Intravesical Nadofaragene Firadenovec With Neoadjuvant Chemotherapy and Durvalumab in Patients With Muscle Invasive Bladder Cancer (TRIFECTA)
University of Washington
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.
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 re…
Eligibility
- Age range
- 18+ years
- Sex
- All
- Healthy volunteers
- No
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 Oncolog…
Interventions
- BiologicalNadofaragene Firadenovec
Given intravesically
- BiologicalDurvalumab
Given IV
- DrugGemcitabine
Given IV
- DrugCisplatin
Given IV
- ProcedureRadical Cystectomy
Undergo RC
- ProcedureBiospecimen Collection
Undergo urine and blood sample collection
- ProcedureComputed Tomography
Undergo CT or PET/CT
Location
- Fred Hutch/University of Washington Cancer ConsortiumSeattle, Washington