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

What this study is about

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.

Who can join (things the study team will check)

✅ You may be able to join 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
• 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

+ 14 more criteria — see the full checklist in the app.

Where this trial is running

• Highlands Oncology Group - Fayetteville, Fayetteville, Arkansas, United States
• Highlands Oncology Group - Rogers, Rogers, Arkansas, United States
• Highlands Oncology Group, Springdale, Arkansas, United States
• AIS Cancer Center at San Joaquin Community Hospital, Bakersfield, California, United States
• Los Angeles General Medical Center, Los Angeles, California, United States
• USC / Norris Comprehensive Cancer Center, Los Angeles, California, United States
• Shaw Cancer Center, Edwards, Colorado, United States
• Helen F Graham Cancer Center, Newark, Delaware, United States
• Medical Oncology Hematology Consultants PA, Newark, Delaware, United States
• UF Health Cancer Institute - Gainesville, Gainesville, Florida, United States
• Mount Sinai Medical Center, Miami Beach, Florida, United States
• Grady Health System, Atlanta, Georgia, United States

+ 122 more sites.