A Phase I/II Study of Erlotinib and Romidepsin in Advanced Non-Small Cell Lung Cancer
- To characterize the toxicity and determine the maximum-tolerated dose (MTD) of
erlotinib hydrochloride plus romidepsin. (Phase I)
- To obtain preliminary data regarding efficacy, including response rate and
progression-free survival. (Phase II)
- To characterize the pharmacokinetic profile of romidepsin in combination with erlotinib
- To evaluate the impact of erlotinib hydrochloride on the biologic activity of
romidepsin by analyzing peripheral blood mononuclear cell (PBMC) histone acetylation
status and histone acetylase activity. (Exploratory)
- To evaluate the effect of romidepsin and erlotinib hydrochloride on components of the
EGFR-signaling pathway in skin biopsies, particularly downstream mediators such as
OUTLINE: This is a dose-escalation study of romidepsin followed by a phase II study.
Patients receive romidepsin IV on days 1, 8, and 15 and erlotinib hydrochloride orally (PO)
once daily beginning on day 3 of course 1 and on days 1-28 of all subsequent courses.
Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Patients undergo blood sample collection at baseline and periodically during study for
pharmacokinetic studies. Additional samples of peripheral blood mononuclear cells and skin
biopsies may be also collected for correlative studies.
After completion of study therapy, patients are followed up for 30 days.
PROJECTED ACCRUAL: A total of 39 patients (15 patients for phase I and 24 patients for phase
II) will be accrued for this study.
Masking: Open Label, Primary Purpose: Treatment
Toxicity of erlotinib hydrochloride plus romidepsin
David E. Gerber, MD
Simmons Cancer Center
|Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas||Dallas, Texas 75390|