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Consolidative Therapy After EV + Pembrolizumab in Muscle Invasive Bladder Cancer, REINFORCE Trial
Sponsor: University of Washington
Summary
This phase I/II clinical trial is evaluating a novel treatment strategy for patients with advanced bladder cancer that is unresectable, has spread to nearby lymph nodes or a limited number of distant sites (oligometastatic disease), and has responded to initial treatment with enfortumab vedotin and pembrolizumab. Although this combination has significantly improved outcomes compared to traditional chemotherapy, many patients are left with residual cancer in the bladder or other sites, and there is currently no established standard approach for managing this remaining disease or determining the optimal duration of systemic therapy. Prolonged treatment can lead to cumulative side effects and negatively impact quality of life. This study investigates whether adding consolidative treatment-such as radiation therapy to the bladder and metastatic sites or surgical removal of the bladder (radical cystectomy)-can safely eliminate residual disease and delay cancer progression. Radiation therapy uses high-energy x-rays to precisely target and destroy cancer cells while minimizing exposure to surrounding normal tissues. In selected patients, surgery may be used to remove remaining tumor in the bladder. Targeted radiation techniques, such as stereotactic body radiation therapy (SBRT), may also be used to treat small metastatic sites. This approach may allow for safe discontinuation of systemic therapy, potentially reducing long-term treatment-related side effects. A key component of this trial is the integration of biomarker testing using circulating tumor DNA (ctDNA) from blood and urine tumor DNA (utDNA). These tests detect small amounts of tumor-derived genetic material and may help identify patients most likely to benefit from consolidative treatment, as well as guide decisions about ongoing therapy. By combining response to systemic therapy with personalized local treatment and biomarker-driven monitoring, this study aims to improve cancer control, reduce complications from untreated local disease, and inform future treatment strategies for patients with advanced bladder cancer.
Official title: Consolidative Radiation Therapy or Cystectomy After Initial Favorable Response Succeeding Enfortumab Vedotin Plus Pembrolizumab (REINFORCE)--- A Phase I/II Pilot Feasibility Trial
Key Details
Gender
All
Age Range
18 Years - Any
Study Type
INTERVENTIONAL
Enrollment
12
Start Date
2026-06-01
Completion Date
2029-12-31
Last Updated
2026-05-14
Healthy Volunteers
No
Conditions
Interventions
Intensity-Modulated Radiation Therapy
Undergo IMRT
Volume Modulated Arc Therapy
Undergo VMAT
Cisplatin
Given IV
Gemcitabine
Given IV
Fluorouracil
Given fluorouracil
Mitomycin
Given mitomycin
Radical Cystectomy
Undergo radical cystectomy
Pelvic Lymphadenectomy
Undergo pelvic lymph node dissection
Stereotactic Body Radiation Therapy
Undergo SBRT
Computed Tomography
Undergo CT and/or PET/CT
Positron Emission Tomography
Undergo PET/CT
Magnetic Resonance Imaging
Undergo MRI
Transurethral Resection of Bladder Tumor
Undergo TURBT
Cystoscopy
Undergo cystoscopy
Biospecimen Collection
Undergo collection of blood and urine samples
Questionnaire Administration
Ancillary studies
Locations (1)
Fred Hutch/University of Washington Cancer Consortium
Seattle, Washington, United States