62526

United States

Decatur Memorial Hospital

Decatur, Illinois 62526

United States

Northwestern Medicine Cancer Center Kishwaukee

DeKalb, Illinois 60115

United States

Illinois CancerCare-Dixon

Dixon, Illinois 61021

United States

Carle Physician Group-Effingham

Effingham, Illinois 62401

United States

Crossroads Cancer Center

Effingham, Illinois 62401

United States

Illinois CancerCare-Eureka

Eureka, Illinois 61530

United States

NorthShore University HealthSystem-Evanston Hospital

Evanston, Illinois 60201

United States

Illinois CancerCare-Galesburg

Galesburg, Illinois 61401

United States

Northwestern Medicine Cancer Center Delnor

Geneva, Illinois 60134

United States

NorthShore University HealthSystem-Glenbrook Hospital

Glenview, Illinois 60026

United States

Northwestern Medicine Glenview Outpatient Center

Glenview, Illinois 60026

United States

Northwestern Medicine Grayslake Outpatient Center

Grayslake, Illinois 60030

United States

NorthShore University HealthSystem-Highland Park Hospital

Highland Park, Illinois 60035

United States

Illinois CancerCare-Kewanee Clinic

Kewanee, Illinois 61443

United States

Northwestern Medicine Lake Forest Hospital

Lake Forest, Illinois 60045

United States

Illinois CancerCare-Macomb

Macomb, Illinois 61455

United States

Carle Physician Group-Mattoon/Charleston

Mattoon, Illinois 61938

United States

Cancer Care Center of O'Fallon

O'Fallon, Illinois 62269

United States

HSHS Saint Elizabeth's Hospital

O'Fallon, Illinois 62269

United States

Northwestern Medicine Oak Brook

Oak Brook, Illinois 60523

United States

Northwestern Medicine Orland Park

Orland Park, Illinois 60462

United States

Illinois CancerCare-Ottawa Clinic

Ottawa, Illinois 61350

United States

Illinois CancerCare-Pekin

Pekin, Illinois 61554

United States

Illinois CancerCare-Peoria

Peoria, Illinois 61615

United States

OSF Saint Francis Radiation Oncology at Peoria Cancer Center

Peoria, Illinois 61615

United States

OSF Saint Francis Medical Center

Peoria, Illinois 61637

United States

Illinois CancerCare-Peru

Peru, Illinois 61354

United States

Illinois CancerCare-Princeton

Princeton, Illinois 61356

United States

Southern Illinois University School of Medicine

Springfield, Illinois 62702

United States

Springfield Clinic

Springfield, Illinois 62702

United States

Springfield Memorial Hospital

Springfield, Illinois 62781

United States

Carle Cancer Center

Urbana, Illinois 61801

United States

Northwestern Medicine Cancer Center Warrenville

Warrenville, Illinois 60555

United States

Illinois CancerCare - Washington

Washington, Illinois 61571

United States

Mary Greeley Medical Center

Ames, Iowa 50010

United States

McFarland Clinic - Ames

Ames, Iowa 50010

United States

UI Health Care Mission Cancer and Blood - Ankeny Clinic

Ankeny, Iowa 50023

United States

McFarland Clinic - Boone

Boone, Iowa 50036

United States

Mercy Cancer Center-West Lakes

Clive, Iowa 50325

United States

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

Clive, Iowa 50325

United States

Iowa Methodist Medical Center

Des Moines, Iowa 50309

United States

UI Health Care Mission Cancer and Blood - Des Moines Clinic

Des Moines, Iowa 50309

United States

Mercy Medical Center - Des Moines

Des Moines, Iowa 50314

United States

UI Health Care Mission Cancer and Blood - Laurel Clinic

Des Moines, Iowa 50314

United States

McFarland Clinic - Trinity Cancer Center

Fort Dodge, Iowa 50501

United States

McFarland Clinic - Jefferson

Jefferson, Iowa 50129

United States

McFarland Clinic - Marshalltown

Marshalltown, Iowa 50158

United States

UI Health Care Mission Cancer and Blood - Waukee Clinic

Waukee, Iowa 50263

United States

The Iowa Clinic PC

West Des Moines, Iowa 50266

United States

University of Kentucky/Markey Cancer Center

Lexington, Kentucky 40536

United States

The James Graham Brown Cancer Center at University of Louisville

Louisville, Kentucky 40202

United States

UofL Health Medical Center Northeast

Louisville, Kentucky 40245

United States

University Medical Center New Orleans

New Orleans, Louisiana 70112

United States

Ochsner Medical Center Jefferson

New Orleans, Louisiana 70121

United States

Tufts Medical Center

Boston, Massachusetts 02111

United States

Dana-Farber Cancer Institute

Boston, Massachusetts 02215

United States

UMass Memorial Medical Center - University Campus

Worcester, Massachusetts 01655

United States

Sanford Joe Lueken Cancer Center

Bemidji, Minnesota 56601

United States

Fairview Southdale Hospital

Edina, Minnesota 55435

United States

Park Nicollet Clinic - Saint Louis Park

Saint Louis Park, Minnesota 55416

United States

University of Mississippi Medical Center

Jackson, Mississippi 39216

United States

Saint Francis Medical Center

Cape Girardeau, Missouri 63703

United States

Billings Clinic Cancer Center

Billings, Montana 59101

United States

Community Medical Center

Missoula, Montana 59804

United States

Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center

Lebanon, New Hampshire 03756

United States

Jefferson Cherry Hill Hospital

Cherry Hill, New Jersey 08002

United States

Hunterdon Medical Center

Flemington, New Jersey 08822

United States

Jersey City Medical Center

Jersey City, New Jersey 07302

United States

Cooperman Barnabas Medical Center

Livingston, New Jersey 07039

United States

Rutgers Cancer Institute of New Jersey

New Brunswick, New Jersey 08903

United States

Sidney Kimmel Cancer Center Washington Township

Sewell, New Jersey 08080

United States

The New York Hospital Medical Center of Queens

Flushing, New York 11355

United States

NYP/Weill Cornell Medical Center

New York, New York 10065

United States

Stony Brook University Medical Center

Stony Brook, New York 11794

United States

Sanford Broadway Medical Center

Fargo, North Dakota 58122

United States

Sanford Roger Maris Cancer Center

Fargo, North Dakota 58122

United States

University of Cincinnati Cancer Center-UC Medical Center

Cincinnati, Ohio 45219

United States

MetroHealth Medical Center

Cleveland, Ohio 44109

United States

University of Cincinnati Cancer Center-West Chester

West Chester, Ohio 45069

United States

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma 73104

United States

University of Pennsylvania/Abramson Cancer Center

Philadelphia, Pennsylvania 19104

United States

Thomas Jefferson University Hospital

Philadelphia, Pennsylvania 19107

United States

Asplundh Cancer Pavilion

Willow Grove, Pennsylvania 19090

United States

Sanford Cancer Center Oncology Clinic

Sioux Falls, South Dakota 57104

United States

Sanford USD Medical Center - Sioux Falls

Sioux Falls, South Dakota 57117-5134

United States

The West Clinic - Wolf River

Germantown, Tennessee 38138

United States

Parkland Memorial Hospital

Dallas, Texas 75235

United States

UT Southwestern Simmons Cancer Center - RedBird

Dallas, Texas 75237

United States

UT Southwestern/Simmons Cancer Center-Dallas

Dallas, Texas 75390

United States

UT Southwestern/Simmons Cancer Center-Fort Worth

Fort Worth, Texas 76104

United States

Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center

Houston, Texas 77030

United States

UT Southwestern Clinical Center at Richardson/Plano

Richardson, Texas 75080

United States

University of Texas Health Science Center at San Antonio

San Antonio, Texas 78229

United States

Scott and White Memorial Hospital

Temple, Texas 76508

United States

Huntsman Cancer Institute/University of Utah

Salt Lake City, Utah 84112

United States

Dartmouth Cancer Center - North

Saint Johnsbury, Vermont 05819

United States

VCU Massey Cancer Center at Stony Point

Richmond, Virginia 23235

United States

VCU Massey Comprehensive Cancer Center

Richmond, Virginia 23298

United States

Swedish Medical Center-First Hill

Seattle, Washington 98122

United States

West Virginia University Healthcare

Morgantown, West Virginia 26506

United States

Camden Clark Medical Center

Parkersburg, West Virginia 26101

United States

Ascension Northeast Wisconsin-Saint Elizabeth Cancer Center-Appleton

Appleton, Wisconsin 54915

United States

Ascension Southeast Wisconsin Hospital-Elmbrook Campus-Brookfield

Brookfield, Wisconsin 53045

United States

Ascension Calumet Hospital-Chilton

Chilton, Wisconsin 53014

United States

Reiman Cancer Center-Ascension Wisconsin Health Center-Rawson

Franklin, Wisconsin 53132

United States

Saint Vincent Hospital Cancer Center Green Bay

Green Bay, Wisconsin 54301

United States

Saint Vincent Hospital Cancer Center at Saint Mary's

Green Bay, Wisconsin 54303

United States

Ascension Columbia Saint Mary's Hospital-Ozaukee Campus-Mequon

Mequon, Wisconsin 53097

United States

Ascension Columbia Saint Mary's Hospital-Milwaukee Campus

Milwaukee, Wisconsin 53211

United States

Saint Vincent Hospital Cancer Center at Oconto Falls

Oconto Falls, Wisconsin 54154

United States

Ascension Northeast Wisconsin-Mercy Hospital-Oshkosh

Oshkosh, Wisconsin 54904

United States

Ascension All Saints Hospital-Spring Street-Racine

Racine, Wisconsin 53405

United States

Saint Vincent Hospital Cancer Center at Sheboygan

Sheboygan, Wisconsin 53081

United States

Saint Vincent Hospital Cancer Center at Sturgeon Bay

Sturgeon Bay, Wisconsin 54235-1495

United States

Ascension Southeast Wisconsin Hospital-Mayfair Road-Wauwatosa

Wauwatosa, Wisconsin 53226

United States