A Phase I Study of Belinostat in Combination With Cisplatin and Etoposide in Adults With a Focus on Small Cell Lung Cancer and Other Cancers of Neuroendocrine Origin
- The histone deacetylase (HDAC) inhibitors are a novel class of anticancer agent. These
agents lead to the increased acetylation of both histone and non-histone proteins,
which leads to rapid cell death in many tumor models. It is thought that the cell death
observed with this class of agents may be mediated, in part, through the selective
acetylation of histone proteins resulting in increased expression of specific genes.
- For solid tumors in general, cell death in preclinical models has not translated to
activity in patients. For this reason, studies increasingly have combined chemotherapy
with HDAC inhibitors to achieve additive and potentially synergistic effects on cancer
- This protocol will study a continuous infusion of the HDAC inhibitor belinostat in
combination with cisplatin and etoposide for patients with advanced cancer.
- To determine a safe and tolerable phase 2 dose for the combination of belinostat with
cisplatin and etoposide.
- Evaluate molecular markers of HDAC inhibition.
- The protocol will be open to all patients with recurrent or advanced cancer (small-cell
lung cancer and other advanced cancers) for whom standard therapy offers no curative
- Age greater than or equal to 18 years
- ECOG Performance Status 0-2
-The study will begin with belinostat 400 mg/m (2)/24h administered by continuous IV
infusion on days 1 and 2, cisplatin at 60 mg/m (2) IV on day 2, and etoposide at 80 mg/m
(2) IV daily times 3 on days 2 - 4. Dose escalation of belinostat will follow according to
traditional 3 patient cohorts.
Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
To determine a safe and tolerable phase 2 dose for the combination of belinostat with cisplatin and etoposide.
Susan E Bates, M.D.
National Cancer Institute (NCI)
United States: Federal Government
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