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Muscle Invasive Bladder Urothelial CarcinomaPhase 2TRIFECTANCT07332351

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

A Phase 2 study testing Nadofaragene Firadenovec, Durvalumab and Gemcitabine in people with Muscle Invasive Bladder Urothelial Carcinoma and Stage II Bladder Cancer AJCC v8, run by University of Washington at 1 site in United States.

Not yet recruiting

Opening soon. The study is approved but enrolment has not started yet. Sites may already take enquiries.

Sites and contacts
Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Nadofaragene Firadenovec, Durvalumab and Gemcitabine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
33 participants
Where
1 siteUnited States
Study dates
1 Dec 2026to 1 Feb 2027
Phase
Phase 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 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
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  • 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

Who cannot join

  • 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
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  • Known hypersensitivity or allergy to any components of rAd-interferon (IFN)a/Syn3
  • Currently receiving other investigational agent
  • Pregnant or lactating women

Trial locations and contacts

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

Jonathan Wright, MD contact

206-598-4294

jlwright@uw.edu

United States1 site

  • Fred Hutch/University of Washington Cancer Consortium

    Seattle, Washington, 98109

    Jonathan Wright, MD, 206-598-4294, jlwright@uw.edu

    Jonathan Wright, MD

Other trials in United States

About this study

Official title: 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.

Read the 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.

Being tested
Nadofaragene Firadenovec, Durvalumab, Gemcitabine, Cisplatin, Radical Cystectomy
Keywords
Urinary Bladder
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.

  • Nadofaragene FiradenovecBiological

    Also called Adstiladrin, Instiladrin, Recombinant Adenovirus-Interferon SCH 721015, Recombinant Adenovirus-Interferon With Syn3

    Given intravesically

  • DurvalumabBiological

    Also called Imfinzi, Immunoglobulin G1, Anti-(Human Protein B7-H1) (Human Monoclonal MEDI4736 Heavy Chain), Disulfide with Human Monoclonal MEDI4736 Kappa-chain

    Given IV

  • GemcitabineDrug

    Given IV

  • CisplatinDrug

    Also called Cisplatinum, Platinol

    Given IV

  • Radical CystectomyProcedure or surgery

    Also called RC

    Undergo RC

  • Biospecimen CollectionProcedure or surgery

    Also called Biological Sample Collection

    Undergo urine and blood sample collection

  • Computed TomographyProcedure or surgery

    Also called CT, CT Scan, CAT Scan

    Undergo CT 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

Study groups in NCT07332351
Study groupRoleWhat they receive
Treatment (durvalumab, chemotherapy, nadofaragene firadenovec)ExperimentalPatients 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.
Receives: Biological: Nadofaragene Firadenovec; Biological: Durvalumab; Drug: Gemcitabine; Drug: Cisplatin; Procedure: Radical Cystectomy; Procedure: Biospecimen Collection; Procedure: Computed Tomography; Procedure: Positron Emission Tomography; Procedure: Magnetic Resonance Imaging

What is being measured

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

  1. Pathological complete response (pCR) on radical cystectomy (RC) specimen

    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.

    Measured: At time of radical cystectomy (RC), approximately 4-8 weeks following completion of neoadjuvant systemic therapies

  2. Downstaging (≤ ypT1N0) on RC specimen

    Measured: At time of radical cystectomy (RC), approximately 4-8 weeks following completion of neoadjuvant systemic therapies

Secondary outcomes (3)

  1. Proportion of patients who undergo RC

    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.

    Measured: Within 10 weeks from last neoadjuvant therapy dose

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

    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.

    Measured: 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)

  3. Incidence of AEs

    Will be summarized by maximum CTCAE grade and relatedness to the treatment.

    Measured: 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)

Timeline

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

  1. First posted12 Jan 2026
  2. Study start1 Dec 2026 (estimated)
  3. Primary completion1 Jan 2027 (estimated)
  4. Study completion1 Feb 2027 (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 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
33 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07332351
Sponsor's protocol ID
RG1126027
Other IDs
NCI-2025-09407
Acronym
TRIFECTA
Status last verified
Jan 2026
First submitted
6 Jan 2026
Last updated
26 Oct 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 2 study testing Nadofaragene Firadenovec, Durvalumab and Gemcitabine in people with Muscle Invasive Bladder Urothelial Carcinoma and Stage II 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 14 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: opening soon, as of the sponsor's last update on 26 Oct 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 phase mean?

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 Jonathan Wright, MD (206-598-4294, jlwright@uw.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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). The study lists 2 primary outcomes in all. 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 NCT07332351.

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 26 Oct 2026.

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