NCT05154994

Tremelimumab + Durvalumab(MEDI4736)+ Belinostat in Urothelial Carcinoma

RESOLVE : A Phase I Trial of Tremelimumab + Durvalumab(MEDI4736)+ Belinostat in Urothelial Carcinoma

• Status: Active Not Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 9 (estimated)
• Sponsor: University of Utah · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This phase I trial studies the side effects and best dose of belinostat when given together with durvalumab in treating patients with urothelial cancer that has spread to other places in the body (metastatic) or cannot be removed by surgery (unresectable) and has spread to nearby tissue or lymph nodes (locally advanced). Immunotherapy with monoclonal antibodies, such as durvalumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Belinostat is a potential anti-cancer drug, known as a histone deacetylase (HDAC) inhibitor, which means that belinostat stops the activity of HDAC enzymes (an enzyme is a protein that in small amounts can speed up a biological reaction). HDAC enzymes play an important role in cell growth and cell death. Giving durvalumab and belinostat may improve the body's ability to fight cancer.

Detailed description

PRIMARY OBJECTIVES: I. To assess the recommended phase 2 dose of belinostat in combination with tremelimumab and durvalumab or belinostat in combination with durvalumab alone in advanced urothelial carcinoma. (Phase 1A) II. To assess the ongoing safety of belinostat in combination with durvalumab in patients with advanced urothelial carcinoma. (Phase 1B) SECONDARY OBJECTIVES: I. To assess the efficacy of belinostat in combination with tremelimumab and durvalumab or belinostat in combination with durvalumab in patients with advanced urothelial carcinoma. EXPLORATORY OBJECTIVES: I. To assess the mechanism of action of belinostat in combination with tremelimumab and durvalumab or belinostat in combination with durvalumab. II. To explore possible mechanisms of treatment resistance. III. Determine the feasibility of establishing patient-derived xenografts from tumor cells collected from enrolled subjects at baseline, and progression to better explore mechanisms of response and resistance. IIII. To explore possible biomarkers predictive of treatment benefit. OUTLINE: This is a dose-escalation study of belinostat. Patients receive durvalumab intravenously (IV) over 30 minutes on day 1. Patients also receive tremelimumab IV over 60 minutes on day 1 of cycle 1. Beginning cycle 2, patients receive belinostat IV over 30 minutes on days 1-5. Treatment repeats every 21 days for 7 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive durvalumab IV over 30 minutes on day 1. Treatment repeats every 28 days for up to 24 cycles in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 3 months for 1 year and then every 6 months for 2 years.

Conditions

• Infiltrating Urothelial Carcinoma, Sarcomatoid Variant
• Locally Advanced Urothelial Carcinoma
• Metastatic Urothelial Carcinoma
• Unresectable Urothelial Carcinoma

Interventions

Type	Name	Description
DRUG	Belinostat	Given IV
BIOLOGICAL	Durvalumab	Given IV

Timeline

• Start date: 2022-01-14
• Primary completion: 2026-04-01
• Completion: 2027-11-30
• First posted: 2021-12-13
• Last updated: 2026-01-27

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study