NCT07332351

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

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

• Status: Not Yet Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 33 (estimated)
• Sponsor: University of Washington · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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. 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.

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.

Conditions

• Muscle Invasive Bladder Urothelial Carcinoma
• Stage II Bladder Cancer AJCC v8
• Stage IIIA Bladder Cancer AJCC v8

Interventions

Type	Name	Description
BIOLOGICAL	Nadofaragene Firadenovec	Given intravesically
BIOLOGICAL	Durvalumab	Given IV
DRUG	Gemcitabine	Given IV
DRUG	Cisplatin	Given IV
PROCEDURE	Radical Cystectomy	Undergo RC
PROCEDURE	Biospecimen Collection	Undergo urine and blood sample collection
PROCEDURE	Computed Tomography	Undergo CT or PET/CT
PROCEDURE	Positron Emission Tomography	Undergo PET/CT
PROCEDURE	Magnetic Resonance Imaging	Undergo MRI

Timeline

• Start date: 2026-06-01
• Primary completion: 2027-01-01
• Completion: 2027-02-01
• First posted: 2026-01-12
• Last updated: 2026-03-13

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study