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A Phase I/II Study of Erlotinib and Romidepsin in Advanced Non-Small Cell Lung Cancer

Phase 1/Phase 2
18 Years
Open (Enrolling)
Lung Cancer, Neoplasm Metastasis

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Trial Information

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
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.

Inclusion Criteria


- 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

- 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

- 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

- 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

Type of Study:


Study Design:

Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Toxicity of erlotinib hydrochloride plus romidepsin

Safety Issue:


Principal Investigator

David E. Gerber, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Simmons Cancer Center



Study ID:




Start Date:

September 2009

Completion Date:

Related Keywords:

  • Lung Cancer
  • Neoplasm Metastasis
  • 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
  • Neoplasms
  • Carcinoma, Non-Small-Cell Lung
  • Lung Neoplasms
  • Neoplasm Metastasis



Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas Dallas, Texas  75390