This phase II trial tests the effect of giving pembrolizumab in combination with radiation therapy after chemotherapy in preventing surgery to remove the bladder in patients with muscle invasive bladder cancer. Standard of care therapy includes chemotherapy before surgery (neoadjuvant) to shrink or get rid of the tumor. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the tumor, and may interfere with the ability of tumor cells to grow and spread. Radiation therapy uses high energy x-rays, particles, or radioactive seeds to kill cancer cells and shrink tumors. Photon beam radiation therapy is a type of radiation therapy that uses x-rays or gamma rays that come from a special machine called a linear accelerator. The radiation dose is delivered at the surface of the body and goes into the tumor and through the body. Giving pembrolizumab in combination with radiation therapy after neoadjuvant chemotherapy may help prevent surgical removal of the bladder in patients with muscle invasive bladder cancer.
PRIMARY OBJECTIVE: I. To evaluate whether 3-year bladder intact event-free survival (BI-EFS) is at least 70% in participants with clinically T0-clinically T1 without multifocal carcinoma in situ (CIS) following neoadjuvant therapy (NAT) for muscle-invasive bladder cancer (MIBC) who receive radiotherapy (RT) + pembrolizumab (MK-3475). SECONDARY OBJECTIVES: I. To estimate BI-EFS in participants who receive RT + pembrolizumab (MK-3475). II. To estimate local muscle invasive recurrence-free survival in participants who receive RT+ pembrolizumab (MK-3475). III. To estimate the metastasis-free survival (MFS) in participants who receive RT+ pembrolizumab (MK-3475). IV. To estimate the overall survival (OS) in participants who receive RT + pembrolizumab (MK-3475). V. To estimate the rate of salvage cystectomy in participants who receive RT+ pembrolizumab (MK-3475). VI. To evaluate the frequency and severity of toxicities in participants who receive RT + pembrolizumab (MK-3475). PATIENT REPORTED OUTCOMES (PRO)-COMMON TERMINOLOGY CRITERIA FOR ADVERSE EVENTS (CTCAE) OBJECTIVE: I. To evaluate participant-reported symptoms using selected items from Gastrointestinal, Genitourinary and sexual function domains of the PRO-CTCAE, with the goal of characterizing the frequency, severity, and interference of treatment-related symptoms. BANKING OBJECTIVE: I. To bank specimens for future correlative studies. OUTLINE: Patients undergo photon beam RT once daily (QD) on Monday-Friday for up to 20 treatments and receive pembrolizumab intravenously (IV) over 30 minutes on day 1 of each cycle. Cycles repeat every 21 days for up to 18 cycles (for a total of 12 months, including NAT) in the absence of disease progression or unacceptable toxicity. Patients also undergo transurethral resection of bladder tumor (TURBT) with tissue sample collection at pre-registration and computed tomography (CT), magnetic resonance imaging (MRI) or positron emission tomography (PET), cystoscopy, and urine and blood sample collection throughout the study. After completion of study treatment, patients are followed every 26 weeks until year 2 and then every 52 weeks up to year 5.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
111
Undergo tissue, urine, and blood sample collection
Undergo CT
Undergo cystoscopy
Undergo MRI
Given IV
Undergo photon beam RT
Undergo PET
Ancillary studies
Undergo TURBT
University of Alabama at Birmingham Cancer Center
Birmingham, Alabama, United States
RECRUITINGMayo Clinic Hospital in Arizona
Phoenix, Arizona, United States
RECRUITINGTower Cancer Research Foundation
Beverly Hills, California, United States
RECRUITINGCity of Hope Corona
Corona, California, United States
Bladder intact event-free survival (BI-EFS)
Will be evaluated as the percentage of participants who do not experience a BI-EFS event using a Kaplan-Meier estimate. A single-arm test of proportions will be used to test against the null hypothesis (true BI-EFS = 55%). Standard errors will be calculated using Greenwood's formula. If the upper bound of the one-sided 90% confidence interval includes 70%, then the radiation therapy + pembrolizumab regimen will be concluded to be active in this population.
Time frame: Within 3 years after registration
BI-EFS
Time frame: From registration to the first documentation of a BI-EFS event, assessed up to 5 years
Local muscle invasive recurrence-free survival
Time frame: From date of registration to first radiologic or histologic evidence of local muscle invasive bladder carcinoma recurrence, assessed up to 5 years
Metastasis-free survival
Time frame: From date of registration to first radiologic or histologic evidence of metastatic disease or death due to any cause, assessed up to 5 years
Overall survival
Time frame: From date of registration to date of death due to any cause, assessed up to 5 years
Salvage cystectomy
Will be defined as the number of participants that undergo a radical cystectomy.
Time frame: Up to 5 years
Incidence of adverse events
Will be assessed using National Cancer Institute CTCAE version 5.0.
Time frame: Up to 30 days after last dose of study treatment
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City of Hope Comprehensive Cancer Center
Duarte, California, United States
RECRUITINGCity of Hope at Irvine Lennar
Irvine, California, United States
RECRUITINGCity of Hope Antelope Valley
Lancaster, California, United States
RECRUITINGLos Angeles General Medical Center
Los Angeles, California, United States
RECRUITINGUSC / Norris Comprehensive Cancer Center
Los Angeles, California, United States
RECRUITINGCedars Sinai Medical Center
Los Angeles, California, United States
RECRUITING...and 102 more locations