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.
Participants must have histologic evidence of cT2-T4aN0M0 muscle invasive urothelial carcinoma of the bladder within 180 days prior to starting neoadjuvant therapy (NAT)
Participants must have had CT chest/abdomen/pelvis (C/A/P), MRI C/A/P or PET within 60 days prior to starting NAT to determine cT2-T4aN0M0
Participants must have undergone TURBT with biopsy of areas of prior disease and systematic biopsies (left and right lateral, dome, posterior wall and trigone) and radiologic staging showing clinically T0-T1 disease within 60 days after the last dose of NAT. At least 4 out of 5 systematic biopsies must be performed
NOTE: This TURBT must be within 90 days prior to registration. Registration must be within 90 days after the last dose of NAT
None
Single group
Biospecimen Collection
Procedure/SurgeryUndergo tissue, urine, and blood sample collection
Computed Tomography
Procedure/SurgeryUndergo CT
Cystoscopy
Procedure/SurgeryUndergo cystoscopy
Magnetic Resonance Imaging
Procedure/SurgeryUndergo MRI
Pembrolizumab
Biological/VaccineGiven IV
Photon Beam Radiation Therapy
RadiationUndergo photon beam RT
Positron Emission Tomography
Procedure/SurgeryUndergo PET
Questionnaire Administration
Other interventionAncillary studies
Transurethral Resection of Bladder Tumor
Procedure/SurgeryUndergo TURBT
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.
BI-EFS
Local muscle invasive recurrence-free survival
Metastasis-free survival
Overall survival
Patient reported adverse events
Selected Patient Reported Outcomes (PRO)-CTCAE questions will be used to assess patient-reported symptoms. For each of the PRO-CTCAE adverse events examined, the scores for each attribute (frequency, severity and/or interference) will be presented descriptively using summary statistics at each assessment time. Additionally, the worst level of frequency, severity and/or interference over the entire course will be summarized. The proportion of patients by arm experiencing a maximum follow-up PRO-CTCAE score greater than 0 (reflecting any evidence of a given symptom) or 3 or higher (reflecting "frequent" or worse, "severe" or worse, or "quite a bit" or worse of frequency, severity, and interference items, respectively), both unadjusted and adjusted for the baseline PRO-CTCAE score, will be reported.
Click on the lead sponsor to view all of their trials.
