Clinical Trials /

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

NCT01857271

Description:

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.

Related Conditions:
  • Non-Small Cell Lung Carcinoma
Recruiting Status:

Terminated

Phase:

Phase 2

Trial Eligibility

Document

<span class="go-doc-concept go-doc-intervention">Erlotinib Hydrochloride</span> Before Surgery in Treating Patients With Stage III Non-Small Cell <span class="go-doc-concept go-doc-disease">Lung Cancer</span>

Title

  • Brief Title: Erlotinib Hydrochloride Before Surgery in Treating Patients With Stage III Non-Small Cell Lung Cancer
  • Official Title: EValuation of Erlotinib as a Neoadjuvant Therapy in Stage III NSCLC Patients With EGFR Mutations (EVENT Trial)
  • Clinical Trial IDs

    NCT ID: NCT01857271

    ORG ID: 2013-233

    NCI ID: NCI-2013-02219

    Trial Conditions

    Stage IIIB Non-Small Cell Lung Cancer

    Stage IIIA Non-Small Cell Lung Cancer

    Trial Interventions

    Drug Synonyms Arms
    Erlotinib Hydrochloride Cp-358,774 Treatment (erlotinib hydrochloride and thoracotomy)

    Trial Purpose

    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.

    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.

    Trial Arms

    Name Type Description Interventions
    Treatment (erlotinib hydrochloride and thoracotomy) Experimental Patients receive erlotinib hydrochloride PO QD for 2 months and then undergo thoracotomy. Erlotinib Hydrochloride

    Eligibility Criteria

    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

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    Rate of mediastinal nodal clearance, defined as pathologically negative N2 disease in the final surgical resection specimen or mediastinoscopy

    Rate of complete pathological response

    Secondary Outcome Measures

    Objective overall response rate (ORR, i.e., complete response [CR] + partial response [PR])

    Disease control rate (CR + PR+ stable disease)

    Surgical resection rate

    Progression free survival (PFS)

    Overall survival (OS)

    Incidence of toxicity, scored using National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0

    Trial Keywords