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Erlotinib Hydrochloride or Crizotinib and Chemoradiation Therapy in Treating Patients With Stage III Non-small Cell Lung Cancer

NCT01822496

Description:

This randomized phase II trial studies how well erlotinib hydrochloride or crizotinib with chemoradiation therapy works in treating patients with stage III non-small cell lung cancer. Radiation therapy uses high energy x rays to kill tumor cells. Specialized radiation therapy that delivers a high dose of radiation directly to the tumor may kill more tumor cells and cause less damage to normal tissue. Drugs used in chemotherapy, such as cisplatin, etoposide, paclitaxel, and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. It is not yet known whether giving erlotinib hydrochloride is more effective than crizotinib with chemoradiation therapy in treating patients with non-small cell lung cancer.

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> or <span class="go-doc-concept go-doc-intervention">Crizotinib</span> and <span class="go-doc-concept go-doc-intervention">Chemoradiation</span> Therapy 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 or Crizotinib and Chemoradiation Therapy in Treating Patients With Stage III Non-small Cell Lung Cancer
  • Official Title: A Randomized Phase II Study of Individualized Combined Modality Therapy for Stage III Non-small Cell Lung Cancer (NSCLC)
  • Clinical Trial IDs

    NCT ID: NCT01822496

    ORG ID: NCI-2013-00737

    NCI ID: NCI-2013-00737

    Trial Conditions

    Stage IIIB Non-Small Cell Lung Cancer

    Stage IIIA Non-Small Cell Lung Cancer

    Trial Interventions

    Drug Synonyms Arms
    Carboplatin Blastocarb, Carboplat, CARBOPLATIN, Carboplatin Hexal, Carboplatino, Carbosin, Carbosol, Carbotec, CBDCA, Displata, Ercar, JM-8, Nealorin, Novoplatinum, Paraplat, Paraplatin, Paraplatin AQ, Paraplatine, Platinwas, Ribocarbo Arm I (erlotinib hydrochloride, concurrent chemoradiation), Arm III (crizotinib, concurrent chemoradiation), Arm II (chemoradiation, EGFR TK Mutation Cohort), Arm IV (chemoradiation, ALK Tran L Cohort)
    Cisplatin Abiplatin, Blastolem, Briplatin, CDDP, Cis-diammine-dichloroplatinum, Cis-diamminedichloridoplatinum, Cis-diamminedichloro Platinum (II), Cis-diamminedichloroplatinum, Cis-dichloroammine Platinum (II), Cis-platinous Diamine Dichloride, Cis-platinum, Cis-platinum II, Cis-platinum II Diamine Dichloride, Cismaplat, CISPLATIN, Cisplatina, Cisplatinum, Cisplatyl, Citoplatino, Citosin, Cysplatyna, DDP, Lederplatin, Metaplatin, Neoplatin, Peyrone's Chloride, Peyrone's Salt, Placis, Plastistil, Platamine, Platiblastin, Platiblastin-S, Platinex, Platinol, Platinol- AQ, Platinol-AQ, Platinol-AQ VHA Plus, Platinoxan, Platinum, Platinum Diamminodichloride, Platiran, Platistin, Platosin Arm I (erlotinib hydrochloride, concurrent chemoradiation), Arm III (crizotinib, concurrent chemoradiation), Arm II (chemoradiation, EGFR TK Mutation Cohort), Arm IV (chemoradiation, ALK Tran L Cohort)
    Crizotinib CRIZOTINIB, MET Tyrosine Kinase Inhibitor PF-02341066, PF-02341066, PF-2341066, Xalkori Arm III (crizotinib, concurrent chemoradiation)
    Erlotinib Hydrochloride Cp-358,774, ERLOTINIB HYDROCHLORIDE, OSI-774, Tarceva Arm I (erlotinib hydrochloride, concurrent chemoradiation)
    Etoposide Demethyl Epipodophyllotoxin Ethylidine Glucoside, EPEG, ETOPOSIDE, Lastet, Toposar, Vepesid, VP 16-213, VP-16, VP-16-213 Arm I (erlotinib hydrochloride, concurrent chemoradiation), Arm III (crizotinib, concurrent chemoradiation), Arm II (chemoradiation, EGFR TK Mutation Cohort), Arm IV (chemoradiation, ALK Tran L Cohort)
    Paclitaxel Anzatax, Asotax, Bristaxol, PACLITAXEL, Praxel, Taxol, Taxol Konzentrat Arm I (erlotinib hydrochloride, concurrent chemoradiation), Arm III (crizotinib, concurrent chemoradiation), Arm II (chemoradiation, EGFR TK Mutation Cohort), Arm IV (chemoradiation, ALK Tran L Cohort)

    Trial Purpose

    This randomized phase II trial studies how well erlotinib hydrochloride or crizotinib with
    chemoradiation therapy works in treating patients with stage III non-small cell lung cancer.
    Radiation therapy uses high energy x rays to kill tumor cells. Specialized radiation therapy
    that delivers a high dose of radiation directly to the tumor may kill more tumor cells and
    cause less damage to normal tissue. Drugs used in chemotherapy, such as cisplatin,
    etoposide, paclitaxel, and carboplatin, work in different ways to stop the growth of tumor
    cells, either by killing the cells, by stopping them from dividing, or by stopping them from
    spreading. It is not yet known whether giving erlotinib hydrochloride is more effective than
    crizotinib with chemoradiation therapy in treating patients with non-small cell lung cancer.

    Detailed Description

    PRIMARY OBJECTIVES:

    I. To assess whether patients with unresectable local-regionally advanced non-small cell
    lung cancer (NSCLC) treated with targeted agents based on molecular characteristics have a
    longer progression-free survival than those treated with standard care therapy alone.

    SECONDARY OBJECTIVES:

    I. To evaluate response rate. II. To assess toxicity. III. To assess overall survival. IV.
    To correlate clinical outcomes with tumor molecular aberrations identified from deep
    sequencing of selected kinomes in patients from whom adequate baseline tissue is available.

    OUTLINE: Patients are randomized to 1 of 4 treatment arms.

    ARM I (induction therapy): Patients receive erlotinib hydrochloride orally (PO) once daily
    (QD) for up to 12 weeks. Patients who have had no response (partial or complete) after 6
    weeks undergo concurrent chemoradiation therapy immediately. After 2 weeks of completion of
    induction therapy, patients receive chemoradiation.

    ARM III (induction therapy): Patients receive crizotinib PO twice daily (BID) for up to 12
    weeks. Patients who have had no response (partial or complete) after 6 weeks undergo
    concurrent chemoradiation therapy immediately. After 2 weeks of completion of induction
    therapy, patients receive chemoradiation.

    ARMS II AND IV (concurrent chemoradiation): Patients receive concurrent chemotherapy with
    thoracic radiation therapy beginning on day 1. Treatment continues in the absence of disease
    progression or unacceptable toxicity.

    CHEMORADIATION: In all treatment arms, patients undergo concurrent intensity modulated
    radiation therapy (IMRT) or 3-dimensional conformal radiation therapy (3-D CRT) QD 5 days a
    week for 6 weeks. Patients receive 1 of 2 chemotherapy regimens based on the discretion of
    the treating physician. Patients receive cisplatin intravenously (IV) over 1-2 hours on days
    1, 8, 29, and 36 and etoposide IV over 1 hour on days 1-5 and 29-33. Treatment repeats every
    4 weeks for up to 2 courses in the absence of disease progression or unacceptable toxicity.
    Some patients receive paclitaxel IV and carboplatin IV on days 1, 8, 15, 22, 29, and 36
    during radiation therapy for 6 weeks. Two courses of consolidation treatment will begin 4-6
    weeks after completion of radiation therapy with paclitaxel IV on days 1 and 22 and
    carboplatin IV on days 1 and 22 in the absence of disease progression or unacceptable
    toxicity.

    After completion of study treatment, patients are followed up at 1 month, every 3 months for
    2 years, every 6 months for 3 years, and then annually for 5 years.

    Trial Arms

    Name Type Description Interventions
    Arm I (erlotinib hydrochloride, concurrent chemoradiation) Experimental Patients receive erlotinib hydrochloride PO QD for up to 12 weeks. Patients who have had no response (partial or complete) after 6 weeks undergo concurrent chemoradiation therapy immediately. After 2 weeks of completion of induction therapy, patients receive chemoradiation. Carboplatin, Cisplatin, Erlotinib Hydrochloride, Etoposide, Paclitaxel
    Arm II (chemoradiation, EGFR TK Mutation Cohort) Active Comparator Patients receive concurrent chemotherapy with thoracic radiation therapy beginning on day 1. Treatment continues in the absence of disease progression or unacceptable toxicity. Carboplatin, Cisplatin, Etoposide, Paclitaxel
    Arm III (crizotinib, concurrent chemoradiation) Experimental Patients receive crizotinib PO BID for up to 12 weeks. Patients who have had no response (partial or complete) after 6 weeks undergo concurrent chemoradiation therapy immediately. After 2 weeks of completion of induction therapy, patients receive chemoradiation. Carboplatin, Cisplatin, Crizotinib, Etoposide, Paclitaxel
    Arm IV (chemoradiation, ALK Tran L Cohort) Active Comparator Patients receive concurrent chemotherapy with thoracic radiation therapy beginning on day 1. Treatment continues in the absence of disease progression or unacceptable toxicity. Carboplatin, Cisplatin, Etoposide, Paclitaxel

    Eligibility Criteria

    Inclusion Criteria:

    - Histologically or cytologically confirmed, newly diagnosed non-squamous NSCLC

    - Unresectable stage IIIA or IIIB disease; patients must be surgically staged to
    confirm N2 or N3 disease; patients may have invasive mediastinal staging by
    mediastinoscopy, mediastinotomy, endobronchial ultrasound transbronchial aspiration
    (EBUS-TBNA), endoscopic ultrasound (EUS), or video-assisted thoracoscopic surgery
    (VATS)

    - Patients with any tumor (T) with node (N)2 or N3 are eligible; patients with T3,
    N1-N3 disease are eligible if deemed unresectable; patients with T4, any N are
    eligible

    - Patients must have measurable disease, i.e., lesions that can be accurately measured
    in at least 1 dimension (longest dimension in the plane of measurement is to be
    recorded) with a minimum size of 10 mm by computed tomography (CT) scan (CT scan
    slice thickness no greater than 5 mm)

    - Patients with a pleural effusion, which is a transudate, cytologically negative and
    non-bloody, are eligible if the radiation oncologist feels the tumor can be
    encompassed within a reasonable field of radiotherapy

    - If a pleural effusion can be seen on the chest CT but not on chest x-ray and is too
    small to tap, the patient will be eligible; patients who develop a new pleural
    effusion after thoracotomy or other invasive thoracic procedure will be eligible

    - The institution's pre-enrollment biomarker screening at a Clinical Laboratory
    Improvement Amendments (CLIA) certified lab documents presence of known "sensitive"
    mutations in epidermal growth factor receptor tyrosine kinase (EGFR TK) domain (exon
    19 deletion, L858) and/or EML4-anaplastic lymphoma kinase (ALK) fusion arrangement;
    either the primary tumor or the metastatic lymph node tissue may be used for testing
    of mutations

    - The institution's pre-enrollment biomarker screening at a CLIA certified lab
    documents absence of T790M mutation in the EGFR TK domain

    - Appropriate stage for protocol entry, including no distant metastases, based upon the
    following minimum diagnostic workup:

    - History/physical examination, including recording of pulse, blood pressure (BP),
    weight, and body surface area, within 45 days prior to registration

    - Whole body fludeoxyglucose-positron emission tomography (FDG-PET)/CT (orbits to
    mid-thighs) within 30 days prior to registration; PET/CT must be negative for
    distant metastasis

    - CT scan with contrast of the chest and upper abdomen to include liver and
    adrenals (unless medically contraindicated) within 30 days prior to registration

    - Magnetic resonance imaging (MRI) of the brain with contrast (or CT scan with
    contrast, if MRI medically contraindicated) within 30 days prior to registration

    - Zubrod performance status 0-1 within 14 days prior to registration

    - Absolute neutrophil count (ANC) >= 1,000 cells/mm^3

    - Platelets >= 100,000 cells/mm^3

    - Hemoglobin >= 8.0 g/dl (Note: the use of transfusion or other intervention to achieve
    hemoglobin [Hgb] >= 8.0 g/dl is acceptable)

    - Serum creatinine < 1.5 mg/dL or calculated creatinine clearance >= 50 ml/min (by
    Cockcroft-Gault formula) within 14 days prior to registration

    - Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 2.5 x upper limit
    of normal (ULN) within 14 days prior to registration

    - Bilirubin within normal institutional limits within 14 days prior to registration

    - Negative serum pregnancy test within 14 days prior to registration for women of
    childbearing potential

    - Patient must provide study specific informed consent prior to study entry, including
    consent for mandatory screening of tissue

    Exclusion Criteria:

    - Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free
    for a minimum of 730 days (2 years) (for example, carcinoma in situ of the breast,
    oral cavity, or cervix are all permissible)

    - Prior systemic chemotherapy for the study cancer; note that prior chemotherapy for a
    different cancer is allowable

    - Prior radiotherapy to the region of the study cancer that would result in overlap of
    radiation therapy fields

    - Atelectasis of the entire lung

    - Contralateral hilar node involvement

    - Exudative, bloody, or cytologically malignant effusions

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

    - Unstable angina and/or congestive heart failure requiring hospitalization within
    the last 6 months

    - Transmural myocardial infarction within the last 6 months

    - Acute bacterial or fungal infection requiring intravenous antibiotics at the
    time of registration

    - Chronic obstructive pulmonary disease exacerbation or other respiratory illness
    requiring hospitalization or precluding study therapy at the time of
    registration; hepatic insufficiency resulting in clinical jaundice and/or
    coagulation defects

    - Acquired immune deficiency syndrome (AIDS) based upon current Centers for
    Disease Control and Prevention (CDC) definition; note, however, that human
    immunodeficiency virus (HIV) testing is not required for entry into this
    protocol; protocol-specific requirements may also exclude immuno-compromised
    patients

    - Pregnancy or women of childbearing potential and men who are sexually active and not
    willing/able to use medically acceptable forms of contraception

    - Prior allergic reaction to the study drug(s) involved in this protocol

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    Progression-free survival

    Secondary Outcome Measures

    Deep sequencing of selected kinomes in patients from whom adequate baseline tissue is available

    Distant progression free survival

    Incidence of grade 3-5 adverse events, graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events v4.0

    Local-regional progression free survival

    Overall survival

    Proportion of patients who respond (completely or partially) to each treatment, assessed by the Response Evaluation Criteria in Solid Tumors

    Trial Keywords