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

This study has been completed.
Celgene Corporation
Genentech, Inc.
Information provided by (Responsible Party):
University of Texas Southwestern Medical Center Identifier:
First received: February 19, 2011
Last updated: May 29, 2015
Last verified: May 2015

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.

Condition Intervention Phase
Lung Cancer
Metastatic Cancer
Drug: erlotinib hydrochloride
Drug: romidepsin
Other: laboratory biomarker analysis
Other: pharmacological study
Phase 1
Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I/II Study of Erlotinib and Romidepsin in Advanced Non-Small Cell Lung Cancer

Resource links provided by NLM:

Further study details as provided by University of Texas Southwestern Medical Center:

Primary Outcome Measures:
  • Toxicity of erlotinib hydrochloride plus romidepsin
  • Maximum-tolerated dose (MTD) of erlotinib hydrochloride plus romidepsin

Secondary Outcome Measures:
  • Time to response, progression-free survival, and overall survival
  • Pharmacokinetic profile of romidepsin in combination with erlotinib hydrochloride

Enrollment: 18
Study Start Date: September 2009
Study Completion Date: December 2014
Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Detailed Description:



  • 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.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No


  • 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
  Contacts and Locations
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Please refer to this study by its identifier: NCT01302808

United States, Texas
Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas
Dallas, Texas, United States, 75390
Sponsors and Collaborators
University of Texas Southwestern Medical Center
Celgene Corporation
Genentech, Inc.
Principal Investigator: David E. Gerber, MD Simmons Cancer Center
  More Information

Responsible Party: University of Texas Southwestern Medical Center Identifier: NCT01302808     History of Changes
Other Study ID Numbers: SCCC-12508
CDR0000653093 ( Registry Identifier: PDQ (Physician Data Query) )
NCI-2011-01035 ( Registry Identifier: CTRP (Clinical Trials Reporting System) )
Study First Received: February 19, 2011
Last Updated: May 29, 2015

Keywords provided by University of Texas Southwestern Medical Center:
recurrent non-small cell lung cancer
stage IIIB non-small cell lung cancer
stage IV non-small cell lung cancer
malignant pleural effusion
adenocarcinoma of the lung
adenosquamous cell lung cancer
bronchoalveolar cell lung cancer
large cell lung cancer
squamous cell lung cancer

Additional relevant MeSH terms:
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Neoplasm Metastasis
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Neoplastic Processes
Pathologic Processes
Erlotinib Hydrochloride
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antibiotics, Antineoplastic processed this record on March 29, 2017