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NCT07061964 | RECRUITING | Muscle Invasive Bladder Urothelial Carcinoma

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

National Cancer Institute (NCI)

Brief 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.

Condition or disease

Muscle Invasive Bladder Urothelial Carcinoma

Stage II Bladder Cancer AJCC v8

Stage IIIA Bladder Cancer AJCC v8

Intervention/treatment

Biospecimen Collection

Computed Tomography

Cystoscopy

Magnetic Resonance Imaging

Pembrolizumab

Photon Beam Radiation Therapy

Positron Emission Tomography

Questionnaire Administration

Transurethral Resection of Bladder Tumor

Phase

PHASE2

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 (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.

Study Type : INTERVENTIONAL
Estimated Enrollment : 111 participants
Masking : NONE
Primary Purpose : TREATMENT
Official Title : 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)
Actual Study Start Date : 2026-06-01
Estimated Primary Completion Date : 2027-07-31
Estimated Study Completion Date : 2027-07-31

Information not available for Arms and Intervention/treatment

Ages Eligible for Study: 18 Years
Sexes Eligible for Study: ALL
Accepts Healthy Volunteers:
Criteria
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
Combining Immunotherapy and Radiation Therapy to Help Patients Avoid Bladder Removal After Treatment Shrinks Muscle Invasive Bladder Cancer, BRIGHT Trial

Location Details

NCT07061964

Please Choose a site

How to Participate

Want to participate in this study, select a site at your convenience, send yourself email to get contact details and prescreening steps.

Locations

RECRUITING

United States, alabama

University of Alabama at Birmingham Cancer Center

Birmingham, alabama, United States, 35233

SUSPENDED

United States, California

Cedars Sinai Medical Center

Los Angeles, California, United States, 90048

SUSPENDED

United States, Colorado

Shaw Cancer Center

Edwards, Colorado, United States, 81632

SUSPENDED

United States, Idaho

Kootenai Health - Coeur d'Alene

Coeur d'Alene, Idaho, United States, 83814

SUSPENDED

United States, Idaho

Kootenai Clinic Cancer Services - Post Falls

Post Falls, Idaho, United States, 83854

SUSPENDED

United States, Idaho

Kootenai Clinic Cancer Services - Sandpoint

Sandpoint, Idaho, United States, 83864

SUSPENDED

United States, Illinois

Illinois CancerCare-Bloomington

Bloomington, Illinois, United States, 61704

SUSPENDED

United States, Illinois

Illinois CancerCare-Canton

Canton, Illinois, United States, 61520

SUSPENDED

United States, Illinois

Illinois CancerCare-Carthage

Carthage, Illinois, United States, 62321

RECRUITING

United States, Illinois

Northwestern University

Chicago, Illinois, United States, 60611

RECRUITING

United States, Illinois

Cancer Care Specialists of Illinois - Decatur

Decatur, Illinois, United States, 62526

RECRUITING

United States, Illinois

Decatur Memorial Hospital

Decatur, Illinois, United States, 62526

SUSPENDED

United States, Illinois

Illinois CancerCare-Dixon

Dixon, Illinois, United States, 61021

SUSPENDED

United States, Illinois

Crossroads Cancer Center

Effingham, Illinois, United States, 62401

SUSPENDED

United States, Illinois

Illinois CancerCare-Eureka

Eureka, Illinois, United States, 61530

SUSPENDED

United States, Illinois

Illinois CancerCare-Galesburg

Galesburg, Illinois, United States, 61401

SUSPENDED

United States, Illinois

Illinois CancerCare-Kewanee Clinic

Kewanee, Illinois, United States, 61443

SUSPENDED

United States, Illinois

Illinois CancerCare-Macomb

Macomb, Illinois, United States, 61455

SUSPENDED

United States, Illinois

Illinois CancerCare-Ottawa Clinic

Ottawa, Illinois, United States, 61350

SUSPENDED

United States, Illinois

Illinois CancerCare-Pekin

Pekin, Illinois, United States, 61554

SUSPENDED

United States, Illinois

Illinois CancerCare-Peoria

Peoria, Illinois, United States, 61615

SUSPENDED

United States, Illinois

Illinois CancerCare-Peru

Peru, Illinois, United States, 61354

SUSPENDED

United States, Illinois

Illinois CancerCare-Princeton

Princeton, Illinois, United States, 61356

RECRUITING

United States, Illinois

Southern Illinois University School of Medicine

Springfield, Illinois, United States, 62702

SUSPENDED

United States, Illinois

Illinois CancerCare - Washington

Washington, Illinois, United States, 61571

SUSPENDED

United States, Iowa

Mary Greeley Medical Center

Ames, Iowa, United States, 50010

SUSPENDED

United States, Iowa

McFarland Clinic - Ames

Ames, Iowa, United States, 50010

SUSPENDED

United States, Iowa

McFarland Clinic - Boone

Boone, Iowa, United States, 50036

RECRUITING

United States, Iowa

Mercy Cancer Center-West Lakes

Clive, Iowa, United States, 50325

RECRUITING

United States, Iowa

Mercy Medical Center - Des Moines

Des Moines, Iowa, United States, 50314

SUSPENDED

United States, Iowa

McFarland Clinic - Trinity Cancer Center

Fort Dodge, Iowa, United States, 50501

SUSPENDED

United States, Iowa

McFarland Clinic - Jefferson

Jefferson, Iowa, United States, 50129

SUSPENDED

United States, Iowa

McFarland Clinic - Marshalltown

Marshalltown, Iowa, United States, 50158

RECRUITING

United States, Missouri

Saint Francis Medical Center

Cape Girardeau, Missouri, United States, 63703

SUSPENDED

United States, Montana

Community Medical Center

Missoula, Montana, United States, 59804