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

A Randomized Phase II Study of Individualized Combined Modality Therapy for Stage III Non-small Cell Lung Cancer (NSCLC)

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.

Study Overview

• Status: Terminated
• Conditions: Stage IIIA Non-Small Cell Lung Cancer AJCC v7; Stage III Non-Small Cell Lung Cancer AJCC v7; Stage IIIB Non-Small Cell Lung Cancer AJCC v7
• Intervention / Treatment: Radiation: Radiation Therapy; Drug: Carboplatin; Drug: Cisplatin; Drug: Erlotinib; Drug: Etoposide; Drug: Paclitaxel; Drug: Crizotinib

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: Eligible patients are assigned to one of two cohorts based on pre-enrollment screening by the enrolling institution for two biomarkers: EGFR TK mutation and EML4-ALK fusion arrangement. Within each cohort, patients are randomized to either an experimental or control arm, resulting in a total of four treatment arms overall. Patients with both the EGFR mutation and ALK arrangement are placed in the ALK Cohort.

Planned Sample Size: 156 for the EGFR mutation cohort and 78 for the ALK translocation cohort

After completion of study treatment, patients are followed at 1 and 2 months, 4-6 weeks, every 3 months for 2 years, every 6 months for 3 years, and then annually for 5 years.

• Study Type: Interventional
• Enrollment (Actual): 59
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • University of Alabama at Birmingham Cancer Center
  • Alaska
    • Anchorage, Alaska, United States, 99508
      • Providence Alaska Medical Center
  • Arizona
    • Gilbert, Arizona, United States, 85234
      • Banner MD Anderson Cancer Center
    • Scottsdale, Arizona, United States, 85259
      • Mayo Clinic in Arizona
  • California
    • Bakersfield, California, United States, 93301
      • AIS Cancer Center at San Joaquin Community Hospital
    • La Jolla, California, United States, 92093
      • UC San Diego Moores Cancer Center
    • Marysville, California, United States, 95901
      • Fremont - Rideout Cancer Center
    • Merced, California, United States, 95340
      • Mercy UC Davis Cancer Center
    • Palo Alto, California, United States, 94304
      • Stanford Cancer Institute Palo Alto
    • Sacramento, California, United States, 95817
      • University of California Davis Comprehensive Cancer Center
    • Saint Helena, California, United States, 94574
      • Saint Helena Hospital
    • San Francisco, California, United States, 94115
      • UCSF Medical Center-Mount Zion
    • Truckee, California, United States, 96161
      • Gene Upshaw Memorial Tahoe Forest Cancer Center
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Hospital
    • Boulder, Colorado, United States, 80304
      • Rocky Mountain Cancer Centers-Boulder
    • Colorado Springs, Colorado, United States, 80907
      • Penrose-Saint Francis Healthcare
    • Colorado Springs, Colorado, United States, 80909
      • UCHealth Memorial Hospital Central
    • Fort Collins, Colorado, United States, 80524
      • Poudre Valley Hospital
    • Greeley, Colorado, United States, 80631
      • North Colorado Medical Center
    • Loveland, Colorado, United States, 80539
      • McKee Medical Center
  • Connecticut
    • Hartford, Connecticut, United States, 06102
      • Hartford Hospital
    • New Britain, Connecticut, United States, 06050
      • The Hospital of Central Connecticut
  • Delaware
    • Newark, Delaware, United States, 19718
      • Christiana Care Health System-Christiana Hospital
  • Florida
    • Deerfield Beach, Florida, United States, 33442
      • UM Sylvester Comprehensive Cancer Center at Deerfield Beach
    • Hollywood, Florida, United States, 33021
      • Memorial Regional Hospital/Joe DiMaggio Children's Hospital
    • Jacksonville, Florida, United States, 32207
      • Baptist MD Anderson Cancer Center
    • Jacksonville, Florida, United States, 32258
      • Baptist Medical Center South
    • Miami, Florida, United States, 33136
      • University of Miami Miller School of Medicine-Sylvester Cancer Center
    • Orlando, Florida, United States, 32806
      • UF Cancer Center at Orlando Health
    • Palatka, Florida, United States, 32177
      • 21st Century Oncology-Palatka
    • Pembroke Pines, Florida, United States, 33028
      • Memorial Hospital West
    • Saint Augustine, Florida, United States, 32086
      • Integrated Community Oncology Network-Flager Cancer Center
    • Stuart, Florida, United States, 34994
      • Robert and Carol Weissman Cancer Center at Martin Health
    • Tampa, Florida, United States, 33612
      • Moffitt Cancer Center
  • Georgia
    • Atlanta, Georgia, United States, 30308
      • Emory University Hospital Midtown
    • Atlanta, Georgia, United States, 30322
      • Emory University Hospital/Winship Cancer Institute
    • Atlanta, Georgia, United States, 30342
      • Emory Saint Joseph's Hospital
    • Gainesville, Georgia, United States, 30501
      • Northeast Georgia Medical Center-Gainesville
    • Savannah, Georgia, United States, 31405
      • Lewis Cancer and Research Pavilion at Saint Joseph's/Candler
  • Hawaii
    • Honolulu, Hawaii, United States, 96813
      • Queen's Medical Center
    • Honolulu, Hawaii, United States, 96817
      • The Cancer Center of Hawaii-Liliha
  • Idaho
    • Boise, Idaho, United States, 83706
      • Saint Alphonsus Cancer Care Center-Boise
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University
    • Chicago, Illinois, United States, 60637
      • University of Chicago Comprehensive Cancer Center
    • Chicago, Illinois, United States, 60612
      • University of Illinois
    • Decatur, Illinois, United States, 62526
      • Decatur Memorial Hospital
    • Effingham, Illinois, United States, 62401
      • Crossroads Cancer Center
    • Elk Grove Village, Illinois, United States, 60007
      • AMITA Health Alexian Brothers Medical Center
    • Elmhurst, Illinois, United States, 60126
      • Elmhurst Memorial Hospital
    • Hinsdale, Illinois, United States, 60521
      • AMITA Health Cancer Institute and Outpatient Center
    • Maywood, Illinois, United States, 60153
      • Loyola University Medical Center
    • Naperville, Illinois, United States, 60540
      • Edward Hospital/Cancer Center
    • Plainfield, Illinois, United States, 60585
      • Edward Hospital/Cancer Center?Plainfield
    • Rockford, Illinois, United States, 61114
      • SwedishAmerican Regional Cancer Center/ACT
    • Springfield, Illinois, United States, 62781
      • Memorial Medical Center
  • Indiana
    • Anderson, Indiana, United States, 46016
      • Saint Vincent Anderson Regional Hospital/Cancer Center
    • Fort Wayne, Indiana, United States, 46805
      • Parkview Hospital Randallia
    • Fort Wayne, Indiana, United States, 46804
      • Radiation Oncology Associates PC
  • Iowa
    • Ames, Iowa, United States, 50010
      • McFarland Clinic PC - Ames
    • Cedar Rapids, Iowa, United States, 52403
      • Mercy Hospital
    • Cedar Rapids, Iowa, United States, 52402
      • Saint Luke's Hospital
    • Sioux City, Iowa, United States, 51101
      • Siouxland Regional Cancer Center
  • Maine
    • Augusta, Maine, United States, 04330
      • Harold Alfond Center for Cancer Care
    • Scarborough, Maine, United States, 04074
      • Maine Medical Center- Scarborough Campus
  • Maryland
    • Baltimore, Maryland, United States, 21215
      • Sinai Hospital of Baltimore
    • Baltimore, Maryland, United States, 21201
      • University of Maryland/Greenebaum Cancer Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Beth Israel Deaconess Medical Center
    • Boston, Massachusetts, United States, 02215
      • Dana-Farber Cancer Institute
    • Boston, Massachusetts, United States, 02111
      • Tufts Medical Center
    • Burlington, Massachusetts, United States, 01805
      • Lahey Hospital and Medical Center
    • Lowell, Massachusetts, United States, 01854
      • Lowell General Hospital
  • Michigan
    • Ann Arbor, Michigan, United States, 48106
      • Saint Joseph Mercy Hospital
    • Dearborn, Michigan, United States, 48124
      • Beaumont Hospital-Dearborn
    • Grand Rapids, Michigan, United States, 49503
      • Spectrum Health at Butterworth Campus
    • Grand Rapids, Michigan, United States, 49503
      • Mercy Health Saint Mary's
    • Kalamazoo, Michigan, United States, 49007
      • West Michigan Cancer Center
    • Livonia, Michigan, United States, 48154
      • Saint Mary Mercy Hospital
    • Pontiac, Michigan, United States, 48341
      • Saint Joseph Mercy Oakland
    • Saginaw, Michigan, United States, 48601
      • Saint Mary's of Michigan
  • Minnesota
    • Coon Rapids, Minnesota, United States, 55433
      • Mercy Hospital
    • Duluth, Minnesota, United States, 55805
      • Miller-Dwan Hospital
    • Fridley, Minnesota, United States, 55432
      • Unity Hospital
    • Minneapolis, Minnesota, United States, 55415
      • Hennepin County Medical Center
    • Minneapolis, Minnesota, United States, 55407
      • Abbott-Northwestern Hospital
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
    • Saint Louis Park, Minnesota, United States, 55416
      • Park Nicollet Clinic - Saint Louis Park
    • Saint Paul, Minnesota, United States, 55101
      • Regions Hospital
    • Saint Paul, Minnesota, United States, 55102
      • United Hospital
    • Willmar, Minnesota, United States, 56201
      • Rice Memorial Hospital
  • Missouri
    • Cape Girardeau, Missouri, United States, 63703
      • Southeast Cancer Center
    • Creve Coeur, Missouri, United States, 63141
      • Siteman Cancer Center at West County Hospital
    • Kansas City, Missouri, United States, 64111
      • Saint Luke's Hospital of Kansas City
    • Rolla, Missouri, United States, 65401
      • Delbert Day Cancer Institute at PCRMC
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine
    • Saint Louis, Missouri, United States, 63131
      • Missouri Baptist Medical Center
    • Saint Louis, Missouri, United States, 63141
      • Mercy Hospital Saint Louis
    • Springfield, Missouri, United States, 65807
      • CoxHealth South Hospital
  • Nebraska
    • Omaha, Nebraska, United States, 68114
      • Nebraska Methodist Hospital
  • New Hampshire
    • Concord, New Hampshire, United States, 03301
      • Concord Hospital
    • Manchester, New Hampshire, United States, 03103
      • Elliot Hospital
  • New Jersey
    • Mount Holly, New Jersey, United States, 08060
      • Virtua Memorial
    • New Brunswick, New Jersey, United States, 08903
      • Rutgers Cancer Institute of New Jersey
    • New Brunswick, New Jersey, United States, 08903
      • Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital
    • Toms River, New Jersey, United States, 08755
      • Community Medical Center
    • Voorhees, New Jersey, United States, 08043
      • Virtua Voorhees
  • New Mexico
    • Albuquerque, New Mexico, United States, 87102
      • University of New Mexico Cancer Center
  • New York
    • Cooperstown, New York, United States, 13326
      • Mary Imogene Bassett Hospital
    • New York, New York, United States, 10065
      • Weill Medical College of Cornell University
    • New York, New York, United States, 10029
      • Mount Sinai Hospital
    • New York, New York, United States, 10003
      • Mount Sinai Union Square
    • Rochester, New York, United States, 14642
      • University of Rochester
    • Staten Island, New York, United States, 10305
      • Staten Island University Hospital
    • Syracuse, New York, United States, 13210
      • State University of New York Upstate Medical University
  • North Carolina
    • Asheville, North Carolina, United States, 28801
      • Cancer Care of Western North Carolina
    • Asheville, North Carolina, United States, 28801
      • Mission Hospital-Memorial Campus
    • Pinehurst, North Carolina, United States, 28374
      • FirstHealth of the Carolinas-Moore Regional Hospital
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest University Health Sciences
  • Ohio
    • Akron, Ohio, United States, 44307
      • Cleveland Clinic Akron General
    • Akron, Ohio, United States, 44304
      • Summa Akron City Hospital/Cooper Cancer Center
    • Barberton, Ohio, United States, 44203
      • Summa Barberton Hospital
    • Chillicothe, Ohio, United States, 45601
      • Adena Regional Medical Center
    • Cleveland, Ohio, United States, 44106
      • Case Western Reserve University
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Foundation
    • Cleveland, Ohio, United States, 44111
      • Cleveland Clinic Cancer Center/Fairview Hospital
    • Columbus, Ohio, United States, 43210
      • Ohio State University Comprehensive Cancer Center
    • Columbus, Ohio, United States, 43219
      • The Mark H Zangmeister Center
    • Columbus, Ohio, United States, 43215
      • Grant Medical Center
    • Elyria, Ohio, United States, 44035
      • Mercy Cancer Center-Elyria
    • Independence, Ohio, United States, 44131
      • Cleveland Clinic Cancer Center Independence
    • Sandusky, Ohio, United States, 44870
      • North Coast Cancer Care
    • Strongsville, Ohio, United States, 44136
      • Cleveland Clinic Cancer Center Strongsville
    • Wooster, Ohio, United States, 44691
      • Cleveland Clinic Wooster Family Health and Surgery Center
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • University of Oklahoma Health Sciences Center
    • Tulsa, Oklahoma, United States, 74136
      • Natalie Warren Bryant Cancer Center at Saint Francis
  • Oregon
    • Clackamas, Oregon, United States, 97015
      • Clackamas Radiation Oncology Center
    • Gresham, Oregon, United States, 97030
      • Legacy Mount Hood Medical Center
    • Portland, Oregon, United States, 97210
      • Legacy Good Samaritan Hospital and Medical Center
    • Portland, Oregon, United States, 97213
      • Providence Portland Medical Center
    • Portland, Oregon, United States, 97225
      • Providence Saint Vincent Medical Center
    • Portland, Oregon, United States, 97227
      • Kaiser Permanente Northwest
    • Salem, Oregon, United States, 97301
      • Salem Hospital
  • Pennsylvania
    • Bryn Mawr, Pennsylvania, United States, 19010
      • Bryn Mawr Hospital
    • Danville, Pennsylvania, United States, 17822
      • Geisinger Medical Center
    • Paoli, Pennsylvania, United States, 19301
      • Paoli Memorial Hospital
    • Philadelphia, Pennsylvania, United States, 19111
      • Fox Chase Cancer Center
    • Sayre, Pennsylvania, United States, 18840
      • Guthrie Medical Group PC-Robert Packer Hospital
    • Wynnewood, Pennsylvania, United States, 19096
      • Lankenau Medical Center
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina
    • Greenville, South Carolina, United States, 29605
      • Greenville Health System Cancer Institute-Faris
    • Greenville, South Carolina, United States, 29615
      • Greenville Health System Cancer Institute-Eastside
    • Greenwood, South Carolina, United States, 29646
      • Self Regional Healthcare
    • Greer, South Carolina, United States, 29651
      • Gibbs Cancer Center-Pelham
    • Greer, South Carolina, United States, 29650
      • Greenville Health System Cancer Institute-Greer
    • Seneca, South Carolina, United States, 29672
      • Greenville Health System Cancer Institute-Seneca
    • Spartanburg, South Carolina, United States, 29303
      • Spartanburg Medical Center
    • Spartanburg, South Carolina, United States, 29307
      • Greenville Health System Cancer Institute-Spartanburg
  • Texas
    • Amarillo, Texas, United States, 79106
      • The Don and Sybil Harrington Cancer Center
    • Dallas, Texas, United States, 75390
      • UT Southwestern/Simmons Cancer Center-Dallas
    • Houston, Texas, United States, 77030
      • M D Anderson Cancer Center
    • Lubbock, Texas, United States, 79410
      • Covenant Medical Center-Lakeside
  • Utah
    • Murray, Utah, United States, 84107
      • Intermountain Medical Center
    • Saint George, Utah, United States, 84770
      • Dixie Medical Center Regional Cancer Center
  • Washington
    • Longview, Washington, United States, 98632
      • PeaceHealth Saint John Medical Center
    • Vancouver, Washington, United States, 98664
      • PeaceHealth Southwest Medical Center
  • West Virginia
    • Huntington, West Virginia, United States, 25701
      • Edwards Comprehensive Cancer Center
  • Wisconsin
    • Green Bay, Wisconsin, United States, 54301
      • Saint Vincent Hospital Cancer Center Green Bay
    • Green Bay, Wisconsin, United States, 54303
      • Saint Vincent Hospital Cancer Center at Saint Mary's
    • Menomonee Falls, Wisconsin, United States, 53051
      • Community Memorial Hospital
    • Mequon, Wisconsin, United States, 53097
      • Columbia Saint Mary's Hospital - Ozaukee
    • Milwaukee, Wisconsin, United States, 53226
      • Froedtert and the Medical College of Wisconsin
    • Milwaukee, Wisconsin, United States, 53211
      • Columbia Saint Mary's Water Tower Medical Commons
    • New Richmond, Wisconsin, United States, 54017
      • Cancer Center of Western Wisconsin
    • Waukesha, Wisconsin, United States, 53188
      • ProHealth Waukesha Memorial Hospital
    • West Bend, Wisconsin, United States, 53095
      • The Alyce and Elmore Kraemer Cancer Care Center

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:

• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: EGFR: Erlotinib; Induction erlotinib for 12 weeks followed by chemotherapy (either cisplatin/etoposide or paclitaxel/carboplatin) and radiation therapy. Patients who have had no response (partial or complete) after 6 weeks of induction therapy start chemoradiation therapy immediately.	Radiation: Radiation Therapy; 30 once-daily 2 Gy fractions over 6 weeks totaling 60 Gy of intensity-modulated radiation therapy (IMRT) or 3-dimensional conformal radiation therapy (3D-CRT).; Other Names: 3-dimensional conformal radiation therapy; 3-dimensional radiation therapy; 3D CONFORMAL RADIATION THERAPY; 3D CRT; 3D-CRT; Conformal Therapy; Radiation Conformal Therapy; IMRT; Intensity-modulated radiation therapy; Drug: Carboplatin; Concurrent: AUC=2, IV, days 1, 8, 14, 22, 29, and 36 of radiation therapy. For patients receiving either erlotinib or crizotinib, carboplatin will begin 2 weeks after erlotinib or crizotinib, as applicable. Consolidation: 4-6 weeks after completion of RT, AUC=6, IV, days 1 and 22.; Other Names: Blastocarb; Carboplat; Carboplatin Hexal; Carboplatino; Carbosin; Carbosol; Carbotec; CBDCA; Displata; Ercar; JM-8; Nealorin; Novoplatinum; Paraplatin; Paraplatin AQ; Paraplatine; Platinwas; Ribocarbo; Drug: Cisplatin; 50 mg/m2, IV (intravenous), on days 1 and 8 of two 4-week cycles concurrent with radiation therapy. For patients receiving either erlotinib or crizotinib, cisplatin will begin 2 weeks after the completion of erlotinib or crizotinib, as applicable.; Other Names: CDDP; Cis-diamminedichloridoplatinum; Cismaplat; Cisplatinum; Neoplatin; Platinol; Abiplatin; Blastolem; Briplatin; Cis-diammine-dichloroplatinum; Cis-diamminedichloro Platinum (II); Cis-diamminedichloroplatinum; Cis-dichloroammine Platinum (II); Cis-platinous Diamine Dichloride; Cis-platinum; Cis-platinum II; Cis-platinum II Diamine Dichloride; Cisplatina; Cisplatyl; Citoplatino; Citosin; Cysplatyna; DDP; Lederplatin; Metaplatin; Peyrone's Chloride; Peyrone's Salt; Placis; Plastistil; Platamine; Platiblastin; Platiblastin-S; Platinex; Platinol- AQ; Platinol-AQ; Platinol-AQ VHA Plus; Platinoxan; Platinum; Platinum Diamminodichloride; Platiran; Platistin; Platosin; Drug: Erlotinib; 150 mg, orally, once daily for four 3-week cycles (12 weeks in total); Other Names: Cp-358,774; Tarceva; OSI-774; Erlotinib Hydrochloride; Drug: Etoposide; 50 mg/m2, IV, on days 1 and 8 of two 4-week cycles concurrent with radiation therapy. For patients receiving either erlotinib or crizotinib, etoposide will begin 2 weeks after the completion of erlotinib or crizotinib, as applicable.; Other Names: Demethyl Epipodophyllotoxin Ethylidine Glucoside; EPEG; Lastet; Toposar; Vepesid; VP 16-213; VP-16; VP-16-213; Drug: Paclitaxel; Concurrent: 45 mg/m2, IV, days 1, 8, 14, 22, 29, and 36 of radiation therapy. For patients receiving either erlotinib or crizotinib, carboplatin will begin 2 weeks after erlotinib or crizotinib, as applicable. Consolidation: 4-6 weeks after completion of RT, 200 mg/m2, IV, days 1 and 22.; Other Names: Taxol; Anzatax; Asotax; Bristaxol; Praxel; Taxol Konzentrat
Active Comparator: EGFR: No Erlotinib; Chemotherapy (either cisplatin/etoposide or paclitaxel/carboplatin) and radiation therapy.	Radiation: Radiation Therapy; 30 once-daily 2 Gy fractions over 6 weeks totaling 60 Gy of intensity-modulated radiation therapy (IMRT) or 3-dimensional conformal radiation therapy (3D-CRT).; Other Names: 3-dimensional conformal radiation therapy; 3-dimensional radiation therapy; 3D CONFORMAL RADIATION THERAPY; 3D CRT; 3D-CRT; Conformal Therapy; Radiation Conformal Therapy; IMRT; Intensity-modulated radiation therapy; Drug: Carboplatin; Concurrent: AUC=2, IV, days 1, 8, 14, 22, 29, and 36 of radiation therapy. For patients receiving either erlotinib or crizotinib, carboplatin will begin 2 weeks after erlotinib or crizotinib, as applicable. Consolidation: 4-6 weeks after completion of RT, AUC=6, IV, days 1 and 22.; Other Names: Blastocarb; Carboplat; Carboplatin Hexal; Carboplatino; Carbosin; Carbosol; Carbotec; CBDCA; Displata; Ercar; JM-8; Nealorin; Novoplatinum; Paraplatin; Paraplatin AQ; Paraplatine; Platinwas; Ribocarbo; Drug: Cisplatin; 50 mg/m2, IV (intravenous), on days 1 and 8 of two 4-week cycles concurrent with radiation therapy. For patients receiving either erlotinib or crizotinib, cisplatin will begin 2 weeks after the completion of erlotinib or crizotinib, as applicable.; Other Names: CDDP; Cis-diamminedichloridoplatinum; Cismaplat; Cisplatinum; Neoplatin; Platinol; Abiplatin; Blastolem; Briplatin; Cis-diammine-dichloroplatinum; Cis-diamminedichloro Platinum (II); Cis-diamminedichloroplatinum; Cis-dichloroammine Platinum (II); Cis-platinous Diamine Dichloride; Cis-platinum; Cis-platinum II; Cis-platinum II Diamine Dichloride; Cisplatina; Cisplatyl; Citoplatino; Citosin; Cysplatyna; DDP; Lederplatin; Metaplatin; Peyrone's Chloride; Peyrone's Salt; Placis; Plastistil; Platamine; Platiblastin; Platiblastin-S; Platinex; Platinol- AQ; Platinol-AQ; Platinol-AQ VHA Plus; Platinoxan; Platinum; Platinum Diamminodichloride; Platiran; Platistin; Platosin; Drug: Etoposide; 50 mg/m2, IV, on days 1 and 8 of two 4-week cycles concurrent with radiation therapy. For patients receiving either erlotinib or crizotinib, etoposide will begin 2 weeks after the completion of erlotinib or crizotinib, as applicable.; Other Names: Demethyl Epipodophyllotoxin Ethylidine Glucoside; EPEG; Lastet; Toposar; Vepesid; VP 16-213; VP-16; VP-16-213; Drug: Paclitaxel; Concurrent: 45 mg/m2, IV, days 1, 8, 14, 22, 29, and 36 of radiation therapy. For patients receiving either erlotinib or crizotinib, carboplatin will begin 2 weeks after erlotinib or crizotinib, as applicable. Consolidation: 4-6 weeks after completion of RT, 200 mg/m2, IV, days 1 and 22.; Other Names: Taxol; Anzatax; Asotax; Bristaxol; Praxel; Taxol Konzentrat
Experimental: ALK: Crizotinib; Induction crizotinib for 12 weeks followed by chemotherapy (either cisplatin/etoposide or paclitaxel/carboplatin) and radiation therapy. Patients who have had no response (partial or complete) after 6 weeks of induction therapy start chemoradiation therapy immediately.	Radiation: Radiation Therapy; 30 once-daily 2 Gy fractions over 6 weeks totaling 60 Gy of intensity-modulated radiation therapy (IMRT) or 3-dimensional conformal radiation therapy (3D-CRT).; Other Names: 3-dimensional conformal radiation therapy; 3-dimensional radiation therapy; 3D CONFORMAL RADIATION THERAPY; 3D CRT; 3D-CRT; Conformal Therapy; Radiation Conformal Therapy; IMRT; Intensity-modulated radiation therapy; Drug: Carboplatin; Concurrent: AUC=2, IV, days 1, 8, 14, 22, 29, and 36 of radiation therapy. For patients receiving either erlotinib or crizotinib, carboplatin will begin 2 weeks after erlotinib or crizotinib, as applicable. Consolidation: 4-6 weeks after completion of RT, AUC=6, IV, days 1 and 22.; Other Names: Blastocarb; Carboplat; Carboplatin Hexal; Carboplatino; Carbosin; Carbosol; Carbotec; CBDCA; Displata; Ercar; JM-8; Nealorin; Novoplatinum; Paraplatin; Paraplatin AQ; Paraplatine; Platinwas; Ribocarbo; Drug: Cisplatin; 50 mg/m2, IV (intravenous), on days 1 and 8 of two 4-week cycles concurrent with radiation therapy. For patients receiving either erlotinib or crizotinib, cisplatin will begin 2 weeks after the completion of erlotinib or crizotinib, as applicable.; Other Names: CDDP; Cis-diamminedichloridoplatinum; Cismaplat; Cisplatinum; Neoplatin; Platinol; Abiplatin; Blastolem; Briplatin; Cis-diammine-dichloroplatinum; Cis-diamminedichloro Platinum (II); Cis-diamminedichloroplatinum; Cis-dichloroammine Platinum (II); Cis-platinous Diamine Dichloride; Cis-platinum; Cis-platinum II; Cis-platinum II Diamine Dichloride; Cisplatina; Cisplatyl; Citoplatino; Citosin; Cysplatyna; DDP; Lederplatin; Metaplatin; Peyrone's Chloride; Peyrone's Salt; Placis; Plastistil; Platamine; Platiblastin; Platiblastin-S; Platinex; Platinol- AQ; Platinol-AQ; Platinol-AQ VHA Plus; Platinoxan; Platinum; Platinum Diamminodichloride; Platiran; Platistin; Platosin; Drug: Etoposide; 50 mg/m2, IV, on days 1 and 8 of two 4-week cycles concurrent with radiation therapy. For patients receiving either erlotinib or crizotinib, etoposide will begin 2 weeks after the completion of erlotinib or crizotinib, as applicable.; Other Names: Demethyl Epipodophyllotoxin Ethylidine Glucoside; EPEG; Lastet; Toposar; Vepesid; VP 16-213; VP-16; VP-16-213; Drug: Paclitaxel; Concurrent: 45 mg/m2, IV, days 1, 8, 14, 22, 29, and 36 of radiation therapy. For patients receiving either erlotinib or crizotinib, carboplatin will begin 2 weeks after erlotinib or crizotinib, as applicable. Consolidation: 4-6 weeks after completion of RT, 200 mg/m2, IV, days 1 and 22.; Other Names: Taxol; Anzatax; Asotax; Bristaxol; Praxel; Taxol Konzentrat; Drug: Crizotinib; 250 mg, orally, twice daily for four 3-week cycles (12 weeks in total); Other Names: MET Tyrosine Kinase Inhibitor PF-02341066; PF-02341066; PF-2341066; Xalkori
Active Comparator: ALK: No Crizotinib; Chemotherapy (either cisplatin/etoposide or paclitaxel/carboplatin) and radiation therapy.	Radiation: Radiation Therapy; 30 once-daily 2 Gy fractions over 6 weeks totaling 60 Gy of intensity-modulated radiation therapy (IMRT) or 3-dimensional conformal radiation therapy (3D-CRT).; Other Names: 3-dimensional conformal radiation therapy; 3-dimensional radiation therapy; 3D CONFORMAL RADIATION THERAPY; 3D CRT; 3D-CRT; Conformal Therapy; Radiation Conformal Therapy; IMRT; Intensity-modulated radiation therapy; Drug: Carboplatin; Concurrent: AUC=2, IV, days 1, 8, 14, 22, 29, and 36 of radiation therapy. For patients receiving either erlotinib or crizotinib, carboplatin will begin 2 weeks after erlotinib or crizotinib, as applicable. Consolidation: 4-6 weeks after completion of RT, AUC=6, IV, days 1 and 22.; Other Names: Blastocarb; Carboplat; Carboplatin Hexal; Carboplatino; Carbosin; Carbosol; Carbotec; CBDCA; Displata; Ercar; JM-8; Nealorin; Novoplatinum; Paraplatin; Paraplatin AQ; Paraplatine; Platinwas; Ribocarbo; Drug: Cisplatin; 50 mg/m2, IV (intravenous), on days 1 and 8 of two 4-week cycles concurrent with radiation therapy. For patients receiving either erlotinib or crizotinib, cisplatin will begin 2 weeks after the completion of erlotinib or crizotinib, as applicable.; Other Names: CDDP; Cis-diamminedichloridoplatinum; Cismaplat; Cisplatinum; Neoplatin; Platinol; Abiplatin; Blastolem; Briplatin; Cis-diammine-dichloroplatinum; Cis-diamminedichloro Platinum (II); Cis-diamminedichloroplatinum; Cis-dichloroammine Platinum (II); Cis-platinous Diamine Dichloride; Cis-platinum; Cis-platinum II; Cis-platinum II Diamine Dichloride; Cisplatina; Cisplatyl; Citoplatino; Citosin; Cysplatyna; DDP; Lederplatin; Metaplatin; Peyrone's Chloride; Peyrone's Salt; Placis; Plastistil; Platamine; Platiblastin; Platiblastin-S; Platinex; Platinol- AQ; Platinol-AQ; Platinol-AQ VHA Plus; Platinoxan; Platinum; Platinum Diamminodichloride; Platiran; Platistin; Platosin; Drug: Etoposide; 50 mg/m2, IV, on days 1 and 8 of two 4-week cycles concurrent with radiation therapy. For patients receiving either erlotinib or crizotinib, etoposide will begin 2 weeks after the completion of erlotinib or crizotinib, as applicable.; Other Names: Demethyl Epipodophyllotoxin Ethylidine Glucoside; EPEG; Lastet; Toposar; Vepesid; VP 16-213; VP-16; VP-16-213; Drug: Paclitaxel; Concurrent: 45 mg/m2, IV, days 1, 8, 14, 22, 29, and 36 of radiation therapy. For patients receiving either erlotinib or crizotinib, carboplatin will begin 2 weeks after erlotinib or crizotinib, as applicable. Consolidation: 4-6 weeks after completion of RT, 200 mg/m2, IV, days 1 and 22.; Other Names: Taxol; Anzatax; Asotax; Bristaxol; Praxel; Taxol Konzentrat

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free Survival	Progression is defined using the Response Evaluation Criteria In Solid Tumors Criteria (RECIST) guideline v1.1 as a 20% increase in the sum of the longest diameter of target lesions, a measurable increase in a non-target lesion, or the appearance of new lesions at any location. Progression-free survival time is measured from the date of randomization to the date of first progression, death, or last known follow-up (censored). No statistical testing was done due to early study termination.	From randomization to study termination. Maximum follow-up was 39.0 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Patients With Complete or Partial Response	Per the RECIST guideline v1.1 complete response is defined as the disappearance of all target lesions; any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. Partial response is defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. No statistical testing was done due to early study termination.	From randomization to study termination. Maximum follow-up was 39.0 months
Number of Patients With Grade 3-5 Adverse Events	Adverse events (AE) are graded using the Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Grade refers to the severity of the AE. The CTCAE v4.0 assigns Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1 Mild AE, Grade 2 Moderate AE, Grade 3 Severe AE, Grade 4 Life-threatening or disabling AE, Grade 5 Death related to AE.	From randomization to study termination. Maximum follow-up was 39.0 months
Overall Survival	Overall survival time is defined as time from randomization to the date of death from any cause. Overall survival rates are estimated by the Kaplan-Meier method. Patients last known to be alive are censored at the date of last contact.	From randomization to study termination. Maximum follow-up was 39.0 months
Local-regional Progression-free Survival	Progression is defined using the RECIST guideline v1.1 as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new regional lesions. Local progression is defined as progression within the planning target volume (PTV). Regional progression is defined as progression outside of the PTV but within the same lobe of the lung as the primary tumor or in regional lymph nodes as defined by the American Joint Committee on Cancer (AJCC) 7th edition nodal stations. Local-regional progression-free survival time is measured from the date of randomization to the date of first local-regional progression, death, or last known follow-up (censored). Local-regional progression-free survival rates are estimated using the Kaplan-Meier method. No testing was done due to early study termination.	From randomization to study termination. Maximum follow-up was 39.0 months
Distant Progression-free Survival	Distant progression is defined as the first occurrence of distant metastasis. Distant progression-free survival time is measured from the date of randomization to the date of first distant progression, death, or last known follow-up (censored). Distant progression-free survival rates are estimated using the Kaplan-Meier method. No testing was done due to early study termination.	From randomization to study termination. Maximum follow-up was 39.0 months
Correlation Between Clinical Outcomes and Tumor Molecular Aberrations		Baseline

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)
• Collaborators: NRG Oncology
• Investigators: Principal Investigator: Ramaswamy Govindan, NRG Oncology

Study record dates

Study Major Dates

• Study Start (Actual): November 4, 2013
• Primary Completion (Actual): June 4, 2018
• Study Completion (Actual): June 4, 2018

Study Registration Dates

• First Submitted: April 1, 2013
• First Submitted That Met QC Criteria: April 1, 2013
• First Posted (Estimate): April 2, 2013

Study Record Updates

• Last Update Posted (Actual): August 5, 2019
• Last Update Submitted That Met QC Criteria: August 2, 2019
• Last Verified: June 1, 2019

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; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Dermatologic Agents; Protein Kinase Inhibitors; Keratolytic Agents; Carboplatin; Etoposide; Etoposide phosphate; Paclitaxel; Erlotinib Hydrochloride; Cisplatin; Podophyllotoxin; Albumin-Bound Paclitaxel; Crizotinib
• Other Study ID Numbers: NCI-2013-00737 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); U10CA180868 (U.S. NIH Grant/Contract); U10CA021661 (U.S. NIH Grant/Contract); RTOG-1306 (Other Identifier: CTEP)