Back to results

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

Primary Purpose

Stage III Non-Small Cell Lung Cancer AJCC v7, Stage IIIA Non-Small Cell Lung Cancer AJCC v7, Stage IIIB Non-Small Cell Lung Cancer AJCC v7

Status

Terminated

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Radiation Therapy

Carboplatin

Cisplatin

Crizotinib

Erlotinib

Etoposide

Paclitaxel

About this trial

This is an interventional treatment trial for Stage III Non-Small Cell Lung Cancer AJCC v7

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

University of Alabama at Birmingham Cancer Center
Providence Alaska Medical Center
Banner MD Anderson Cancer Center
Mayo Clinic in Arizona
AIS Cancer Center at San Joaquin Community Hospital
UC San Diego Moores Cancer Center
Fremont - Rideout Cancer Center
Mercy UC Davis Cancer Center
Stanford Cancer Institute Palo Alto
University of California Davis Comprehensive Cancer Center
Saint Helena Hospital
UCSF Medical Center-Mount Zion
Gene Upshaw Memorial Tahoe Forest Cancer Center
University of Colorado Hospital
Rocky Mountain Cancer Centers-Boulder
Penrose-Saint Francis Healthcare
UCHealth Memorial Hospital Central
Poudre Valley Hospital
North Colorado Medical Center
McKee Medical Center
Hartford Hospital
The Hospital of Central Connecticut
Christiana Care Health System-Christiana Hospital
UM Sylvester Comprehensive Cancer Center at Deerfield Beach
Memorial Regional Hospital/Joe DiMaggio Children's Hospital
Baptist MD Anderson Cancer Center
Baptist Medical Center South
University of Miami Miller School of Medicine-Sylvester Cancer Center
UF Cancer Center at Orlando Health
21st Century Oncology-Palatka
Memorial Hospital West
Integrated Community Oncology Network-Flager Cancer Center
Robert and Carol Weissman Cancer Center at Martin Health
Moffitt Cancer Center
Emory University Hospital Midtown
Emory University Hospital/Winship Cancer Institute
Emory Saint Joseph's Hospital
Northeast Georgia Medical Center-Gainesville
Lewis Cancer and Research Pavilion at Saint Joseph's/Candler
Queen's Medical Center
The Cancer Center of Hawaii-Liliha
Saint Alphonsus Cancer Care Center-Boise
Northwestern University
University of Illinois
University of Chicago Comprehensive Cancer Center
Decatur Memorial Hospital
Crossroads Cancer Center
AMITA Health Alexian Brothers Medical Center
Elmhurst Memorial Hospital
AMITA Health Cancer Institute and Outpatient Center
Loyola University Medical Center
Edward Hospital/Cancer Center
Edward Hospital/Cancer Center?Plainfield
SwedishAmerican Regional Cancer Center/ACT
Memorial Medical Center
Saint Vincent Anderson Regional Hospital/Cancer Center
Radiation Oncology Associates PC
Parkview Hospital Randallia
McFarland Clinic PC - Ames
Saint Luke's Hospital
Mercy Hospital
Siouxland Regional Cancer Center
Harold Alfond Center for Cancer Care
Maine Medical Center- Scarborough Campus
University of Maryland/Greenebaum Cancer Center
Sinai Hospital of Baltimore
Tufts Medical Center
Beth Israel Deaconess Medical Center
Dana-Farber Cancer Institute
Lahey Hospital and Medical Center
Lowell General Hospital
Saint Joseph Mercy Hospital
Beaumont Hospital-Dearborn
Mercy Health Saint Mary's
Spectrum Health at Butterworth Campus
West Michigan Cancer Center
Saint Mary Mercy Hospital
Saint Joseph Mercy Oakland
Saint Mary's of Michigan
Mercy Hospital
Miller-Dwan Hospital
Unity Hospital
Abbott-Northwestern Hospital
Hennepin County Medical Center
Mayo Clinic
Park Nicollet Clinic - Saint Louis Park
Regions Hospital
United Hospital
Rice Memorial Hospital
Southeast Cancer Center
Siteman Cancer Center at West County Hospital
Saint Luke's Hospital of Kansas City
Delbert Day Cancer Institute at PCRMC
Washington University School of Medicine
Missouri Baptist Medical Center
Mercy Hospital Saint Louis
CoxHealth South Hospital
Nebraska Methodist Hospital
Concord Hospital
Elliot Hospital
Virtua Memorial
Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital
Rutgers Cancer Institute of New Jersey
Community Medical Center
Virtua Voorhees
University of New Mexico Cancer Center
Mary Imogene Bassett Hospital
Mount Sinai Union Square
Mount Sinai Hospital
Weill Medical College of Cornell University
University of Rochester
Staten Island University Hospital
State University of New York Upstate Medical University
Cancer Care of Western North Carolina
Mission Hospital-Memorial Campus
FirstHealth of the Carolinas-Moore Regional Hospital
Wake Forest University Health Sciences
Summa Akron City Hospital/Cooper Cancer Center
Cleveland Clinic Akron General
Summa Barberton Hospital
Adena Regional Medical Center
Case Western Reserve University
Cleveland Clinic Cancer Center/Fairview Hospital
Cleveland Clinic Foundation
Ohio State University Comprehensive Cancer Center
Grant Medical Center
The Mark H Zangmeister Center
Mercy Cancer Center-Elyria
Cleveland Clinic Cancer Center Independence
North Coast Cancer Care
Cleveland Clinic Cancer Center Strongsville
Cleveland Clinic Wooster Family Health and Surgery Center
University of Oklahoma Health Sciences Center
Natalie Warren Bryant Cancer Center at Saint Francis
Clackamas Radiation Oncology Center
Legacy Mount Hood Medical Center
Legacy Good Samaritan Hospital and Medical Center
Providence Portland Medical Center
Providence Saint Vincent Medical Center
Kaiser Permanente Northwest
Salem Hospital
Bryn Mawr Hospital
Geisinger Medical Center
Paoli Memorial Hospital
Fox Chase Cancer Center
Guthrie Medical Group PC-Robert Packer Hospital
Lankenau Medical Center
Medical University of South Carolina
Greenville Health System Cancer Institute-Faris
Greenville Health System Cancer Institute-Eastside
Self Regional Healthcare
Greenville Health System Cancer Institute-Greer
Gibbs Cancer Center-Pelham
Greenville Health System Cancer Institute-Seneca
Spartanburg Medical Center
Greenville Health System Cancer Institute-Spartanburg
The Don and Sybil Harrington Cancer Center
UT Southwestern/Simmons Cancer Center-Dallas
M D Anderson Cancer Center
Covenant Medical Center-Lakeside
Intermountain Medical Center
Dixie Medical Center Regional Cancer Center
PeaceHealth Saint John Medical Center
PeaceHealth Southwest Medical Center
Edwards Comprehensive Cancer Center
Saint Vincent Hospital Cancer Center Green Bay
Saint Vincent Hospital Cancer Center at Saint Mary's
Community Memorial Hospital
Columbia Saint Mary's Hospital - Ozaukee
Columbia Saint Mary's Water Tower Medical Commons
Froedtert and the Medical College of Wisconsin
Cancer Center of Western Wisconsin
ProHealth Waukesha Memorial Hospital
The Alyce and Elmore Kraemer Cancer Care Center

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Active Comparator

Experimental

Active Comparator

Arm Label

EGFR: Erlotinib

EGFR: No Erlotinib

ALK: Crizotinib

ALK: No Crizotinib

Arm Description

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.

Chemotherapy (either cisplatin/etoposide or paclitaxel/carboplatin) and radiation therapy.

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.

Chemotherapy (either cisplatin/etoposide or paclitaxel/carboplatin) and radiation therapy.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.

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.

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.

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.

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.

Correlation Between Clinical Outcomes and Tumor Molecular Aberrations

Full Information

NCT ID

NCT01822496

First Posted

April 1, 2013

Last Updated

August 2, 2019

Sponsor

National Cancer Institute (NCI)

Collaborators

NRG Oncology

1. Study Identification

Unique Protocol Identification Number

NCT01822496

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)

Study Type

Interventional

2. Study Status

Record Verification Date

June 2019

Overall Recruitment Status

Terminated

Study Start Date

November 4, 2013 (Actual)

Primary Completion Date

June 4, 2018 (Actual)

Study Completion Date

June 4, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

National Cancer Institute (NCI)

Collaborators

NRG Oncology

4. Oversight

Data Monitoring Committee

5. Study Description

Brief Summary

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: 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Stage III Non-Small Cell Lung Cancer AJCC v7, Stage IIIA Non-Small Cell Lung Cancer AJCC v7, Stage IIIB Non-Small Cell Lung Cancer AJCC v7

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

59 (Actual)

8. Arms, Groups, and Interventions

Arm Title

EGFR: Erlotinib

Arm Type

Experimental

Arm Description

Arm Title

EGFR: No Erlotinib

Arm Type

Active Comparator

Arm Description

Chemotherapy (either cisplatin/etoposide or paclitaxel/carboplatin) and radiation therapy.

Arm Title

ALK: Crizotinib

Arm Type

Experimental

Arm Description

Arm Title

ALK: No Crizotinib

Arm Type

Active Comparator

Arm Description

Chemotherapy (either cisplatin/etoposide or paclitaxel/carboplatin) and radiation therapy.

Intervention Type

Radiation

Intervention Name(s)

Radiation Therapy

Other Intervention Name(s)

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

Intervention Description

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).

Intervention Type

Drug

Intervention Name(s)

Carboplatin

Other Intervention Name(s)

Blastocarb, Carboplat, Carboplatin Hexal, Carboplatino, Carbosin, Carbosol, Carbotec, CBDCA, Displata, Ercar, JM-8, Nealorin, Novoplatinum, Paraplatin, Paraplatin AQ, Paraplatine, Platinwas, Ribocarbo

Intervention Description

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.

Intervention Type

Drug

Intervention Name(s)

Cisplatin

Other Intervention Name(s)

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, 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

Intervention Description

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.

Intervention Type

Drug

Intervention Name(s)

Crizotinib

Other Intervention Name(s)

MET Tyrosine Kinase Inhibitor PF-02341066, PF-02341066, PF-2341066, Xalkori

Intervention Description

250 mg, orally, twice daily for four 3-week cycles (12 weeks in total)

Intervention Type

Drug

Intervention Name(s)

Erlotinib

Other Intervention Name(s)

Cp-358,774, Erlotinib Hydrochloride, OSI-774, Tarceva

Intervention Description

150 mg, orally, once daily for four 3-week cycles (12 weeks in total)

Intervention Type

Drug

Intervention Name(s)

Etoposide

Other Intervention Name(s)

Demethyl Epipodophyllotoxin Ethylidine Glucoside, EPEG, Lastet, Toposar, Vepesid, VP 16-213, VP-16, VP-16-213

Intervention Description

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.

Intervention Type

Drug

Intervention Name(s)

Paclitaxel

Other Intervention Name(s)

Anzatax, Asotax, Bristaxol, Praxel, Taxol, Taxol Konzentrat

Intervention Description

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.

Primary Outcome Measure Information:

Title

Progression-free Survival

Description

Time Frame