This phase II trial compares the effect of adding radiation therapy to an immunotherapy drug called pembrolizumab versus pembrolizumab alone in treating patients with urothelial cancer that has spread from where it first started (primary site) to other places in the body (metastatic). The addition of radiation to immunotherapy may shrink the cancer, but it could also cause side effects. 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. Stereotactic body radiation therapy (SBRT) is a type of radiation therapy that uses high energy x-rays to kill tumor cells and shrink tumors. This method uses special equipment to position a patient and precisely deliver radiation to tumors with high precision. This method may kill tumor cells with fewer doses over a shorter period and may cause less damage to normal tissue than conventional radiation therapy. The combination of pembrolizumab and radiation therapy may be more efficient in killing tumor cells.
PRIMARY OBJECTIVE: I. To compare the overall response rates by 6 months in patients with advanced urothelial carcinoma when treated with immunotherapy alone and immunotherapy plus radiotherapy to a single site. SECONDARY OBJECTIVES: I. To compare the response rates using immune related Response Evaluation Criteria in Solid Tumors (iRECIST) as assessed by central review. II. To compare progression-free survival (PFS) and overall survival (OS) for patients treated with immunotherapy and immunotherapy plus radiotherapy. III. To compare the rates of treatment discontinuation at 1 year. IV. To assess adverse events experienced by patients treated with immunotherapy and immunotherapy plus radiotherapy via the Common Terminology Criteria for Adverse Events (CTCAE) and Patient Reported Outcome (PRO)-CTCAE. IV. To determine whether treatment effects are similar for key subgroups including those defined by the stratification variables. QUALITY OF LIFE CORRELATIVE STUDY OBJECTIVES: I. To compare patient-reported fatigue as assessed by the Patient Reported Outcomes Measurement Information System (PROMIS)-Fatigue 8a from baseline through 24 months between patients treated with immunotherapy alone and immunotherapy plus radiotherapy to a single site. II. To compare health-related quality of life (HRQOL) as assessed by the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-Core (C)30 from baseline through 24 months between patients treated with immunotherapy alone and immunotherapy plus radiotherapy to a single site. III. To compare urinary symptoms as assessed by the EORTC QLQ-BLM30 from baseline through 24 months between patients treated with immunotherapy alone and immunotherapy plus radiotherapy to a single site. IV. To compare patient-reported diarrhea, shortness of breath and pain as assessed by the EORTC QLQ-C30 from baseline through 24 months between patients treated with immunotherapy alone and immunotherapy plus radiotherapy to a single site. V. To compare health utilities and quality-adjusted survival between patients treated with immunotherapy alone and immunotherapy plus radiotherapy to a single site. VI. To compare other scale scores of the EORTC QLQ-C30 (global health status and quality of life; physical, role, emotional, cognitive, and social function; symptoms) and EORTC QLQ-BLM30 (urostomy problems, catheter problems, future perspectives, abdominal bloating and flatulence, body image, sexual function) at 45 days, and at 6, 12, and 24 months between patients treated with immunotherapy alone and immunotherapy plus radiotherapy to a single site. OUTLINE: Patients are randomized to 1 of 2 arms. ARM A: Patients receive pembrolizumab intravenously (IV) over 25-40 minutes on day 1 of each cycle. Cycles repeat every 3 weeks in the absence of disease progression or unacceptable toxicity. Patients undergo computed tomography (CT) scan, magnetic resonance imaging (MRI), bone scan and/or positron emission tomography (PET) scan, as well as optional urine and blood sample collection throughout the study. ARM B: Patients receive pembrolizumab as in Arm A. Patients also undergo SBRT once daily (QD) every other day for 3 fractions over 2 weeks that must be completed before 12 weeks after the first dose of pembrolizumab in the absence of disease progression or unacceptable toxicity. Patients undergo CT scan, MRI, bone scan, and/or PET scan, as well as optional urine and blood sample collection throughout the study. After completion of study treatment, patients are followed up within 12 weeks and then every 3 months for 3 years following registration.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
1
Undergo urine and blood sample collection
Undergo bone scan
Undergo CT scan
Undergo MRI
Given IV
Undergo PET scan
Ancillary studies
Undergo SBRT
Littleton Adventist Hospital
Littleton, Colorado, United States
Illinois CancerCare-Bloomington
Bloomington, Illinois, United States
Illinois CancerCare-Canton
Canton, Illinois, United States
Illinois CancerCare-Carthage
Carthage, Illinois, United States
Centralia Oncology Clinic
Centralia, Illinois, United States
Tumor Response
Will be defined as a complete response (CR) or partial response (PR) as assessed by the treating physician using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 criteria.
Time frame: Up to 6 months from randomization
Tumor Response
Will be determined to have a tumor response if they have a CR or PR as assessed by immune modified RECIST.
Time frame: Up to 3 years from randomization
Progression-free Survival
Stratified Cox models will be used to compare the outcomes between the two treatment groups. The results will be summarized with a forest plot displaying the estimate of the hazard ratio and corresponding 95% confidence interval.
Time frame: Time from randomization until disease progression as assessed by the treating physician using RECIST 1.1 or death due to any cause, assessed up to 3 years
Overall Survival
Stratified Cox models will be used to compare the outcomes between the two treatment groups. The results will be summarized with a forest plot displaying the estimate of the hazard ratio and corresponding 95% confidence interval.
Time frame: Time from randomization until death due to any cause. Patients who are not known to be dead at time of analysis will be censored at the time of their last follow-up, assessed up to 3 years
Rate of Treatment Discontinuation
The proportion of patients who discontinue their protocol directed treatment prior to one year from date of study registration will be determined. Patients who stop their protocol directed treatment for any reason prior to one year from study registration will be considered to have discontinued their treatment. The rates of treatment discontinuation at one year will be summarized with a binomial point estimate and corresponding 95% confidence interval by arm. A comparison between the rates will be performed with a chi-square test or a Fisher's exact test if the assumptions of the chi-square test are violated.
Time frame: At 1 year
Incidence of Adverse Events
Will be assessed by Common Terminology Criteria for Adverse Events version 5.0. Adverse events will be summarized with frequencies and relative frequencies.
Time frame: Up to 3 years from randomization
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Rush University Medical Center
Chicago, Illinois, United States
University of Illinois
Chicago, Illinois, United States
Carle at The Riverfront
Danville, Illinois, United States
Cancer Care Specialists of Illinois - Decatur
Decatur, Illinois, United States
Decatur Memorial Hospital
Decatur, Illinois, United States
...and 73 more locations