Romidepsin and Erlotinib Hydrochloride in Treating Patients With Stage III or Stage IV Non-Small Cell Lung Cancer

Phase 1

Completed

Conditions: Metastatic Cancer
Lung Cancer

Interventions: Combination Product: (Erlotinib plus Romidepsin (8mg/m^2)) + Antiemetic prophylaxis
Combination Product: Erlotinib plus Romidepsin (10 mg/m^2)
Combination Product: Erlotinib plus Romidepsin (8 mg/m^2)
Combination Product: Erlotinib plus Romidepsin (10 mg/m^2) + Antiemetic prophylaxis

Registration Number: NCT01302808

Lead Sponsor: University of Texas Southwestern Medical Center

Brief Summary: RATIONALE: Romidepsin and erlotinib hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

PURPOSE: This phase I/II trial is studying the side effects and best dose of romidepsin when given together with erlotinib hydrochloride and to see how well they work in treating patients with stage III or stage IV non-small cell lung cancer.

Detailed Description: OBJECTIVES:

Primary

* 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)

Secondary

* To characterize the pharmacokinetic profile of romidepsin in combination with erlotinib hydrochloride.

* 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 (epidermal growth factor receptor)-signaling pathway in skin biopsies, particularly downstream mediators such as MAPK (mitogen-activated protein kinase). (Exploratory)

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 17

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Cohort 4 (Erlotinib plus Romidepsin (8 mg/m^2)) + Antiemetic prophylaxis	(Erlotinib plus Romidepsin (8mg/m^2)) + Antiemetic prophylaxis	Erlotinib 150 mg orally daily plus romidepsin IV days 8 mg/m\^2 with antiemetic prophylaxis administered as a 4-h intravenous infusion on days 1, 8, and 15 of a 28-day cycle.
Cohort 2 (Erlotinib plus Romidepsin (10 mg/m^2))	Erlotinib plus Romidepsin (10 mg/m^2)	Erlotinib 150 mg orally daily plus romidepsin IV days 10 mg/m\^2 administered as a 4-h intravenous infusion on days 1, 8, and 15 of a 28-day cycle.
Cohort 1 (Erlotinib plus Romidepsin (8 mg/m^2))	Erlotinib plus Romidepsin (8 mg/m^2)	Erlotinib 150 mg orally daily plus romidepsin IV days 8 mg/m\^2 administered as a 4-h intravenous infusion on days 1, 8, and 15 of a 28-day cycle.
Cohort 3 (Erlotinib plus Romidepsin (10 mg/m^2)) + Antiemetic prophylaxis	Erlotinib plus Romidepsin (10 mg/m^2) + Antiemetic prophylaxis	Erlotinib 150 mg orally daily plus romidepsin IV days 10 mg/m\^2 with antiemetic prophylaxis administered as a 4-h intravenous infusion on days 1, 8, and 15 of a 28-day cycle.

Primary Outcome Measures

Name	Time	Method
Number of Participants With Dose Limiting Toxicities and Maximum Tolerated Dose (MTD)	12 months	Dose limiting toxicities per Protocol definition using (CTCAE), Version 3.0

Secondary Outcome Measures

Name	Time	Method
Area Under the Concentration-time Curve (AUC0 t) of Romidepsin in Combination With Erlotinib	0, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72 hours post-dose on Days 1 and 8	AUC0 t was measured in the time interval from 0 to time (t) when the last blood sample is collected with a concentration above the limit of quantification.