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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01302808
Recruitment Status : Completed
First Posted : February 24, 2011
Last Update Posted : June 1, 2015
Celgene Corporation
Genentech, Inc.
Information provided by (Responsible Party):
University of Texas Southwestern Medical Center

February 19, 2011
February 24, 2011
June 1, 2015
September 2009
December 2014   (Final data collection date for primary outcome measure)
  • Toxicity of erlotinib hydrochloride plus romidepsin
  • Maximum-tolerated dose (MTD) of erlotinib hydrochloride plus romidepsin
Same as current
Complete list of historical versions of study NCT01302808 on Archive Site
  • Time to response, progression-free survival, and overall survival
  • Pharmacokinetic profile of romidepsin in combination with erlotinib hydrochloride
Same as current
Not Provided
Not Provided
Romidepsin and Erlotinib Hydrochloride in Treating Patients With Stage III or Stage IV Non-Small Cell Lung Cancer
A Phase I/II Study of Erlotinib and Romidepsin in Advanced Non-Small Cell Lung Cancer

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.



  • 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 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-signaling pathway in skin biopsies, particularly downstream mediators such as MAPK. (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.

Phase 1
Phase 2
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
  • Lung Cancer
  • Metastatic Cancer
  • Drug: erlotinib hydrochloride
  • Drug: romidepsin
  • Other: laboratory biomarker analysis
  • Other: pharmacological study
Not Provided
Not Provided

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
December 2014
December 2014   (Final data collection date for primary outcome measure)


  • Histologically confirmed locally advanced or metastatic (stage IIIB pleural effusion or stage IV) non-small cell lung cancer (NSCLC), including the following cell types:

    • Squamous cell carcinoma
    • Adenocarcinoma
    • Adenosquamous carcinoma
    • Large cell carcinoma
    • Large cell neuroendocrine
    • Carcinoma not otherwise specified
  • Measurable disease as defined by RECIST
  • Clinically stable brain metastases are permitted


  • ECOG performance status 0-1
  • Serum potassium ≥ 3.8 mmol/L and magnesium ≥ 2.0 mg/dL

    • Electrolyte abnormalities may be corrected with supplementation
  • Hemoglobin ≥ 10 g/dL (transfusions and/or erythropoietin-stimulating agents are permitted)
  • ANC ≥ 1,500/mm³
  • Platelet count ≥ 100,000/mm³
  • Total bilirubin < 1.5 times upper limit of normal (ULN)
  • AST and ALT < 2.0 times ULN (< 3 times ULN in the presence of demonstrable liver metastases)
  • Serum creatinine < 2.0 times ULN
  • Not pregnant or nursing
  • Negative urine or serum pregnancy test
  • Women of childbearing potential and men must use an effective barrier method of contraception (e.g., an intrauterine contraception device [IUCD], double-barrier method using condoms, or a diaphragm plus spermicide) during the treatment period and for at least 1 month thereafter
  • No known cardiac abnormalities, including any of the following:

    • Congenital long QT syndrome
    • QTc interval > 480 msec
    • Myocardial infarction within 12 months prior to study entry
    • Other significant electrocardiogram (ECG) abnormalities, including type II second- or third-degree atrio-ventricular (AV) block, or bradycardia (ventricular rate < 50 beats/min)
    • History of coronary artery disease (CAD) (e.g., angina Canadian class II-IV)

      • For any patients in whom there is doubt, a stress-imaging study should be performed and if abnormal, an angiography should also be performed to define whether or not CAD is present
    • An ECG recorded at screening showing significant ST depression (ST depression of ≥ 2 mm, measured from isoelectric line to the ST segment at a point 60 msec from the end of the QRS complex)
    • NYHA class II to IV congestive heart failure (CHF), and/or ejection fraction (EF) < 40% by MUGA scan or < 50% by ECG and/or MRI
    • Known history of sustained ventricular tachycardia (VT), ventricular fibrillation (VF), Torsades de Pointes, or cardiac arrest, unless currently addressed with an automatic implantable cardiac defibrillator (AICD)
    • Hypertrophic cardiomyopathy or restrictive cardiomyopathy from prior treatment or other causes
    • Uncontrolled hypertension defined as blood pressure ≥ 160/95 mm Hg
    • Any cardiac arrhythmia requiring anti-arrhythmia medication
  • No clinically significant active systemic, pulmonary, or pericardial infection, including known HIV infection and hepatitis B or C
  • No significant medical or psychiatric condition that might prevent the patient from complying with all study procedures


  • At least 3 weeks since prior erlotinib hydrochloride (phase I)
  • At least 3 weeks since prior anti-cancer therapy or, at the discretion of the investigator, may be treatment-naive (phase I)
  • At least 1 and no more than 2 prior chemotherapy regimens for advanced NSCLC (phase II)
  • At least 3 weeks since prior chemotherapy for NSCLC
  • At least 2 weeks since prior major surgery or radiation therapy
  • No prior erlotinib hydrochloride (phase II)
  • No prior romidepsin
  • No other concurrent anti-cancer therapy
  • No prior or concurrent investigational agent within 4 weeks prior to study entry
  • No concurrent drugs that may cause a prolongation of the QTc interval
  • No concurrent CYP3A4 inhibitors
  • No concurrent warfarin
Sexes Eligible for Study: All
18 Years and older   (Adult, Older Adult)
Contact information is only displayed when the study is recruiting subjects
United States
CDR0000653093 ( Registry Identifier: PDQ (Physician Data Query) )
NCI-2011-01035 ( Registry Identifier: CTRP (Clinical Trials Reporting System) )
Not Provided
Not Provided
Not Provided
University of Texas Southwestern Medical Center
University of Texas Southwestern Medical Center
  • Celgene Corporation
  • Genentech, Inc.
Principal Investigator: David E. Gerber, MD Simmons Cancer Center
University of Texas Southwestern Medical Center
May 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP