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

21. august 2026 oppdatert av: University of Washington

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.

Studieoversikt

Status

Rekruttering

Forhold

Intervensjon / Behandling

Detaljert beskrivelse

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.

Studietype

Intervensjonell

Registrering (Antatt)

12

Fase

  • Fase 2
  • Fase 1

Kontakter og plasseringer

Denne delen inneholder kontaktinformasjon for de som utfører studien, og informasjon om hvor denne studien blir utført.

Studiekontakt

  • Navn: T. Martin Ma, MD, PhD
  • Telefonnummer: 206-606-7318
  • E-post: mma1@uw.edu

Studiesteder

  • Forente stater
    • Washington
      • Seattle, Washington, Forente stater, 98109
        • Rekruttering
        • Fred Hutch/University of Washington Cancer Consortium
        • Ta kontakt med:
          • T. Martin Ma, MD, PhD
          • Telefonnummer: 206-606-7318
          • E-post: mma1@uw.edu
        • Hovedetterforsker:
          • T. Martin Ma, MD, PhD

Deltakelseskriterier

Forskere ser etter personer som passer til en bestemt beskrivelse, kalt kvalifikasjonskriterier. Noen eksempler på disse kriteriene er en persons generelle helsetilstand eller tidligere behandlinger.

Kvalifikasjonskriterier

Alder som er kvalifisert for studier

  • Voksen
  • Eldre voksen

Tar imot friske frivillige

Nei

Beskrivelse

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

Studieplan

Denne delen gir detaljer om studieplanen, inkludert hvordan studien er utformet og hva studien måler.

Hvordan er studiet utformet?

Designdetaljer

  • Primært formål: Behandling
  • Tildeling: N/A
  • Intervensjonsmodell: Enkeltgruppeoppdrag
  • Masking: Ingen (Open Label)

Våpen og intervensjoner

Deltakergruppe / Arm
Intervensjon / Behandling
Eksperimentell: 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.
Annen: Spørreskjemaadministrasjon
Hjelpestudier
Fremgangsmåte: Magnetisk resonansavbildning
Gjennomgå MR
Andre navn:
  • MR
Stråling: Intensitetsmodulert strålebehandling
Gjennomgå IMRT
Andre navn:
  • IMRT
  • Intensitetsmodulert RT
  • Intensitetsmodulert strålebehandling (prosedyre)
Stråling: Stereotaktisk kroppsstrålebehandling
Gjennomgå SBRT
Andre navn:
  • SBRT
  • SABR
  • Stereotaktisk ablativ kroppsstrålebehandling
Fremgangsmåte: Positron-utslippstomografi
Gjennomgå PET/CT
Andre navn:
  • KJÆLEDYR
  • PET-skanning
Fremgangsmåte: Radikal cystektomi
Gjennomgå radikal cystektomi
Fremgangsmåte: Cystoskopi
Gjennomgå cystoskopi
Andre navn:
  • CS
Fremgangsmåte: Computertomografi
Gjennomgå CT og/eller PET/CT
Andre navn:
  • CT
  • CAT-skanning
  • CT skann
Stråling: Volummodulert bueterapi
Gjennomgå VMAT
Andre navn:
  • VMAT
  • Volumetrisk modulert bueterapi (prosedyre)
Fremgangsmåte: Bioprøvesamling
Gjennomgå innsamling av blod- og urinprøver
Andre navn:
  • Biologisk prøvesamling
Fremgangsmåte: Bekkenlymfadenektomi
Gjennomgå bekkenlymfeknute -disseksjon
Andre navn:
  • Eksisjon bekkenlymfeknuter
  • Bekkenlymfeknutedisseksjon
Legemiddel: Radiosensitizing Agent
Given radiosensitizing chemotherapy
Andre navn:
  • Radiation Sensitizers
  • Radiation-Sensitizing Agents
  • Radiation-Sensitizing Drugs
  • radiosensitizer
  • Radiosensitizers
  • Radiosensitizing Drugs
Fremgangsmåte: Transurethral Resection of Bladder Tumor
Undergo re-TURBT
Andre navn:
  • Transuretral reseksjon (TURBT)
  • TURBT

Hva måler studien?

Primære resultatmål

Resultatmål
Tiltaksbeskrivelse
Tidsramme
Completion rate of protocol-defined treatment (feasibility)
Tidsramme: 12 months since eligibility determination
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.
12 months since eligibility determination

Sekundære resultatmål

Resultatmål
Tiltaksbeskrivelse
Tidsramme
Progression-free survival
Tidsramme: 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
The Kaplan-Meier method will be used.
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
Incidence of treatment-related grade 3 or higher adverse events
Tidsramme: Up to 12 months after the completion of consolidative therapy
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.
Up to 12 months after the completion of consolidative therapy
Change in patient-reported quality of life
Tidsramme: From baseline to each follow-up assessment (every 3 months up to 12 months after completion of consolidative therapy)
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.
From baseline to each follow-up assessment (every 3 months up to 12 months after completion of consolidative therapy)
Time to progression in the bladder (local control)
Tidsramme: 12 months since the start of EV + pembrolizumab
The Kaplan-Meier method will be used.
12 months since the start of EV + pembrolizumab
Time to progression in the pelvis (pelvic control)
Tidsramme: 12 months since the start of EV + pembrolizumab
The Kaplan-Meier method will be used.
12 months since the start of EV + pembrolizumab
Overall survival
Tidsramme: From first date of EV + pembrolizumab to death from any cause, assessed up to 12 months since the start of EV + pembrolizumab
The Kaplan-Meier method will be used.
From first date of EV + pembrolizumab to death from any cause, assessed up to 12 months since the start of EV + pembrolizumab

Samarbeidspartnere og etterforskere

Det er her du vil finne personer og organisasjoner som er involvert i denne studien.

Sponsor

University of Washington

Samarbeidspartnere

Lopker Family Foundation

Etterforskere

  • Hovedetterforsker: T. Martin Ma, MD, PhD, Fred Hutch/University of Washington Cancer Consortium

Studierekorddatoer

Disse datoene sporer fremdriften for innsending av studieposter og sammendragsresultater til ClinicalTrials.gov. Studieposter og rapporterte resultater gjennomgås av National Library of Medicine (NLM) for å sikre at de oppfyller spesifikke kvalitetskontrollstandarder før de legges ut på det offentlige nettstedet.

Studer hoveddatoer

Studiestart (Faktiske)

20. august 2026

Primær fullføring (Antatt)

1. februar 2030

Studiet fullført (Antatt)

1. februar 2030

Datoer for studieregistrering

Først innsendt

4. mai 2026

Først innsendt som oppfylte QC-kriteriene

4. mai 2026

Først lagt ut (Faktiske)

12. mai 2026

Oppdateringer av studieposter

Sist oppdatering lagt ut (Faktiske)

25. august 2026

Siste oppdatering sendt inn som oppfylte QC-kriteriene

21. august 2026

Sist bekreftet

1. juli 2026

Mer informasjon

Begreper knyttet til denne studien

Ytterligere relevante MeSH-vilkår

Andre studie-ID-numre

  • RG1126354
  • NCI-2026-02920 (Registeridentifikator: CTRP (Clinical Trial Reporting Program))
  • FHIRB0021260 (Annen identifikator: Fred Hutch/University of Washington Cancer Consortium)

Plan for individuelle deltakerdata (IPD)

Planlegger du å dele individuelle deltakerdata (IPD)?

NEI

Legemiddel- og utstyrsinformasjon, studiedokumenter

Studerer et amerikansk FDA-regulert medikamentprodukt

Ja

Studerer et amerikansk FDA-regulert enhetsprodukt

Nei

Denne informasjonen ble hentet direkte fra nettstedet clinicaltrials.gov uten noen endringer. Hvis du har noen forespørsler om å endre, fjerne eller oppdatere studiedetaljene dine, vennligst kontakt register@clinicaltrials.gov. Så snart en endring er implementert på clinicaltrials.gov, vil denne også bli oppdatert automatisk på nettstedet vårt. .

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