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

Stage IIIA Non-Small Cell Lung Cancer AJCC v7 Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01822496
• Other study ID #: NCI-2013-00737
• Secondary ID: NCI-2013-00737RT
• Status: Terminated
• Phase: Phase 2
• Start date: November 4, 2013
• Est. completion date: June 4, 2018

Study information

• Verified date: June 2019
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 59
• Est. completion date: June 4, 2018
• Est. primary completion date: June 4, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• 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

Intervention

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).

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.
• 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.
• Crizotinib
250 mg, orally, twice daily for four 3-week cycles (12 weeks in total)
• Erlotinib
150 mg, orally, once daily for four 3-week cycles (12 weeks in total)
• 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.
• 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.

Locations

Country	Name	City	State
United States	Cleveland Clinic Akron General	Akron	Ohio
United States	Summa Akron City Hospital/Cooper Cancer Center	Akron	Ohio
United States	University of New Mexico Cancer Center	Albuquerque	New Mexico
United States	The Don and Sybil Harrington Cancer Center	Amarillo	Texas
United States	McFarland Clinic PC - Ames	Ames	Iowa
United States	Providence Alaska Medical Center	Anchorage	Alaska
United States	Saint Vincent Anderson Regional Hospital/Cancer Center	Anderson	Indiana
United States	Saint Joseph Mercy Hospital	Ann Arbor	Michigan
United States	Cancer Care of Western North Carolina	Asheville	North Carolina
United States	Mission Hospital-Memorial Campus	Asheville	North Carolina
United States	Emory Saint Joseph's Hospital	Atlanta	Georgia
United States	Emory University Hospital Midtown	Atlanta	Georgia
United States	Emory University Hospital/Winship Cancer Institute	Atlanta	Georgia
United States	Harold Alfond Center for Cancer Care	Augusta	Maine
United States	University of Colorado Hospital	Aurora	Colorado
United States	AIS Cancer Center at San Joaquin Community Hospital	Bakersfield	California
United States	Sinai Hospital of Baltimore	Baltimore	Maryland
United States	University of Maryland/Greenebaum Cancer Center	Baltimore	Maryland
United States	Summa Barberton Hospital	Barberton	Ohio
United States	University of Alabama at Birmingham Cancer Center	Birmingham	Alabama
United States	Saint Alphonsus Cancer Care Center-Boise	Boise	Idaho
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	Tufts Medical Center	Boston	Massachusetts
United States	Rocky Mountain Cancer Centers-Boulder	Boulder	Colorado
United States	Bryn Mawr Hospital	Bryn Mawr	Pennsylvania
United States	Lahey Hospital and Medical Center	Burlington	Massachusetts
United States	Southeast Cancer Center	Cape Girardeau	Missouri
United States	Mercy Hospital	Cedar Rapids	Iowa
United States	Saint Luke's Hospital	Cedar Rapids	Iowa
United States	Medical University of South Carolina	Charleston	South Carolina
United States	Northwestern University	Chicago	Illinois
United States	University of Chicago Comprehensive Cancer Center	Chicago	Illinois
United States	University of Illinois	Chicago	Illinois
United States	Adena Regional Medical Center	Chillicothe	Ohio
United States	Clackamas Radiation Oncology Center	Clackamas	Oregon
United States	Case Western Reserve University	Cleveland	Ohio
United States	Cleveland Clinic Cancer Center/Fairview Hospital	Cleveland	Ohio
United States	Cleveland Clinic Foundation	Cleveland	Ohio
United States	Penrose-Saint Francis Healthcare	Colorado Springs	Colorado
United States	UCHealth Memorial Hospital Central	Colorado Springs	Colorado
United States	Grant Medical Center	Columbus	Ohio
United States	Ohio State University Comprehensive Cancer Center	Columbus	Ohio
United States	The Mark H Zangmeister Center	Columbus	Ohio
United States	Concord Hospital	Concord	New Hampshire
United States	Mercy Hospital	Coon Rapids	Minnesota
United States	Mary Imogene Bassett Hospital	Cooperstown	New York
United States	Siteman Cancer Center at West County Hospital	Creve Coeur	Missouri
United States	UT Southwestern/Simmons Cancer Center-Dallas	Dallas	Texas
United States	Geisinger Medical Center	Danville	Pennsylvania
United States	Beaumont Hospital-Dearborn	Dearborn	Michigan
United States	Decatur Memorial Hospital	Decatur	Illinois
United States	UM Sylvester Comprehensive Cancer Center at Deerfield Beach	Deerfield Beach	Florida
United States	Miller-Dwan Hospital	Duluth	Minnesota
United States	Crossroads Cancer Center	Effingham	Illinois
United States	AMITA Health Alexian Brothers Medical Center	Elk Grove Village	Illinois
United States	Elmhurst Memorial Hospital	Elmhurst	Illinois
United States	Mercy Cancer Center-Elyria	Elyria	Ohio
United States	Poudre Valley Hospital	Fort Collins	Colorado
United States	Parkview Hospital Randallia	Fort Wayne	Indiana
United States	Radiation Oncology Associates PC	Fort Wayne	Indiana
United States	Unity Hospital	Fridley	Minnesota
United States	Northeast Georgia Medical Center-Gainesville	Gainesville	Georgia
United States	Banner MD Anderson Cancer Center	Gilbert	Arizona
United States	Mercy Health Saint Mary's	Grand Rapids	Michigan
United States	Spectrum Health at Butterworth Campus	Grand Rapids	Michigan
United States	North Colorado Medical Center	Greeley	Colorado
United States	Saint Vincent Hospital Cancer Center at Saint Mary's	Green Bay	Wisconsin
United States	Saint Vincent Hospital Cancer Center Green Bay	Green Bay	Wisconsin
United States	Greenville Health System Cancer Institute-Eastside	Greenville	South Carolina
United States	Greenville Health System Cancer Institute-Faris	Greenville	South Carolina
United States	Self Regional Healthcare	Greenwood	South Carolina
United States	Gibbs Cancer Center-Pelham	Greer	South Carolina
United States	Greenville Health System Cancer Institute-Greer	Greer	South Carolina
United States	Legacy Mount Hood Medical Center	Gresham	Oregon
United States	Hartford Hospital	Hartford	Connecticut
United States	AMITA Health Cancer Institute and Outpatient Center	Hinsdale	Illinois
United States	Memorial Regional Hospital/Joe DiMaggio Children's Hospital	Hollywood	Florida
United States	Queen's Medical Center	Honolulu	Hawaii
United States	The Cancer Center of Hawaii-Liliha	Honolulu	Hawaii
United States	M D Anderson Cancer Center	Houston	Texas
United States	Edwards Comprehensive Cancer Center	Huntington	West Virginia
United States	Cleveland Clinic Cancer Center Independence	Independence	Ohio
United States	Baptist MD Anderson Cancer Center	Jacksonville	Florida
United States	Baptist Medical Center South	Jacksonville	Florida
United States	West Michigan Cancer Center	Kalamazoo	Michigan
United States	Saint Luke's Hospital of Kansas City	Kansas City	Missouri
United States	UC San Diego Moores Cancer Center	La Jolla	California
United States	Saint Mary Mercy Hospital	Livonia	Michigan
United States	PeaceHealth Saint John Medical Center	Longview	Washington
United States	McKee Medical Center	Loveland	Colorado
United States	Lowell General Hospital	Lowell	Massachusetts
United States	Covenant Medical Center-Lakeside	Lubbock	Texas
United States	Elliot Hospital	Manchester	New Hampshire
United States	Fremont - Rideout Cancer Center	Marysville	California
United States	Loyola University Medical Center	Maywood	Illinois
United States	Community Memorial Hospital	Menomonee Falls	Wisconsin
United States	Columbia Saint Mary's Hospital - Ozaukee	Mequon	Wisconsin
United States	Mercy UC Davis Cancer Center	Merced	California
United States	University of Miami Miller School of Medicine-Sylvester Cancer Center	Miami	Florida
United States	Columbia Saint Mary's Water Tower Medical Commons	Milwaukee	Wisconsin
United States	Froedtert and the Medical College of Wisconsin	Milwaukee	Wisconsin
United States	Abbott-Northwestern Hospital	Minneapolis	Minnesota
United States	Hennepin County Medical Center	Minneapolis	Minnesota
United States	Virtua Memorial	Mount Holly	New Jersey
United States	Intermountain Medical Center	Murray	Utah
United States	Edward Hospital/Cancer Center	Naperville	Illinois
United States	The Hospital of Central Connecticut	New Britain	Connecticut
United States	Rutgers Cancer Institute of New Jersey	New Brunswick	New Jersey
United States	Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital	New Brunswick	New Jersey
United States	Cancer Center of Western Wisconsin	New Richmond	Wisconsin
United States	Mount Sinai Hospital	New York	New York
United States	Mount Sinai Union Square	New York	New York
United States	Weill Medical College of Cornell University	New York	New York
United States	Christiana Care Health System-Christiana Hospital	Newark	Delaware
United States	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma
United States	Nebraska Methodist Hospital	Omaha	Nebraska
United States	UF Cancer Center at Orlando Health	Orlando	Florida
United States	21st Century Oncology-Palatka	Palatka	Florida
United States	Stanford Cancer Institute Palo Alto	Palo Alto	California
United States	Paoli Memorial Hospital	Paoli	Pennsylvania
United States	Memorial Hospital West	Pembroke Pines	Florida
United States	Fox Chase Cancer Center	Philadelphia	Pennsylvania
United States	FirstHealth of the Carolinas-Moore Regional Hospital	Pinehurst	North Carolina
United States	Edward Hospital/Cancer Center?Plainfield	Plainfield	Illinois
United States	Saint Joseph Mercy Oakland	Pontiac	Michigan
United States	Kaiser Permanente Northwest	Portland	Oregon
United States	Legacy Good Samaritan Hospital and Medical Center	Portland	Oregon
United States	Providence Portland Medical Center	Portland	Oregon
United States	Providence Saint Vincent Medical Center	Portland	Oregon
United States	Mayo Clinic	Rochester	Minnesota
United States	University of Rochester	Rochester	New York
United States	SwedishAmerican Regional Cancer Center/ACT	Rockford	Illinois
United States	Delbert Day Cancer Institute at PCRMC	Rolla	Missouri
United States	University of California Davis Comprehensive Cancer Center	Sacramento	California
United States	Saint Mary's of Michigan	Saginaw	Michigan
United States	Integrated Community Oncology Network-Flager Cancer Center	Saint Augustine	Florida
United States	Dixie Medical Center Regional Cancer Center	Saint George	Utah
United States	Saint Helena Hospital	Saint Helena	California
United States	Mercy Hospital Saint Louis	Saint Louis	Missouri
United States	Missouri Baptist Medical Center	Saint Louis	Missouri
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	Park Nicollet Clinic - Saint Louis Park	Saint Louis Park	Minnesota
United States	Regions Hospital	Saint Paul	Minnesota
United States	United Hospital	Saint Paul	Minnesota
United States	Salem Hospital	Salem	Oregon
United States	UCSF Medical Center-Mount Zion	San Francisco	California
United States	North Coast Cancer Care	Sandusky	Ohio
United States	Lewis Cancer and Research Pavilion at Saint Joseph's/Candler	Savannah	Georgia
United States	Guthrie Medical Group PC-Robert Packer Hospital	Sayre	Pennsylvania
United States	Maine Medical Center- Scarborough Campus	Scarborough	Maine
United States	Mayo Clinic in Arizona	Scottsdale	Arizona
United States	Greenville Health System Cancer Institute-Seneca	Seneca	South Carolina
United States	Siouxland Regional Cancer Center	Sioux City	Iowa
United States	Greenville Health System Cancer Institute-Spartanburg	Spartanburg	South Carolina
United States	Spartanburg Medical Center	Spartanburg	South Carolina
United States	CoxHealth South Hospital	Springfield	Missouri
United States	Memorial Medical Center	Springfield	Illinois
United States	Staten Island University Hospital	Staten Island	New York
United States	Cleveland Clinic Cancer Center Strongsville	Strongsville	Ohio
United States	Robert and Carol Weissman Cancer Center at Martin Health	Stuart	Florida
United States	State University of New York Upstate Medical University	Syracuse	New York
United States	Moffitt Cancer Center	Tampa	Florida
United States	Community Medical Center	Toms River	New Jersey
United States	Gene Upshaw Memorial Tahoe Forest Cancer Center	Truckee	California
United States	Natalie Warren Bryant Cancer Center at Saint Francis	Tulsa	Oklahoma
United States	PeaceHealth Southwest Medical Center	Vancouver	Washington
United States	Virtua Voorhees	Voorhees	New Jersey
United States	ProHealth Waukesha Memorial Hospital	Waukesha	Wisconsin
United States	The Alyce and Elmore Kraemer Cancer Care Center	West Bend	Wisconsin
United States	Rice Memorial Hospital	Willmar	Minnesota
United States	Wake Forest University Health Sciences	Winston-Salem	North Carolina
United States	Cleveland Clinic Wooster Family Health and Surgery Center	Wooster	Ohio
United States	Lankenau Medical Center	Wynnewood	Pennsylvania

Sponsors (2)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)	NRG Oncology

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Correlation Between Clinical Outcomes and Tumor Molecular Aberrations		Baseline