This phase I trial studies the side effects and best dose of belinostat when given together
with tremelimumab and 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 tremelimumab and 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 tremelimumab, durvalumab, and belinostat may improve the body's ability to
I. To assess the recommended phase 2 dose of belinostat in combination with tremelimumab and
durvalumab in advanced solid tumors harboring ARID1A mutations with focus on urothelial
carcinoma. (Phase 1A) II. To assess the ongoing safety of belinostat in combination with
tremelimumab and durvalumab in patients with advanced solid tumors with ARID1A mutation with
focus on urothelial cancer. (Phase 1B)
I. To assess the efficacy of belinostat in combination with tremelimumab and durvalumab in
patients with advanced urothelial cancer with ARID1A mutation.
I. To assess the mechanism of action of belinostat in combination with tremelimumab and
II. To explore possible mechanisms of treatment resistance. III. 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.
If you are confirmed eligible after full screening, you will be required to understand and sign the informed consent if you decide to enroll in the study. Once enrolled you may be asked to make scheduled visits over a period of time.
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