Testing the Addition of the Immunotherapy Drug, Pembrolizumab, to Radiation Therapy Compared to the Usual Chemotherapy Treatment During Radiation Therapy for Bladder Cancer, PARRC Trial
Randomized Phase II Trial of Pembrolizumab and Radiation vs. Radiation and Concurrent Chemotherapy for High-Grade T1 Bladder Cancer (PARRC Trial)
3 other identifiers
interventional
160
2 countries
125
Brief Summary
This phase II trial compares the use of pembrolizumab and radiation therapy to chemotherapy with cisplatin, gemcitabine, 5-fluorouracil or mitomycin-C and radiation therapy for the treatment of non-muscle invasive bladder cancer. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Chemotherapy drugs, such as cisplatin, gemcitabine, 5-fluorouracil or mitomycin-C, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Radiation therapy uses high energy x-rays, particles, or radioactive seeds to kill cancer cells and shrink tumors. Giving pembrolizumab with radiation may kill more tumor cells than chemotherapy with radiation therapy in patients with non-muscle invasive bladder cancer.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2
Started Jun 2025
Longer than P75 for phase_2
125 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
January 9, 2025
CompletedFirst Posted
Study publicly available on registry
January 13, 2025
CompletedStudy Start
First participant enrolled
June 3, 2025
CompletedPrimary Completion
Last participant's last visit for primary outcome
February 1, 2032
ExpectedStudy Completion
Last participant's last visit for all outcomes
February 1, 2032
May 6, 2026
December 1, 2025
6.7 years
January 9, 2025
May 5, 2026
Conditions
Outcome Measures
Primary Outcomes (2)
Bladder intact event-free survival (BIEFS)
Defined as time free of histologically proven recurrent T1-T4 recurrence, clinical evidence of nodal or distant metastasis, radical cystectomy (either for disease progression or due to toxicity), or death from any cause. Analysis will consist of estimation of the BIEFS curves via the Kaplan-Meier estimator and testing of the primary hypothesis using the stratified logrank test (one-sided). Additionally, the Cox proportional hazards model will be used to estimate the hazard ratio adjusting for stratification variables and any other baseline covariates that demonstrate any degree of imbalance by treatment arm.
Up to 5 years
Global quality of life
Assessed using European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC-QLQ-C30) global quality of life domain.
Up to 5 years
Secondary Outcomes (8)
Complete response by cystoscopy
At 6 months
Disease free survival
Up to 5 years
Local-regional control
Up to 5 years
Metastasis free survival
Up to 5 years
Overall survival
Up to 5 years
- +3 more secondary outcomes
Other Outcomes (3)
Quality adjusted survival
Up to 2 years
Fatigue
Up to 2 years
Cumulative global quality of life
Up to 2 years
Study Arms (2)
Arm 1 (Chemotherapy and radiation)
ACTIVE COMPARATORPatients receive one of the following chemotherapy regimens per physicians choice: 1) cisplatin IV once per week for 4 weeks, 2) gemcitabine IV on days 1, 4, 8, 11, 15, 18, 22, and 25, or 3) mitomycin IV on day 1 and 5-fluorouracil IV continuously over 120 hours on days 1-5 and 16-20. Patients receiving cisplatin or gemcitabine continue chemotherapy for 6 weeks if they are receiving radiation according to the standard hypofractionated radiation schedule. Starting on day 1, patients also receive radiation therapy for 20, 32, or 36 treatments over 4-7 weeks. Treatment is given in the absence of disease progression or unacceptable toxicity. Patients also undergo CT/MRI and blood sample collection throughout the study. Patients may also undergo optional urine sample collection on study.
Arm 2 (Pembrolizumab and radiation)
EXPERIMENTALPatients receive pembrolizumab IV over 25-40 minutes on day 1 of each cycle. Cycles repeat every 6 weeks for 9 cycles in the absence of disease progression or unacceptable toxicity. Starting on day 1, patients also receive radiation therapy for 20, 32, or 36 treatments over 4-7 weeks. Treatment is given in the absence of disease progression or unacceptable toxicity. Patients also undergo CT/MRI and blood sample collection throughout the study. Patients may also undergo optional urine sample collection on study.
Interventions
Undergo CT
Given IV
Undergo MRI
Given IV
Given IV
Ancillary studies
Undergo radiation therapy
Given IV
Undergo blood and urine sample collection
Given IV
Eligibility Criteria
You may qualify if:
- Pathologically (histologically) proven diagnosis of T1 high-grade non-muscle invasive urothelial carcinoma of the bladder without radiographic evidence of regional nodal disease or metastatic disease (N0, M0) on CT, MRI, or positron emission tomography (PET)/CT scan who would otherwise be treated with cystectomy off-trial. Patients should have cystectomy recommended disease but do not need to be medically operable for a cystectomy to be eligible for the trial.
- NOTE: Patients with nodal disease ≥ 1 cm on short-axis or with suspicious nodes that are PET-avid of any size are not eligible
- High grade T1 disease history that must meet at least ONE of the three criteria below:
- Histologically confirmed recurrence with high-grade T1 urothelial carcinoma (+/- focal carcinoma in situ \[CIS\]) in the bladder following initial transurethral resection of bladder tumor (TURBT) and at least one induction course of intravesical therapy. Adequate induction course is defined as ≥ 5 doses of intravesical Bacillus Calmette-Guerin (BCG) or intravesical chemotherapy when BCG is not available.
- T1 with pathologic high-risk features (lymphovascular invasion \[LVI\] or variant histology of micropapillary, sarcomatoid, or plasmacytoid features) post initial TURBT. (No prior intravesical therapy required)
- Persistent high-grade T1 urothelial carcinoma at repeat TURBT (+/- focal CIS) in the bladder. (No prior intravesical therapy required)
- Restaging TURBT must be performed and must meet ALL of the following criteria below:
- If there is absence of muscularis propria in the initial TURBT, there must be uninvolved muscularis propria in the restaging TURBT.
- All grossly visible papillary tumors must be removed
- Note: If the restaging TURBT is performed outside of the enrolling institution, an office cystoscopy should be performed by a Urologist who will be following the patient as part of the clinical trial
- No pure squamous cell carcinoma or adenocarcinoma of the bladder
- No neuroendocrine (small or large cell) features
- No diffuse carcinoma in situ determined on cystoscopy and biopsy (i.e. extensive carcinoma in situ that is not just tumor-associated CIS in the opinion of the site investigator)
- No prostatic urethral involvement
- Age ≥ 18
- +26 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (125)
AIS Cancer Center at San Joaquin Community Hospital
Bakersfield, California, 93301, United States
Los Angeles General Medical Center
Los Angeles, California, 90033, United States
USC / Norris Comprehensive Cancer Center
Los Angeles, California, 90033, United States
Shaw Cancer Center
Edwards, Colorado, 81632, United States
Helen F Graham Cancer Center
Newark, Delaware, 19713, United States
Medical Oncology Hematology Consultants PA
Newark, Delaware, 19713, United States
UF Health Cancer Institute - Gainesville
Gainesville, Florida, 32610, United States
Mount Sinai Medical Center
Miami Beach, Florida, 33140, United States
Grady Health System
Atlanta, Georgia, 30303, United States
Emory Proton Therapy Center
Atlanta, Georgia, 30308, United States
Emory University Hospital Midtown
Atlanta, Georgia, 30308, United States
Emory University Hospital/Winship Cancer Institute
Atlanta, Georgia, 30322, United States
Emory Saint Joseph's Hospital
Atlanta, Georgia, 30342, United States
Rush MD Anderson Cancer Center
Chicago, Illinois, 60612, 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
Carle Physician Group-Effingham
Effingham, Illinois, 62401, United States
Crossroads Cancer Center
Effingham, Illinois, 62401, United States
Carle Physician Group-Mattoon/Charleston
Mattoon, Illinois, 61938, United States
Carle BroMenn Medical Center
Normal, Illinois, 61761, United States
Carle Cancer Institute Normal
Normal, Illinois, 61761, 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
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
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
Broadlawns Medical Center
Des Moines, Iowa, 50314, 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
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 Kansas Cancer Center
Kansas City, Kansas, 66160, United States
University of Kansas Cancer Center-Overland Park
Overland Park, Kansas, 66210, United States
University of Kansas Hospital-Indian Creek Campus
Overland Park, Kansas, 66211, United States
University of Kansas Hospital-Westwood Cancer Center
Westwood, Kansas, 66205, United States
Louisiana Hematology Oncology Associates LLC
Baton Rouge, Louisiana, 70809, United States
Mary Bird Perkins Cancer Center
Baton Rouge, Louisiana, 70809, United States
Mary Bird Perkins Cancer Center - Gonzales
Gonzales, Louisiana, 70737, United States
Mary Bird Perkins Cancer Center - Metairie
Metairie, Louisiana, 70002, United States
Massachusetts General Hospital Cancer Center
Boston, Massachusetts, 02114, United States
Trinity Health Saint Joseph Mercy Hospital Ann Arbor
Ann Arbor, Michigan, 48106, United States
Trinity Health Medical Center - Brighton
Brighton, Michigan, 48114, United States
Trinity Health Medical Center - Canton
Canton, Michigan, 48188, United States
Chelsea Hospital
Chelsea, Michigan, 48118, United States
University of Michigan Health - Sparrow Lansing
Lansing, Michigan, 48912, United States
Trinity Health Saint Mary Mercy Livonia Hospital
Livonia, Michigan, 48154, United States
Michigan Healthcare Professionals Pontiac
Pontiac, Michigan, 48341, United States
Trinity Health Saint Joseph Mercy Oakland Hospital
Pontiac, Michigan, 48341, United States
Sanford Joe Lueken Cancer Center
Bemidji, Minnesota, 56601, United States
Essentia Health Saint Joseph's Medical Center
Brainerd, Minnesota, 56401, United States
Essentia Health - Deer River Clinic
Deer River, Minnesota, 56636, United States
Essentia Health Cancer Center
Duluth, Minnesota, 55805, United States
Essentia Health Saint Mary's Medical Center
Duluth, Minnesota, 55805, United States
Miller-Dwan Hospital
Duluth, Minnesota, 55805, United States
Essentia Health Hibbing Clinic
Hibbing, Minnesota, 55746, United States
Essentia Health Sandstone
Sandstone, Minnesota, 55072, United States
Essentia Health Virginia Clinic
Virginia, Minnesota, 55792, United States
Saint Francis Medical Center
Cape Girardeau, Missouri, 63703, United States
Parkland Health Center - Farmington
Farmington, Missouri, 63640, United States
University of Kansas Cancer Center - Briarcliff
Kansas City, Missouri, 64116, United States
University of Kansas Cancer Center - North
Kansas City, Missouri, 64154, United States
University of Kansas Cancer Center - Lee's Summit
Lee's Summit, Missouri, 64064, United States
Lake Regional Hospital
Osage Beach, Missouri, 65065, United States
Sainte Genevieve County Memorial Hospital
Sainte Genevieve, Missouri, 63670, United States
Mercy Hospital South
St Louis, Missouri, 63128, United States
Missouri Baptist Medical Center
St Louis, Missouri, 63131, United States
Mercy Hospital Saint Louis
St Louis, Missouri, 63141, United States
Missouri Baptist Sullivan Hospital
Sullivan, Missouri, 63080, United States
BJC Outpatient Center at Sunset Hills
Sunset Hills, Missouri, 63127, United States
Memorial Sloan Kettering Basking Ridge
Basking Ridge, New Jersey, 07920, United States
Memorial Sloan Kettering Monmouth
Middletown, New Jersey, 07748, United States
Memorial Sloan Kettering Bergen
Montvale, New Jersey, 07645, United States
Memorial Sloan Kettering Commack
Commack, New York, 11725, United States
Memorial Sloan Kettering Westchester
Harrison, New York, 10604, United States
Memorial Sloan Kettering Cancer Center
New York, New York, 10065, United States
Memorial Sloan Kettering Nassau
Uniondale, New York, 11553, United States
UNC Lineberger Comprehensive Cancer Center
Chapel Hill, North Carolina, 27599, United States
Sanford Broadway Medical Center
Fargo, North Dakota, 58122, United States
Sanford Roger Maris Cancer Center
Fargo, North Dakota, 58122, United States
Riverside Methodist Hospital
Columbus, Ohio, 43214, United States
Grant Medical Center
Columbus, Ohio, 43215, United States
Doctors Hospital
Columbus, Ohio, 43228, United States
Dublin Methodist Hospital
Dublin, Ohio, 43016, United States
OhioHealth Mansfield Hospital
Mansfield, Ohio, 44903, United States
OhioHealth Marion General Hospital
Marion, Ohio, 43302, United States
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, 73104, United States
Christiana Care Health System-Concord Health Center
Chadds Ford, Pennsylvania, 19317, United States
Geisinger Medical Center
Danville, Pennsylvania, 17822, United States
Geisinger Cancer Center Dickson City
Dickson City, Pennsylvania, 18519, United States
UPMC Hillman Cancer Center Erie
Erie, Pennsylvania, 16505, United States
UPMC Cancer Center at UPMC Horizon
Farrell, Pennsylvania, 16121, United States
UPMC Cancer Centers - Arnold Palmer Pavilion
Greensburg, Pennsylvania, 15601, United States
Penn State Milton S Hershey Medical Center
Hershey, Pennsylvania, 17033-0850, United States
Geisinger Medical Oncology-Lewisburg
Lewisburg, Pennsylvania, 17837, United States
UPMC Cancer Center - Monroeville
Monroeville, Pennsylvania, 15146, United States
UPMC Hillman Cancer Center - Monroeville
Monroeville, Pennsylvania, 15146, United States
UPMC Hillman Cancer Center - New Castle
New Castle, Pennsylvania, 16105, United States
UPMC-Saint Margaret
Pittsburgh, Pennsylvania, 15215, United States
University of Pittsburgh Cancer Institute (UPCI)
Pittsburgh, Pennsylvania, 15232, United States
UPMC-Shadyside Hospital
Pittsburgh, Pennsylvania, 15232, United States
UPMC-Passavant Hospital
Pittsburgh, Pennsylvania, 15237, United States
UPMC Cancer Center at UPMC Northwest
Seneca, Pennsylvania, 16346, United States
UPMC Cancer Center-Washington
Washington, Pennsylvania, 15301, United States
UPMC Washington Hospital Radiation Oncology
Washington, Pennsylvania, 15301, United States
Geisinger Wyoming Valley/Henry Cancer Center
Wilkes-Barre, Pennsylvania, 18711, United States
Central Vermont Medical Center/National Life Cancer Treatment
Berlin Corners, Vermont, 05602, United States
University of Vermont Medical Center
Burlington, Vermont, 05401, United States
University of Vermont and State Agricultural College
Burlington, Vermont, 05405, United States
Bon Secours Memorial Regional Medical Center
Mechanicsville, Virginia, 23116, United States
Bon Secours Saint Francis Medical Center
Midlothian, Virginia, 23114, United States
Bon Secours Saint Mary's Hospital
Richmond, Virginia, 23226, United States
Bon Secours Cancer Institute at Reynolds Crossing
Richmond, Virginia, 23230, United States
VCU Massey Comprehensive Cancer Center
Richmond, Virginia, 23298, United States
VCU Community Memorial Health Center
South Hill, Virginia, 23970, United States
West Virginia University Healthcare
Morgantown, West Virginia, 26506, United States
Duluth Clinic Ashland
Ashland, Wisconsin, 54806, United States
Northwest Wisconsin Cancer Center
Ashland, Wisconsin, 54806, United States
The Research Institute of the McGill University Health Centre (MUHC)
Montreal, Quebec, H3H 2R9, Canada
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Brian C Baumann
NRG Oncology
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
January 9, 2025
First Posted
January 13, 2025
Study Start
June 3, 2025
Primary Completion (Estimated)
February 1, 2032
Study Completion (Estimated)
February 1, 2032
Last Updated
May 6, 2026
Record last verified: 2025-12
Data Sharing
- IPD Sharing
- Will share
NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.