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

The recruitment status of this study is unknown because the information has not been verified recently.
Verified September 2009 by National Cancer Institute (NCI).
Recruitment status was  Recruiting
Sponsor:
Information provided by:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT01302808
First received: February 19, 2011
Last updated: February 22, 2011
Last verified: September 2009
  Purpose

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
Neoplasm Metastasis
Drug: erlotinib hydrochloride
Drug: romidepsin
Other: laboratory biomarker analysis
Other: pharmacological study
Phase 1
Phase 2

Study Type: Interventional
Study Design: 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 National Cancer Institute (NCI):

Primary Outcome Measures:
  • Toxicity of erlotinib hydrochloride plus romidepsin [ Designated as safety issue: Yes ]
  • Maximum-tolerated dose (MTD) of erlotinib hydrochloride plus romidepsin [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Time to response, progression-free survival, and overall survival [ Designated as safety issue: No ]
  • Pharmacokinetic profile of romidepsin in combination with erlotinib hydrochloride [ Designated as safety issue: No ]

Estimated Enrollment: 39
Study Start Date: September 2009
Estimated Primary Completion Date: August 2012 (Final data collection date for primary outcome measure)
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-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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • 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

PATIENT CHARACTERISTICS:

  • 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

PRIOR CONCURRENT THERAPY:

  • 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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01302808

Locations
United States, Texas
Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas Recruiting
Dallas, Texas, United States, 75390
Contact: Clinical Trials Office - Simmons Comprehensive Cancer Center a    866-460-4673; 214-648-7097      
Sponsors and Collaborators
Simmons Cancer Center
Investigators
Principal Investigator: David E. Gerber, MD Simmons Cancer Center
Investigator: Erin Fenske, BA, MBA Simmons Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: David E. Gerber, Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas
ClinicalTrials.gov Identifier: NCT01302808     History of Changes
Other Study ID Numbers: CDR0000653093, SCCC-12508
Study First Received: February 19, 2011
Last Updated: February 22, 2011
Health Authority: Unspecified

Keywords provided by National Cancer Institute (NCI):
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:
Neoplasms
Carcinoma, Non-Small-Cell Lung
Lung Neoplasms
Neoplasm Metastasis
Carcinoma, Bronchogenic
Bronchial Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases
Neoplastic Processes
Pathologic Processes
Erlotinib
Romidepsin
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antibiotics, Antineoplastic
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on July 23, 2014