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NCT06770582

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

Last Updated: 2025-11-13

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE2

Total Enrollment

160 participants

Study Classification

INTERVENTIONAL

Study Start Date

2025-06-03

Study Completion Date

2032-02-01

Brief Summary

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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.

Detailed Description

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PRIMARY OBJECTIVE:

I. To compare bladder-intact event-free survival.

SECONDARY OBJECTIVES:

I. To assess complete response by cystoscopy at 6 months. II. To assess disease-free survival. III. To assess local-regional control. IV. To assess metastasis-free survival. V. To assess overall survival. VI. To assess quality of life using European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) and the Bladder Cancer Index at 18 months.

VII. To assess Common Terminology Criteria for Adverse Events (CTCAE) adverse events (both acute and late).

EXPLORATORY OBJECTIVES:

I. To assess fatigue using the Patient Reported Outcomes Measurement Information System Fatigue-4A (PROMIS-Fatigue-4a).

II. To assess quality adjusted survival using European Quality of Life Five Dimension Five Level Scale (EQ-5D-5L).

III. To assess cumulative quality of life using EORTC QLC-C30 and Bladder Cancer Index at 24 months.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM 1: Patients receive one of the following chemotherapy regimens per physicians choice: 1) cisplatin intravenously (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 computed tomography (CT)/magnetic resonance imaging (MRI) and blood sample collection throughout the study. Patients may also undergo optional urine sample collection on study.

ARM 2: 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.

After completion of study treatment, patients are followed up every 3 months for 2 years, then every 6 months for 3 years and then annually for 5 years.

Conditions

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Non-Muscle Invasive Bladder Urothelial Carcinoma Recurrent Non-Muscle Invasive Bladder Urothelial Carcinoma Stage I Bladder Cancer AJCC v8

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type ACTIVE_COMPARATOR

Biospecimen Collection

Intervention Type PROCEDURE

Undergo blood and urine sample collection

Cisplatin

Intervention Type DRUG

Given IV

Computed Tomography

Intervention Type PROCEDURE

Undergo CT

Fluorouracil

Intervention Type DRUG

Given IV

Gemcitabine

Intervention Type DRUG

Given IV

Magnetic Resonance Imaging

Intervention Type PROCEDURE

Undergo MRI

Mitomycin

Intervention Type DRUG

Given IV

Questionnaire Administration

Intervention Type OTHER

Ancillary studies

Radiation Therapy

Intervention Type RADIATION

Undergo radiation therapy

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.

Group Type EXPERIMENTAL

Biospecimen Collection

Intervention Type PROCEDURE

Undergo blood and urine sample collection

Computed Tomography

Intervention Type PROCEDURE

Undergo CT

Magnetic Resonance Imaging

Intervention Type PROCEDURE

Undergo MRI

Pembrolizumab

Intervention Type BIOLOGICAL

Given IV

Questionnaire Administration

Intervention Type OTHER

Ancillary studies

Radiation Therapy

Intervention Type RADIATION

Undergo radiation therapy

Interventions

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Biospecimen Collection

Undergo blood and urine sample collection

Intervention Type PROCEDURE

Cisplatin

Given IV

Intervention Type DRUG

Computed Tomography

Undergo CT

Intervention Type PROCEDURE

Fluorouracil

Given IV

Intervention Type DRUG

Gemcitabine

Given IV

Intervention Type DRUG

Magnetic Resonance Imaging

Undergo MRI

Intervention Type PROCEDURE

Mitomycin

Given IV

Intervention Type DRUG

Pembrolizumab

Given IV

Intervention Type BIOLOGICAL

Questionnaire Administration

Ancillary studies

Intervention Type OTHER

Radiation Therapy

Undergo radiation therapy

Intervention Type RADIATION

Other Intervention Names

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Biological Sample Collection Biospecimen Collected Specimen Collection Abiplatin Blastolem Briplatin CDDP Cis-diammine-dichloroplatinum Cis-diamminedichloridoplatinum Cis-diamminedichloro Platinum (II) Cis-diamminedichloroplatinum Cis-dichloroammine Platinum (II) Cis-platinous Diamine Dichloride Cis-platinum Cis-platinum II Cis-platinum II Diamine Dichloride Cismaplat Cisplatina Cisplatinum Cisplatyl Citoplatino Citosin Cysplatyna DDP Lederplatin Metaplatin Neoplatin Peyrone's Chloride Peyrone's Salt Placis Plastistil Platamine Platiblastin Platiblastin-S Platinex Platinol Platinol- AQ Platinol-AQ Platinol-AQ VHA Plus Platinoxan Platinum Platinum Diamminodichloride Platiran Platistin Platosin CAT CAT Scan Computed Axial Tomography Computerized Axial Tomography Computerized axial tomography (procedure) Computerized Tomography Computerized Tomography (CT) scan CT CT Scan Diagnostic CAT Scan Diagnostic CAT Scan Service Type tomography 5 Fluorouracil 5 Fluorouracilum 5 FU 5-Fluoro-2,4(1H, 3H)-pyrimidinedione 5-Fluorouracil 5-Fluracil 5-Fu 5FU AccuSite Carac Fluoro Uracil Fluouracil Flurablastin Fluracedyl Fluracil Fluril Fluroblastin Ribofluor Ro 2-9757 Ro-2-9757 dFdC dFdCyd Difluorodeoxycytidine Magnetic Resonance Magnetic Resonance Imaging (MRI) Magnetic resonance imaging (procedure) Magnetic Resonance Imaging Scan Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance MR MR Imaging MRI MRI Scan MRIs NMR Imaging NMRI Nuclear Magnetic Resonance Imaging sMRI Structural MRI Ametycine Jelmyto MITO Mito-C Mito-Medac Mitocin Mitocin-C Mitolem Mitomycin C Mitomycin pyelocalyceal Mitomycin-C Mitomycin-X Mitomycine C Mitosol Mitozytrex Mutamycin Mutamycine NCI-C04706 BCD-201 GME 751 GME751 Keytruda Lambrolizumab MK 3475 MK-3475 MK3475 Pembrolizumab Biosimilar BCD-201 Pembrolizumab Biosimilar GME751 Pembrolizumab Biosimilar QL2107 Pembrolizumab Biosimilar RPH-075 Pembrolizumab Biosimilar SB27 QL2107 RPH 075 RPH-075 RPH075 SB 27 SB-27 SB27 SCH 900475 SCH-900475 SCH900475 Cancer Radiotherapy Energy Type ENERGY_TYPE Irradiate Irradiated Irradiation Radiation Radiation Therapy, NOS Radiotherapeutics Radiotherapy RT Therapy, Radiation

Eligibility Criteria

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Inclusion Criteria

* 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

Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Brian C Baumann

Role: PRINCIPAL_INVESTIGATOR

NRG Oncology

Locations

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AIS Cancer Center at San Joaquin Community Hospital

Bakersfield, California, United States

Site Status RECRUITING

Los Angeles General Medical Center

Los Angeles, California, United States

Site Status RECRUITING

USC / Norris Comprehensive Cancer Center

Los Angeles, California, United States

Site Status RECRUITING

Shaw Cancer Center

Edwards, Colorado, United States

Site Status RECRUITING

Helen F Graham Cancer Center

Newark, Delaware, United States

Site Status RECRUITING

Medical Oncology Hematology Consultants PA

Newark, Delaware, United States

Site Status RECRUITING