Randomized Phase II Trial of Pembrolizumab and Radiation vs. Radiation and Concurrent Chemotherapy for High-Grade T1 Bladder Cancer (PARRC Trial)

Status: Recruiting
Location: See all (74) locations...
Intervention Type: Procedure, Drug, Other, Radiation, Biological
Study Type: Interventional
Study Phase: Phase 2
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.

Eligibility
Participation Requirements
Sex: All
Minimum Age: 18
Healthy Volunteers: f
View:

• 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

• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2

• Negative urine or serum pregnancy test (in persons of childbearing potential) within 14 days prior to registration. Childbearing potential is defined as any person who has experienced menarche and who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy), tubal ligation or who is not postmenopausal

• Absolute neutrophil count (ANC) ≥ 1,500 cells/mm\^3

• Platelets ≥ 100,000 cells/mm\^3

• Hemoglobin ≥ 9 g/dl (Note: The use of transfusion or other intervention to achieve hemoglobin \[Hgb\] ≥ 9 g/dl is acceptable)

• Adequate renal function defined as creatinine clearance (CrCL) of ≥ 30 mL/min by the Cockcroft-Gault formula, ≤ 1.5 × upper limit of normal (ULN) or creatinine levels \> 1.5 × institutional ULN

• Total bilirubin ≤ institutional upper limit of normal (ULN) (Not applicable to patients with known Gilbert's syndrome)

• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\]) and alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase \[SGPT\]) ≤ 3 x institutional ULN

• All adverse events of their most recent therapy/intervention must have resolved to \< grade 3 or returned to baseline prior to registration

• No history of pelvic radiation therapy

• No prior systemic chemotherapy or immunotherapy for urothelial carcinoma. Prior treatment with local intravesical therapy including BCG or chemotherapy is allowed

• No prior treatment with anti-PD-1, anti PD-L1, anti PD-L2 or anti-CTLA4 antibody or any other antibody or drug targeting T-cell co-stimulation

• No live vaccine administered within 30 days of registration. All non live vaccines (including the coronavirus disease \[COVID\] vaccine) are allowed at any time during the study. Timing should minimize confusion with drug-related toxicities where possible

• Patients must have recovered from acute cardiac illness

• New York Heart Association Functional Classification II or better (New York Heart Association \[NYHA\] Functional Classification III/IV are not eligible) (Note: 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.)

• No active infection requiring IV antibiotics

• No active autoimmune disease that required systemic treatment in the past 2 years (i.e., with use of disease modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment

• No history of idiopathic pulmonary fibrosis, organizing pneumonia, (non-infectious) pneumonitis that required steroids or current pneumonitis

• No history of allogeneic bone marrow transplant or prior solid organ transplant

• No active tuberculosis

• No evidence of hydronephrosis

• No history of upper tract urothelial carcinoma within 24 months of registration

• No patients with a prior diagnosis of prostate cancer who have not received definitive treatment for their prostate cancer (e.g. on active surveillance)

• Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial

• No glucocorticoids except physiologic doses are allowed. The use of doses of corticosteroids (defined as 10 mg prednisone or equivalent) is acceptable

• No history of allergic reaction to the drug excipients

Locations
United States
California
AIS Cancer Center at San Joaquin Community Hospital
RECRUITING
Bakersfield
Los Angeles General Medical Center
RECRUITING
Los Angeles
USC / Norris Comprehensive Cancer Center
RECRUITING
Los Angeles
Colorado
Shaw Cancer Center
RECRUITING
Edwards
Delaware
Helen F Graham Cancer Center
RECRUITING
Newark
Medical Oncology Hematology Consultants PA
RECRUITING
Newark
Florida
University of Florida Health Science Center - Gainesville
RECRUITING
Gainesville
Iowa
Mary Greeley Medical Center
RECRUITING
Ames
McFarland Clinic - Ames
RECRUITING
Ames
Illinois
Rush University Medical Center
RECRUITING
Chicago
Cancer Care Specialists of Illinois - Decatur
RECRUITING
Decatur
Decatur Memorial Hospital
RECRUITING
Decatur
Crossroads Cancer Center
RECRUITING
Effingham
Southern Illinois University School of Medicine
RECRUITING
Springfield
Springfield Clinic
RECRUITING
Springfield
Springfield Memorial Hospital
RECRUITING
Springfield
Kansas
University of Kansas Cancer Center
RECRUITING
Kansas City
University of Kansas Cancer Center-Overland Park
RECRUITING
Overland Park
University of Kansas Hospital-Indian Creek Campus
RECRUITING
Overland Park
University of Kansas Hospital-Westwood Cancer Center
RECRUITING
Westwood
Louisiana
Louisiana Hematology Oncology Associates LLC
RECRUITING
Baton Rouge
Mary Bird Perkins Cancer Center
RECRUITING
Baton Rouge
Mary Bird Perkins Cancer Center - Gonzales
RECRUITING
Gonzales
Mary Bird Perkins Cancer Center - Metairie
RECRUITING
Metairie
Minnesota
Sanford Joe Lueken Cancer Center
RECRUITING
Bemidji
Essentia Health Saint Joseph's Medical Center
RECRUITING
Brainerd
Essentia Health - Deer River Clinic
RECRUITING
Deer River
Essentia Health Cancer Center
RECRUITING
Duluth
Essentia Health Saint Mary's Medical Center
RECRUITING
Duluth
Miller-Dwan Hospital
RECRUITING
Duluth
Essentia Health Hibbing Clinic
RECRUITING
Hibbing
Essentia Health Sandstone
RECRUITING
Sandstone
Essentia Health Virginia Clinic
RECRUITING
Virginia
Missouri
Saint Francis Medical Center
RECRUITING
Cape Girardeau
Parkland Health Center - Farmington
RECRUITING
Farmington
University of Kansas Cancer Center - North
RECRUITING
Kansas City
University of Kansas Cancer Center - Lee's Summit
RECRUITING
Lee's Summit
Lake Regional Hospital
RECRUITING
Osage Beach
Sainte Genevieve County Memorial Hospital
RECRUITING
Sainte Genevieve
Mercy Hospital Saint Louis
RECRUITING
St Louis
Mercy Hospital South
RECRUITING
St Louis
Missouri Baptist Medical Center
RECRUITING
St Louis
Missouri Baptist Sullivan Hospital
RECRUITING
Sullivan
BJC Outpatient Center at Sunset Hills
RECRUITING
Sunset Hills
North Carolina
UNC Lineberger Comprehensive Cancer Center
RECRUITING
Chapel Hill
North Dakota
Sanford Broadway Medical Center
RECRUITING
Fargo
Sanford Roger Maris Cancer Center
RECRUITING
Fargo
Oklahoma
University of Oklahoma Health Sciences Center
RECRUITING
Oklahoma City
Pennsylvania
Christiana Care Health System-Concord Health Center
RECRUITING
Chadds Ford
UPMC Hillman Cancer Center Erie
RECRUITING
Erie
UPMC Cancer Center at UPMC Horizon
RECRUITING
Farrell
UPMC Cancer Centers - Arnold Palmer Pavilion
RECRUITING
Greensburg
Penn State Milton S Hershey Medical Center
RECRUITING
Hershey
Geisinger Medical Oncology-Lewisburg
RECRUITING
Lewisburg
UPMC Cancer Center - Monroeville
RECRUITING
Monroeville
UPMC Hillman Cancer Center - Monroeville
RECRUITING
Monroeville
UPMC Hillman Cancer Center - New Castle
RECRUITING
New Castle
University of Pittsburgh Cancer Institute (UPCI)
RECRUITING
Pittsburgh
UPMC-Passavant Hospital
RECRUITING
Pittsburgh
UPMC-Saint Margaret
RECRUITING
Pittsburgh
UPMC-Shadyside Hospital
RECRUITING
Pittsburgh
UPMC Cancer Center at UPMC Northwest
RECRUITING
Seneca
UPMC Cancer Center-Washington
RECRUITING
Washington
UPMC Washington Hospital Radiation Oncology
RECRUITING
Washington
Geisinger Wyoming Valley/Henry Cancer Center
RECRUITING
Wilkes-barre
Virginia
Bon Secours Memorial Regional Medical Center
RECRUITING
Mechanicsville
Bon Secours Saint Francis Medical Center
RECRUITING
Midlothian
Bon Secours Cancer Institute at Reynolds Crossing
RECRUITING
Richmond
Bon Secours Saint Mary's Hospital
RECRUITING
Richmond
VCU Massey Comprehensive Cancer Center
RECRUITING
Richmond
VCU Community Memorial Health Center
RECRUITING
South Hill
Wisconsin
Duluth Clinic Ashland
RECRUITING
Ashland
Northwest Wisconsin Cancer Center
RECRUITING
Ashland
West Virginia
West Virginia University Healthcare
RECRUITING
Morgantown
Time Frame
Start Date: 2025-06-03
Estimated Completion Date: 2032-02-01
Participants
Target number of participants: 160
Treatments
Active_comparator: Arm 1 (Chemotherapy and radiation)
Patients 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.
Experimental: Arm 2 (Pembrolizumab and radiation)
Patients 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.
Related Therapeutic Areas
Sponsors
Leads: National Cancer Institute (NCI)

This content was sourced from clinicaltrials.gov

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