Recruiting
Phase 1
Phase 2

Consolidative Treatment

Sponsor:

University of Washington

Code:

NCT07579195

Conditions

Muscle Invasive Bladder Carcinoma

Stage III Bladder Cancer AJCC v8

Stage IV Bladder Cancer AJCC v8

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Intensity-Modulated Radiation Therapy

Volume Modulated Arc Therapy

Radiosensitizing Agent

Radical Cystectomy

Pelvic Lymphadenectomy

Study Details

Brief summary:

This pilot feasibility 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.

Conditions

Muscle Invasive Bladder Carcinoma

Stage III Bladder Cancer AJCC v8

Stage IV Bladder Cancer AJCC v8

Study ID

NCT07579195

Start date

Aug 20, 2026

Status verified date

Jul, 2026

Completion date

Feb 1, 2030

Anticipated

Primary completion date

Feb 1, 2030

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Inclusion Criteria:

  • Age >= 18 at the time of screening
  • Ability to understand and willingness to sign a written informed consent document
  • Histopathologically confirmed cTxN1-3M0, cTxNxM1 or cT4bNxM0 muscle invasive bladder cancer at initial diagnosis
  • Achieved a radiographic complete response (CR) or partial response (PR), per Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1 criteria and at the determination of treating physicians) after 3-9 cycles of induction EV + pembro
  • If M1 after completion of EV + pembro, patients need to have =< 5 sites of metastasis and all sites of metastasis should be extracranial

  • Note: when counting the number of oligometastatic lesions, each lymph node lesion, whether pelvic or extrapelvic, is counted (for example, 2 distinct lymph nodes in the right external iliac basin count as 2 oligometastatic lesions; one extrapelvic and one pelvic node count as 2 oligometastatic lesions, etc). Five or fewer sites of metastasis applies after the completion of EV + pembro, not at initial diagnosis
  • Be a candidate for consolidative radiation therapy (RT) to the pelvis (if indicated) or cystectomy (if indicated), and all sites of metastasis are amenable to RT
  • Life expectancy > 6 months
  • Eastern Cooperative Oncology Group (ECOG) performance 0-2
  • Absolute neutrophil count (ANC) >= 1500 /mcL (within 180 days of trial registration)
  • Platelets >= 100,000/mcL (within 180 days of trial registration)
  • Hemoglobin > 9 g/dL (within 180 days of trial registration)
  • Creatinine =< 1.5 x upper limit of normal (ULN) OR >= 60 mL/min (within 180 days of trial registration)
  • Total bilirubin =< 1.5 ULN OR direct bilirubin =< ULN if total bilirubin > 1.5 x ULN (within 180 days of trial registration)
  • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 x ULN OR < 5 x ULN if patient has live metastasis (within 180 days of trial registration)
  • Albumin >= 2.5 g/dL (within 180 days of trial registration)
  • International normalized ratio (INR) or prothrombin time (PT) =< 1.5 x ULN unless on anticoagulation therapy, in which case PT or partial thromboplastin time (PTT) should be in the therapeutic range (within 180 days of trial registration)
  • PTT =< 1.5 x ULN unless on anticoagulation therapy, in which case PT or PTT should be in the therapeutic range (within 180 days of trial registration)
  • Participants of child-bearing potential must be willing to employ two highly effective and acceptable forms of contraception during, and for at least 90 days after the end of radiation therapy. Women of childbearing potential (WOCBP) must have a negative serum pregnancy test within 72 hours of treatment initiation
  • HIV-infected patients who are healthy and have a low risk of AIDS-related outcomes are included in this trial

Exclusion Criteria:

  • Prior radiation therapy with field overlapping with current proposed radiation field, precluding delivery of meaningful dose of radiation
  • Intracranial metastasis
  • Any small cell component, or predominant (> 50%) sarcomatoid or plasmacytoid histology
  • Other active malignancy or clinically relevant malignancy within past 2 years, per discussion with the principal investigator
  • Genetic conditions that increase sensitivity to radiation, such as Fanconi syndrome, ataxia telangiectasia, and Nijmegen breakage syndrome
  • Active human immunodeficiency virus (HIV) not adequately controlled, active hepatitis B (e.g., hepatitis B virus surface antigen \[HBsAg\] reactive) or hepatitis C (e.g., hepatitis C virus \[HCV\] ribonucleic acid \[RNA\] \[qualitative\] is detected), as determined by standard of care testing
  • Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial
  • Any other medical condition that may interfere with trial therapy delivery
  • Adults with impaired decision-making capacity, as determined by the treating physician

Study Design

Enrollment

12 participants

Anticipated

Intervention Model

Single group

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Local consolidative therapy

Following a complete re-TURBT, participants with residual bladder disease will receive either concurrent chemoradiation (IMRT/VMAT, 55 Gy in 20 fractions) to bladder +/- pelvic nodes or cystectomy, based on shared decision-making. For patients with a clinical complete response, bladder-directed consolidation is encouraged but optional. Patients with disease outside the true pelvis will receive metastasis-directed therapy (preferably SBRT) following primary chemoradiation to all site of metastasis. Participants then proceed to observation or maintenance pembrolizumab until progression, unacceptable toxicity, or clinical discretion. The study includes longitudinal imaging, cystoscopy, biospecimen collection, and quality-of-life assessments.

Interventions

Intensity-Modulated Radiation Therapy

Undergo IMRT

Volume Modulated Arc Therapy

Undergo VMAT

Radiosensitizing Agent

Given radiosensitizing chemotherapy

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 re-TURBT

Cystoscopy

Undergo cystoscopy

Biospecimen Collection

Undergo collection of blood and urine samples

Questionnaire Administration

Ancillary studies

Primary outcome measure

  • Completion rate of protocol-defined treatment (feasibility) [ Time Frame: 12 months since eligibility determination ]

Central Contacts and Locations

Central contacts

T. Martin Ma, MD, PhD

206-606-7318mma1@uw.edu

Locations

Fred Hutch/University of Washington Cancer Consortium

Recruiting

Seattle, Washington, United States, 98109

Contacts

T. Martin Ma, MD, PhD

206-606-7318mma1@uw.edu

Principal Investigator:

T. Martin Ma, MD, PhD

More Information

Sponsor

University of Washington

Last update posted

Aug 25, 2026

Last verified

Jul, 2026

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by University of Washington on 2026-08-25.