Neoadjuvant Intravesical Nadofaragene Firadenovec With Gemcitabine, Cisplatin and Durvalumab for the Treatment of Muscle Invasive Bladder Cancer, TRIFECTA Trial (TRIFECTA)

March 11, 2026 updated by: University of Washington

Intravesical Nadofaragene Firadenovec With Neoadjuvant Chemotherapy and Durvalumab in Patients With Muscle Invasive Bladder Cancer (TRIFECTA)

This phase II trial tests the effect of intravesical nadofaragene firadenovec in combination with gemcitabine, cisplatin and durvalumab before (neoadjuvant) radical cystectomy (RC) in treating patients with muscle invasive bladder cancer. The combination of gemcitabine, cisplatin and durvalumab are already considered standard of care in the treatment of muscle invasive bladder cancer. This trial attempts to determine whether the addition of nadofaragene firadenovec to the current standard regiment is safe and can improve oncological outcomes for those with muscle invasive bladder cancer.

Nadofaragene firadenovec, a type of intravesical gene therapy, is a weakened adenovirus that carries a copy of the gene for interferon alfa-2b. This medication gets absorbed by the bladder and stimulates the bladder to naturally create interferon alfa-2b, which is thought to kill bladder cancer. Nadofaragene firadenovec is given in a solution that is placed directly into the bladder (intravesical) using a thin tube called a catheter. It is a medication that is already FDA approved for the treatment of non-muscle invasive bladder cancer. Gemcitabine is a chemotherapy drug that blocks the cells from making deoxyribonucleic acid and may kill tumor cells. Cisplatin is in a class of medications known as platinum-containing compounds. It works by killing, stopping or slowing the growth of tumor cells. Immunotherapy with monoclonal antibodies, such as durvalumab, may help the body's immune system attack the tumor, and may interfere with the ability of tumor cells to grow and spread.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed Description

OUTLINE:

Patients receive standard of care neoadjuvant therapies for muscle invasive bladder cancer including: durvalumab intravenously (IV) over 60 minutes on day 1, gemcitabine IV over 30 minutes on days 1 and 8, and cisplatin IV on day 1 or days 1 and 8 of each cycle. In addition, patients also receive nadofaragene firadenovec intravesically on day 1 of cycles 1 and 4. Cycles repeat every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Starting 4-8 weeks after treatment, patients undergo RC per standard clinical care. Following RC, patients may receive durvalumab at the discretion of the clinician. Additionally, patients undergo urine and blood sample collection and computed tomography (CT), magnetic resonance imaging (MRI) or positron emission tomography (PET)/CT throughout the study.

After completion of study treatment, patients are followed for up to 30 days post-cystectomy to monitor for adverse events.

Study Type

Interventional

Enrollment (Estimated)

33

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: Jonathan Wright, MD
  • Phone Number: 206-598-4294
  • Email: jlwright@uw.edu

Study Locations

  • United States
    • Washington
      • Seattle, Washington, United States, 98109
        • Fred Hutch/University of Washington Cancer Consortium
        • Principal Investigator:
          • Jonathan Wright, MD
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Age ≥ 18 years at the time of screening
  • Ability to understand and willingness to sign the written informed consent document
  • Patients with confirmed muscle-invasive urothelial carcinoma of the bladder (cT2-4a, N0-1, M0 or cT1, N1, M0), who are planning to undergo RC
  • Pure urothelial or mixed histologic subtypes are allowed if urothelial is the primary histology (regardless of the % of conventional urothelial histology)
  • Eligible to receive neoadjuvant cisplatin/gemcitabine and durvalumab per the patient's medical oncologist's discretion
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-1
  • Hemoglobin count ≥ 9 gm/dL
  • Absolute neutrophil count of ≥ 1500 cells/uL
  • Platelet count of ≥ 100,000/uL
  • Alanine and aspartate aminotransferase levels ≤ 2.5 x upper limit of normal (ULN)
  • Total bilirubin ≤ 1.5 x ULN (≤ 2.5 x ULN for Gilbert syndrome)
  • Creatinine clearance or estimated glomerular filtration rate (GFR) ≥ 40ml/min (using Chronic Kidney Disease Epidemiology Collaboration Formula [CKD-EPI] 2021 equation)
  • For patients with evidence of, or history of HIV, chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infection, the viral load must be undetectable, or the infection must have been treated and cured. Patients are not allowed to be on immunosuppressive agents for HIV, HBV or HCV. Routine testing for HIV, HBV and HCV is not required for patients without such history unless clinically indicated
  • Individuals with a prior malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are allowed to enroll

Exclusion Criteria:

  • cT4b, N2-3, or M1 stage at time of screening
  • Any known concurrent clinically relevant malignancies
  • Prior systemic therapy for muscle-invasive bladder carcinoma (MIBC) (prior intravenous pembrolizumab for non-muscle invasive bladder carcinoma [NMIBC] is allowed)
  • Current or prior use of systemic immunosuppressive medication within 14 days before first dose of investigational product. The following are allowed (not systemic route): intranasal, inhaled, intra-articular, topical steroids, local steroid injections
  • Pure non-urothelial histology subtype/variant or any neuroendocrine (small or large cell) component
  • Prior treatment with adenovirus-based drugs
  • Known hypersensitivity or allergy to any components of rAd-interferon (IFN)a/Syn3
  • Currently receiving other investigational agent
  • Pregnant or lactating women

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Treatment (durvalumab, chemotherapy, nadofaragene firadenovec)
Patients receive durvalumab IV over 60 minutes on day 1, gemcitabine IV over 30 minutes on days 1 and 8, and cisplatin IV on day 1 or days 1 and 8 of each cycle. Patients also receive nadofaragene firadenovec intravesically on day 1 of cycles 1 and 4. Cycles repeat every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Starting 4-8 weeks after treatment, patients undergo RC per standard clinical care. Following RC, patients may receive durvalumab at the discretion of the clinician. Additionally, patients undergo urine and blood sample collection and CT, MRI or PET/CT throughout the study.
Procedure: Magnetic Resonance Imaging
Undergo MRI
Other Names:
  • MRI
Drug: Cisplatin
Given IV
Other Names:
  • Cisplatinum
  • Platinol
Drug: Gemcitabine
Given IV
Biological: Durvalumab
Given IV
Other Names:
  • Imfinzi
  • MEDI 4736
  • Immunoglobulin G1
  • Anti-(Human Protein B7-H1) (Human Monoclonal MEDI4736 Heavy Chain)
  • Disulfide with Human Monoclonal MEDI4736 Kappa-chain
Procedure: Positron Emission Tomography
Undergo PET/CT
Other Names:
  • PET
  • PET Scan
Procedure: Computed Tomography
Undergo CT or PET/CT
Other Names:
  • CT
  • CAT Scan
  • CT Scan
Procedure: Biospecimen Collection
Undergo urine and blood sample collection
Other Names:
  • Biological Sample Collection
Biological: Nadofaragene Firadenovec
Given intravesically
Other Names:
  • Adstiladrin
  • Instiladrin
  • Recombinant Adenovirus-Interferon SCH 721015
  • Recombinant Adenovirus-Interferon With Syn3
  • Recombinant Adenovirus-Interferon/Syn3
  • SCH 721015
Procedure: Radical Cystectomy
Undergo RC
Other Names:
  • RC

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Pathological complete response (pCR) on radical cystectomy (RC) specimen
Time Frame: At time of radical cystectomy (RC), approximately 4-8 weeks following completion of neoadjuvant systemic therapies
Will be defined as the proportion of participants achieving ypT0N0. Will employ Simon's optimal two-stage design (Simon, 1989) to test the null hypothesis that the true pCR rate is 33.8% versus the alternative hypothesis of 56%. The observed pCR rate will be reported with an exact 95% confidence interval using the Clopper-Pearson method.
At time of radical cystectomy (RC), approximately 4-8 weeks following completion of neoadjuvant systemic therapies
Downstaging (≤ ypT1N0) on RC specimen
Time Frame: At time of radical cystectomy (RC), approximately 4-8 weeks following completion of neoadjuvant systemic therapies
At time of radical cystectomy (RC), approximately 4-8 weeks following completion of neoadjuvant systemic therapies

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Proportion of patients who undergo RC
Time Frame: Within 10 weeks from last neoadjuvant therapy dose
Will be defined as the number of patients who ultimately receive RC divided by the total number of patients that receive at least one administration of neoadjuvant therapy.
Within 10 weeks from last neoadjuvant therapy dose
Incidence of grade 3 or higher treatment-related adverse events (AE)
Time Frame: From initiation of neoadjuvant systemic therapies (day 1 of cycle 1; 4 cycles total; each cycle is 21 days), through 30 days post-RC (RC occurs approximately 4-8 weeks after completion of neoadjuvant systemic therapies)
Will be graded by provider-scored toxicity via the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Will be summarized descriptively, including the number and proportion of patients experiencing at least one grade ≥ 3 AE, and the type, severity, and relatedness of all treatment-related AEs, attributed by agent.
From initiation of neoadjuvant systemic therapies (day 1 of cycle 1; 4 cycles total; each cycle is 21 days), through 30 days post-RC (RC occurs approximately 4-8 weeks after completion of neoadjuvant systemic therapies)
Incidence of AEs
Time Frame: From initiation of neoadjuvant systemic therapies (day 1 of cycle 1; 4 cycles total; each cycle is 21 days), through 30 days post-RC (RC occurs approximately 4-8 weeks after completion of neoadjuvant systemic therapies)
Will be summarized by maximum CTCAE grade and relatedness to the treatment.
From initiation of neoadjuvant systemic therapies (day 1 of cycle 1; 4 cycles total; each cycle is 21 days), through 30 days post-RC (RC occurs approximately 4-8 weeks after completion of neoadjuvant systemic therapies)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Washington

Collaborators

Ferring Pharmaceuticals

Investigators

  • Principal Investigator: Jonathan Wright, MD, Fred Hutch/University of Washington Cancer Consortium

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

June 1, 2026

Primary Completion (Estimated)

January 1, 2027

Study Completion (Estimated)

February 1, 2027

Study Registration Dates

First Submitted

January 6, 2026

First Submitted That Met QC Criteria

January 8, 2026

First Posted (Actual)

January 12, 2026

Study Record Updates

Last Update Posted (Actual)

March 13, 2026

Last Update Submitted That Met QC Criteria

March 11, 2026

Last Verified

January 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • RG1126027
  • NCI-2025-09407 (Registry Identifier: CTRP (Clinical Trial Reporting Program))

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Stage IIIA Bladder Cancer AJCC v8

Clinical Trials on Magnetic Resonance Imaging

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Ecuador

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe