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

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.

Conditions

• Muscle Invasive Bladder Carcinoma
• Stage III Bladder Cancer AJCC v8
• Stage IV Bladder Cancer AJCC v8

Interventions

PROCEDURE

Transurethral Resection of Bladder Tumor

Undergo TURBT

PROCEDURE

Cystoscopy

Undergo cystoscopy

PROCEDURE

Biospecimen Collection

Undergo collection of blood and urine samples

OTHER

Questionnaire Administration

Ancillary studies

PROCEDURE

Computed Tomography

Undergo CT and/or PET/CT

PROCEDURE

Positron Emission Tomography

Undergo PET/CT

PROCEDURE

Magnetic Resonance Imaging

Undergo MRI

DRUG

Fluorouracil

Given fluorouracil

DRUG

Mitomycin

Given mitomycin

PROCEDURE

Radical Cystectomy

Undergo radical cystectomy

PROCEDURE

Pelvic Lymphadenectomy

Undergo pelvic lymph node dissection

RADIATION

Stereotactic Body Radiation Therapy

Undergo SBRT

RADIATION

Intensity-Modulated Radiation Therapy

Undergo IMRT

RADIATION

Volume Modulated Arc Therapy

Undergo VMAT

DRUG

Cisplatin

Given IV

DRUG

Gemcitabine

Given IV

Sponsors & Collaborators

• Lopker Family Foundation

  collaborator UNKNOWN

• University of Washington

  lead OTHER

Principal Investigators

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

Study Design

Allocation

NA

Purpose

TREATMENT

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2026-06-01

Primary Completion

2029-12-31

Completion

2029-12-31

FDA Drug

Yes

Countries

• United States

Study Locations