AzTrials
AzTrials

Muscle Invasive Bladder CarcinomaPhase 1/2NCT07579195

Consolidative Therapy After EV + Pembrolizumab in Muscle Invasive Bladder Cancer, REINFORCE Trial

A Phase 1/2 study testing Intensity-Modulated Radiation Therapy, Volume Modulated Arc Therapy and Radiosensitizing Agent in people with Muscle Invasive Bladder Carcinoma and Stage III Bladder Cancer AJCC v8, run by University of Washington at 1 site in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial 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… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Intensity-Modulated Radiation Therapy, Volume Modulated Arc Therapy and Radiosensitizing Agent
Type of treatment
Surgery or procedure
Could I receive a placebo?
No, everyone receives an active treatment
How many people
12 participants
Where
1 siteUnited States
Study dates
20 Aug 2026to 1 Feb 2030
Phase
Phase 1/2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
Show all 20Show fewer
  • 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

Who cannot join

  • 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
Show all 9Show fewer
  • 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

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

T. Martin Ma, MD, PhD contact

206-606-7318

mma1@uw.edu

United States1 site, 1 recruiting

  • Fred Hutch/University of Washington Cancer Consortium

    Seattle, Washington, 98109

    T. Martin Ma, MD, PhD, 206-606-7318, mma1@uw.edu

    T. Martin Ma, MD, PhD

    Recruiting

Other trials in United States

About this study

Official title: Consolidative Radiation Therapy or Cystectomy After Initial Favorable Response Succeeding Enfortumab Vedotin Plus Pembrolizumab (REINFORCE)--- A Pilot Feasibility Trial

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.

Read the detailed description

OUTLINE: This is a single arm, phase I/II study of consolidative therapy after initial favorable response after enfortumab vedotin and pembrolizumab. For patients with a complete response (cCR) in the bladder, local consolidative therapy (radiation or cystectomy) as described below is encouraged but not required. They will participate in a discussion with the treating physician regarding the limitations of a cCR. For patients with residual tumor in the bladder (not achieving a cCR), local consolidative therapy, either in the form of radiation or cystectomy will be delivered, per shared decision-making with their treating physician. Concurrent radiosensitizing chemotherapy will be delivered with radiation therapy to the bladder, whenever feasible. Regardless of the disease status in the bladder, patients with residual disease outside the bladder receive metastasis-directed therapy (MDT), as described below.

RADIATION TO THE BLADDER/PELVIS: Patients undergo radiation therapy to the bladder with intensive-modulated radiation therapy (IMRT)/volume modulated arc therapy (VMAT) daily for a total of 20 fractions over 4 weeks. Patients may undergo pelvic lymph node-directed radiation therapy with simultaneous integrated boost to the bladder daily for 20 fractions, if indicated. Patients also receive radiosensitizing chemotherapy, per physician discretion and according to standard of care, concurrently with radiation therapy.

CYSTECTOMY: Patients undergo radical cystectomy with pelvic lymph node dissection on study.

MDT: Patients undergo metastasis-directed radiation therapy with stereotactic body radiation therapy (SBRT) for 3-5 fractions, as determined by the treating physician.

Patients also undergo computed tomography (CT), magnetic resonance imaging (MRI), and/or positron emission tomography (PET)/CT and collection of blood and urine samples throughout the trial, undergo re-transurethral resection of bladder tumor (re-TURBT) on study, and undergo cystoscopy during follow-up.

After completion of study treatment, patients are followed up every 3 months for up to 12 months (1 year) on study.

Being tested
Intensity-Modulated Radiation Therapy, Volume Modulated Arc Therapy, Radiosensitizing Agent, Radical Cystectomy, Pelvic Lymphadenectomy
Medical subject headings
Urinary Bladder Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Intensity-Modulated Radiation TherapyRadiation

    Also called IMRT, Intensity modulated radiation therapy (procedure), Intensity Modulated RT

    Undergo IMRT

  • Volume Modulated Arc TherapyRadiation

    Also called VMAT, Volumetric Modulated Arc Therapy (procedure)

    Undergo VMAT

  • Radiosensitizing AgentDrug

    Also called Radiation Sensitizers, Radiation-Sensitizing Agents, Radiation-Sensitizing Drugs, radiosensitizer

    Given radiosensitizing chemotherapy

  • Radical CystectomyProcedure or surgery

    Undergo radical cystectomy

  • Pelvic LymphadenectomyProcedure or surgery

    Also called Excision Pelvic Lymph Nodes, Pelvic Lymph Node Dissection

    Undergo pelvic lymph node dissection

  • Stereotactic Body Radiation TherapyRadiation

    Also called SBRT, SABR, Stereotactic Ablative Body Radiation Therapy

    Undergo SBRT

  • Computed TomographyProcedure or surgery

    Also called CT, CT Scan, CAT Scan

    Undergo CT and/or PET/CT

  • Positron Emission TomographyProcedure or surgery

    Also called PET, PET scan

    Undergo PET/CT

  • Magnetic Resonance ImagingProcedure or surgery

    Also called MRI

    Undergo MRI

  • Transurethral Resection of Bladder TumorProcedure or surgery

    Also called Transurethral resection (TURBT), TURBT

    Undergo re-TURBT

  • CystoscopyProcedure or surgery

    Also called CS

    Undergo cystoscopy

  • Biospecimen CollectionProcedure or surgery

    Also called Biological Sample Collection

    Undergo collection of blood and urine samples

  • Questionnaire AdministrationOther

    Ancillary studies

Study groups in NCT07579195
Study groupRoleWhat they receive
Local consolidative therapyExperimentalFollowing 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.
Receives: Radiation: Intensity-Modulated Radiation Therapy; Radiation: Volume Modulated Arc Therapy; Drug: Radiosensitizing Agent; Procedure: Radical Cystectomy; Procedure: Pelvic Lymphadenectomy; Radiation: Stereotactic Body Radiation Therapy; Procedure: Computed Tomography; Procedure: Positron Emission Tomography; Procedure: Magnetic Resonance Imaging; Procedure: Transurethral Resection of Bladder Tumor; Procedure: Cystoscopy; Procedure: Biospecimen Collection; Other: Questionnaire Administration

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Completion rate of protocol-defined treatment (feasibility)

    Feasibility will be assessed through the completion rate of protocol-defined treatment. Primary endpoint is met if the completion rate of protocol-defined treatment is > 70%. Descriptive statistics will be provided.

    Measured: 12 months since eligibility determination

Secondary outcomes (6)

  1. Progression-free survival

    The Kaplan-Meier method will be used.

    Measured: From date of enfortumab vedotin (EV) + pembrolizumab start to date of first documentation of progression assessed by local review, or death due to any cause, assessed up to 12 months

  2. Incidence of treatment-related grade 3 or higher adverse events

    Safety of consolidative radiation therapy will be assessed by the incidence of treatment-related grade 3 or higher toxicities per Common Terminology Criteria for Adverse Events version 6 that is possibly, probably, or definitely related to radiation treatment or chemoradiation therapy. Descriptive statistics will be provided.

    Measured: Up to 12 months after the completion of consolidative therapy

  3. Change in patient-reported quality of life

    Changes in patient-reported quality of life will be measured by the Functional Assessment of Cancer Therapy-Bladder (FACT-Bl) assessment. Will measure change in total FACT-Bl score from baseline to each follow-up assessment as well as changes in individual domain subscale scores (physical, social/family, emotional, functional well-being, and bladder-specific concerns). Each question is scored 0-4 and higher score indicates better quality of life (for negatively worded items [e.g., symptoms, distress], scores are reversed). Clinically meaningful deterioration or improvement will be defined using established minimally important difference thresholds for FACT-Bl.

    Measured: From baseline to each follow-up assessment (every 3 months up to 12 months after completion of consolidative therapy)

  4. Time to progression in the bladder (local control)

    The Kaplan-Meier method will be used.

    Measured: 12 months since the start of EV + pembrolizumab

  5. Time to progression in the pelvis (pelvic control)

    The Kaplan-Meier method will be used.

    Measured: 12 months since the start of EV + pembrolizumab

  6. Overall survival

    The Kaplan-Meier method will be used.

    Measured: From first date of EV + pembrolizumab to death from any cause, assessed up to 12 months since the start of EV + pembrolizumab

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted12 May 2026
  2. Study start20 Aug 2026
  3. Primary completion1 Feb 2030 (estimated)
  4. Study completion1 Feb 2030 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
12 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07579195
Sponsor's protocol ID
RG1126354
Other IDs
NCI-2026-02920, FHIRB0021260
Status last verified
Jul 2026
First submitted
4 May 2026
Last updated
25 Aug 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Intensity-Modulated Radiation Therapy, Volume Modulated Arc Therapy and Radiosensitizing Agent in people with Muscle Invasive Bladder Carcinoma and Stage III Bladder Cancer AJCC v8, run by University of Washington at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 20 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 25 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact T. Martin Ma, MD, PhD (206-606-7318, mma1@uw.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Completion rate of protocol-defined treatment (feasibility) (time frame: 12 months since eligibility determination). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT07579195.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Aug 2026.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in