Erlotinib Hydrochloride Before Surgery in Treating Patients With Stage III Non-Small Cell Lung Cancer (EVENT)

EValuation of Erlotinib as a Neoadjuvant Therapy in Stage III NSCLC Patients With EGFR Mutations (EVENT Trial)

This phase II trial studies how well erlotinib hydrochloride works before surgery in treating patients with stage III non-small cell lung cancer. Erlotinib hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving erlotinib hydrochloride before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed.

Study Overview

• Status: Terminated
• Conditions: Stage IIIA Non-Small Cell Lung Cancer; Stage IIIB Non-Small Cell Lung Cancer
• Intervention / Treatment: Drug: Erlotinib Hydrochloride; Procedure: Therapeutic Conventional Surgery; Other: Laboratory Biomarker Analysis

Detailed Description

PRIMARY OBJECTIVES:

I. To estimate the rate of mediastinal nodal clearance and complete pathological response after neoadjuvant erlotinib (erlotinib hydrochloride) in patients with epidermal growth factor receptor (EGFR) mutated stage III non-small cell lung cancer (NSCLC).

SECONDARY OBJECTIVES:

I. To determine the progression free survival in patient population of EGFR mutated stage III NSCLC patients who are treated with neoadjuvant erlotinib therapy.

II. To determine the overall survival. III. To estimate the overall response rate from neoadjuvant erlotinib. IV. To estimate the surgical resection rate. V. To evaluate the safety of neoadjuvant erlotinib.

TERTIARY OBJECTIVES:

I. To determine several molecular and cellular biomarkers in the tumors, the skin and the serum that are predictive of the efficacy of neoadjuvant erlotinib.

OUTLINE:

Patients receive erlotinib hydrochloride orally (PO) once daily (QD) for 2 months and then undergo thoracotomy.

After completion of study treatment, patients are followed up at 30 days, every 3 months for 1 year, and then every 6 months for 5 years.

• Study Type: Interventional
• Enrollment (Actual): 3
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • New York
    • Bronx, New York, United States, 10461
      • Albert Einstein College Of Medicine
    • New York, New York, United States, 10032
      • Columbia University Medical Center
    • New York, New York, United States, 10065
      • Weill Cornell Medical College

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Pathologically proven (either histologic or cytologic) diagnosis of stage IIIA or IIIB non-small cell lung cancer; (according to American Joint Committee on Cancer [AJCC] staging, 7th edition) within 4 weeks of registration; the patient should have histologically or cytologically confirmed N2 disease
• Activating mutation in EGFR
• No prior chemotherapy or radiation for lung cancer
• Patients may be potentially resectable or unresectable

• Stage III A or B disease, including no distant metastases- based on following diagnostic workup:

  • History/physical examination prior to registration
  • Computed tomography (CT) scan of the chest or positron emission tomography (PET) scan within 28 days of study entry
  • CT scan of abdomen or magnetic resonance imaging (MRI) of abdomen or PET scan within 28 days of study entry
  • An MRI of the brain or head CT scan with contrast within 28 days of study entry
  • Total body PET scan within 28 days of study entry
  • Mediastinoscopies are highly recommended
• Patients must have measurable or evaluable disease
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2
• Absolute neutrophil count (ANC) >= 1,500 cells/ul
• Platelets >= 100,000 cells/ul
• Hemoglobin >= 9.0 g/dl (note: the use of transfusion or other intervention to achieve hemoglobin [Hgb] >= g/dl is acceptable)
• Serum creatinine =< 1.5 x upper limit of normal (ULN)
• Total bilirubin < 2.0 times the institutional upper limit of normal (ULN)
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 x the ULN

• Women of childbearing potential must have:

  • A negative serum or urine pregnancy test (sensitivity =< 25 IU human chorionic gonadotropin [HCG]/L) within 72 hours prior to the start of study drug administration
  • Persons of reproductive potential must agree to use and utilize an adequate method of contraception throughout treatment and for at least 4 weeks after study drug is stopped prior to study enrollment, women of childbearing potential must be advised of the importance of avoiding pregnancy during trial participation and the potential risk factors for an unintentional pregnancy
• Ability to take oral medication
• Patient must sign study specific informed consent prior to study entry

Exclusion Criteria:

• Pleural or pericardial effusion

  • Pleural effusions allowed if one of the following conditions are met: 1) negative cytology after adequate sampling by thoracentesis 2) effusion seen on CT scan but not on chest x-ray and deemed too small to tap under CT or ultrasound guidance

• Severe, active co-morbidity, defined as follows:

  • Cardiac symptoms; any of the following should be considered for exclusion:

    • Uncontrolled angina, congestive heart failure or myocardial infarction (MI) within (6 months)
    • Diagnosed congenital long QT syndrome
    • Any history of clinically significant ventricular arrhythmias (such as ventricular tachycardia, ventricular fibrillation, or Torsades de pointes)
    • Prolonged corrected QT (QTc) interval on pre-entry electrocardiogram (> 450 msec)

• History of significant bleeding disorder unrelated to cancer, including:

  • Diagnosed congenital bleeding disorders (e.g., von Willebrand's disease)
  • Diagnosed acquired bleeding disorder within one year (e.g., acquired anti-factor VIII antibodies)
  • Ongoing or recent (=< 3 months) significant gastrointestinal bleeding
• Prisoners or subjects who are compulsorily detained (involuntarily incarcerated) for treatment of either a psychiatric or physical (e.g., infectious) illness

• Men and women who:

  • Are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period and for at least 4 weeks after cessation of study drug, or women who:

    • Have a positive pregnancy test at baseline, or
    • Are pregnant or breastfeeding

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment (erlotinib hydrochloride and thoracotomy); Patients receive erlotinib hydrochloride PO QD for 2 months and then undergo thoracotomy.	Drug: Erlotinib Hydrochloride; Given PO; Other Names: Cp-358,774; Procedure: Therapeutic Conventional Surgery; Undergo thoracotomy; Other: Laboratory Biomarker Analysis; Correlative studies

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Rate of Mediastinal Nodal Clearance, Defined as Pathologically Negative N2 Disease in the Final Surgical Resection Specimen or Mediastinoscopy	3 years 9 months

Collaborators and Investigators

• Sponsor: Albert Einstein College of Medicine
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Haiying Cheng, Albert Einstein College Of Medicine

Study record dates

Study Major Dates

• Study Start: November 1, 2013
• Primary Completion (Actual): August 31, 2017
• Study Completion (Actual): August 31, 2017

Study Registration Dates

• First Submitted: May 16, 2013
• First Submitted That Met QC Criteria: May 16, 2013
• First Posted (Estimate): May 20, 2013

Study Record Updates

• Last Update Posted (Actual): July 8, 2020
• Last Update Submitted That Met QC Criteria: June 24, 2020
• Last Verified: June 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Erlotinib Hydrochloride
• Other Study ID Numbers: 2013-233 (Other Identifier: Albert Einstein College of Medicine); NCI-2013-02219 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); 2013-233-004; P30CA013330 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes