HERO Trial: Phase I Study Investigating Intravesical HDAC Inhibition to Improve Response to Immuno-Oncology Agents in Localized Bladder Cancer
In this study, we aim to evaluate the safety and efficacy of neoadjuvant combination using intravesical romidepsin and durvalumab in cisplatin-ineligible patients with muscle invasive bladder cancer (MIBC).
• Patients must have histologically confirmed MIBC (T2-T4a, N0, M0 per American Joint Commission on Cancer \[AJCC\]) pure or mixed histology urothelial carcinoma.
• Patients must be ineligible for cisplatin-based chemotherapy due to any of the following: Creatinine clearance (CrCl) \< 60 mL/min by the Cockcroft-Gault formula; Hearing impaired ≥ Grade 2 by CTCAE criteria; Neuropathy ≥ Grade 2 by CTCAE criteria; Heart failure NYHA ≥ III; ECOG ≥ 2.
• Patients must be medically fit for TURBT and radical cystectomy (RC
• Age ≥ 18 years
• Body weight \>30 kg
• Ability to understand and willingness to sign IRB-approved informed consent.
• Willing to provide tumor tissue, blood, and urine samples for research.
• ECOG performance status 0 or 1 (Karnofsky ≥80%).
• Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial.
• For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated.
• Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load.
• Participants must have adequate organ and marrow function as defined below: Hemoglobin ≥ 9.0 g/dL; Absolute neutrophil count (ANC) ≥ 1500/mcL; Platelet count ≥100,000/mcL; Serum bilirubin ≤1.5 x institutional upper limit of normal (ULN); total bilirubin must be \< 3 x ULN for patients with Gilberts syndrome; AST (SGOT)/ALT (SGPT) ≤2.5 x institutional upper limit of normal; Measured creatinine CL \>40 mL/min or Calculated creatinine CL\>40 mL/min by the Cockcroft-Gault formula or by 24-hour urine collection for determination of creatinine clearance.
• Evidence of post-menopausal status or negative urinary or serum pregnancy test for female pre-menopausal patients.
• Non-sterile males must be willing to use a highly effective method of birth control for the duration of the study and for ≥120 days after the last dose of durvalumab.
• Patient is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up.
• Patient must have a life expectancy of at least 12 weeks