High-Dose or Standard-Dose Radiation Therapy and Chemotherapy With or Without Cetuximab in Treating Patients With Newly Diagnosed Stage III Non-Small Cell Lung Cancer That Cannot Be Removed by Surgery

Lung Cancer Clinical Trial

Official title:

A Randomized Phase III Comparison of Standard-Dose (60 Gy) Versus High-Dose (74 Gy) Conformal Radiotherapy With Concurrent and Consolidation Carboplatin/Paclitaxel +/- Cetuximab (IND #103444) in Patients With Stage IIIA/IIIB Non-Small Cell Lung Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00533949
• Other study ID #: RTOG 0617
• Secondary ID: CDR0000564240NCC
• Status: Completed
• Phase: Phase 3
• Start date: November 2007
• Est. completion date: May 20, 2022

Study information

• Verified date: May 2022
• Source: Radiation Therapy Oncology Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

RATIONALE: Radiation therapy uses high-energy x-rays to kill tumor cells. Drugs used in chemotherapy, such as paclitaxel, carboplatin work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as cetuximab can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. It is not yet known whether high-dose radiation therapy is more effective than standard-dose radiation therapy when given together with combination chemotherapy with or without cetuximab in treating patients with non-small cell lung cancer.

PURPOSE: This randomized phase III trial is studying high-dose or standard-dose radiation therapy given together with chemotherapy with or without cetuximab to see how well they work in treating patients with newly diagnosed stage III non-small cell lung cancer that cannot be removed by surgery.

Description:

OBJECTIVES:

Primary

• To compare the overall survival of patients with newly diagnosed, unresectable stage IIIA or IIIB non-small cell lung cancer treated with high- versus standard-dose conformal radiotherapy with concurrent and consolidation chemotherapy comprising carboplatin and paclitaxel.

• To compare the overall survival of patients treated with versus without cetuximab in the setting of concurrent chemotherapy

Secondary

• To compare progression-free survival and local-regional tumor control in patients treated with these regimens.

• To compare the toxicity of high- versus standard-dose conformal radiotherapy and concurrent chemotherapy with versus without cetuximab in these patients.

• To investigate the prognostic and predictive effects of gross tumor volume on overall survival of patients treated with these regimens.

• To compare the quality of life of patients treated with these regimens.

• To correlate outcomes (i.e., survival, toxicity, or QOL) in these patients with biological parameters.

• To analyze the predictive value of pre-treatment standardized uptake value (SUV) of positron emission tomography (PET) scan in predicting survival, distant metastasis, and local-regional control in patients treated with these regimens.

• To explore biological markers to predict clinical outcome including survival, distant metastasis, local-regional control, and QOL (including toxicity) in patients treated with these regimens.

• To prospectively collect and bank tissue, blood, and urine specimens for future biomarker analyses in predicting clinical outcome in patients treated with these regimens.

• To investigate associations between epidermal growth factor receptor (EGFR) expression and toxicity, response, overall survival, and progression-free survival.

OUTLINE: This is a multicenter study. Patients are stratified according to PET staging (yes vs no), radiotherapy technique (3-dimensional conformal radiotherapy vs intensity-modulated radiotherapy), Zubrod performance status (0 vs 1), and histology (squamous vs non-squamous). Patients are randomized to 1 of 4 treatment arms. (Arms II and IV closed to accrual effective 6/17/11)

Patients may undergo tumor tissue, blood, and urine collection periodically during study for tissue banking or biomarker correlative studies.

Patients may undergo quality-of-life assessment at baseline and periodically during study.

After completion of study therapy, patients are followed periodically for 5 years and then annually thereafter.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 544
• Est. completion date: May 20, 2022
• Est. primary completion date: June 2013
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion criteria:

1. Pathologically proven (either histologic or cytologic) diagnosis of Stage IIIA or IIIB non-small cell lung cancer (NSCLC); excluding patients with N3 disease based on supraclavicular or contralateral hilar adenopathy, [according to American Joint Committee on Cancer (AJCC) Staging, 6th edition; see appendix III] within 12 weeks of registration; patients who present with N2 or N3 disease and an undetectable NSCLC primary tumor also are eligible.

2. Patients must be considered unresectable or inoperable; Note: Patients who have had a nodal recurrence after surgery for an early-stage NSCLC are eligible if the following criteria are met:

• Nodal recurrence must be N1 or N2; N3 is not eligible.

• The initial primary must have been staged as T1-2, N0, M0.

• The node must be biopsied within 12 weeks of registration.

• The node must be measurable.

• The patient must not have received prior chemotherapy or radiation for this lung cancer.

• Prior curative surgery must have been at least 6 months prior to the nodal recurrence.

• The exception to a prior invasive malignancy does not apply to the initial lung primary.

3. Stage III A or B disease, including no distant metastases, based upon the following minimum diagnostic workup are acceptable:

• History/physical examination, including documentation of height, weight, body surface area (BSA), and vital signs within 8 weeks prior to registration;

• Computed tomographic (CT)/Magnetic Resonance Imaging (MRI) imaging of the lung and upper abdomen through the adrenal glands within 6 weeks prior to registration;

• An MRI of the brain with contrast (or CT with contrast if MRI is medically contraindicated) within 6 weeks prior to registration; Note: The use of intravenous contrast is required for the MRI or CT. An MRI without contrast is only permitted if the patient has a contrast allergy.

• Whole-body fluorodeoxyglucose (FDG) - Positron Emission Tomography(PET) or PET/CT or if no PET is available, a bone scan is required within 6 weeks prior to registration; Note: If a PET is done that shows clear adrenals and lungs, then a CT scan of chest only is permitted.

4. If a pleural effusion is present, the following criteria must be met to exclude malignant involvement (incurable T4 disease):

• When pleural fluid is visible on both the CT scan and on a chest x-ray, a pleuracentesis is required to confirm that the pleural fluid is cytologically negative.

• Exudative pleural effusions are excluded, regardless of cytology;

• Effusions that are minimal (i.e. not visible on chest x-ray) that are too small to safely tap are eligible.

5. Patients must have measurable or evaluable disease.

6. Patients with post-obstructive pneumonia are eligible.

7. Patients must be at least 3 weeks from prior thoracotomy (if performed).

8. Zubrod Performance Status 0-1;

9. Age = 18;

10. Pulmonary function tests (PFTs) including forced expiratory volume in one second (FEV1) within 12 weeks prior to registration; for FEV1, the best value obtained pre- or post bronchodilator must be = 1.2 liters/second or = 50% predicted.

11. Complete blood count (CBC)/differential obtained within 2 weeks prior to registration on study, with adequate bone marrow function defined as follows:

• Absolute neutrophil count (ANC) = 1,800 cells/mm3;

• Platelets = 100,000 cells/mm3;

• Hemoglobin = 10.0 g/dl (Note: The use of transfusion or other intervention to achieve Hgb = 10.0 g/dl is acceptable.)

12. Serum creatinine within normal institutional limits or creatinine clearance =60 ml/min;

13. Bilirubin must be within or below normal institutional limits;

14. Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) < 2.5 x the institutional upper limit of normal (IULN);

15. Patient must sign study specific informed consent prior to study entry.

Exclusion Criteria:

1. N3 supraclavicular disease;

2. Greater than minimal, exudative, or cytologically positive pleural effusions;

3. Involved contralateral hilar nodes (i.e. greater than 1.5 cm on short axis or positive on PET scan);

4. = 10% weight loss within the past month;

5. Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for a minimum of 3 years; non-invasive conditions such as carcinoma in situ of the breast, oral cavity, or cervix are all permissible.

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

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

8. Prior therapy that specifically and directly targets the epidermal growth factor receptor (EGFR) pathway;

9. Prior severe infusion reaction to a monoclonal antibody;

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

• Significant history of uncontrolled cardiac disease; i.e., uncontrolled hypertension, unstable angina, myocardial infarction within the last 6 months, uncontrolled congestive heart failure, and cardiomyopathy with decreased ejection fraction.

• 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 within 30 days before 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. The need to exclude patients with AIDS from this protocol is necessary because the treatments involved in this protocol may be significantly immunosuppressive. Protocol-specific requirements may also exclude immuno-compromised patients.

11. Pregnancy or women of childbearing potential and men who are sexually active and not willing/able to use medically acceptable forms of contraception; this exclusion is necessary because the treatment involved in this study may be significantly teratogenic.

12. Any history of allergic reaction to paclitaxel or other taxanes, or to carboplatin;

13. Uncontrolled neuropathy grade 2 or greater regardless of cause.

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Cancer
• Lung Neoplasms
• Radiation Toxicity

Intervention

Biological:
• Cetuximab
Loading dose: 400 mg/m2, IV, one week prior to start of radiation therapy (RT). Then, beginning day 1 of RT, 250 mg/m2, IV, weekly; for 60 Gy arm for 15 weeks, for 74 Gy arm for 16 weeks.

Drug:
• Carboplatin
Concurrent: AUC=2, IV, days 1, 8, 14, 22, 29, and 36 of radiation therapy; for 74 Gy arms, on day 43 as well. Consolidation, 3 weeks after completion of RT, AUC=6, IV, days 1 and 22.
• Paclitaxel
Concurrent: 45 mg/m2, IV, days 1, 8, 14, 22, 29, and 36 of radiation therapy (RT); for 74 Gy arms, on day 43 as well. Consolidation, 3 weeks after completion of RT, 200 mg/m2, IV, days 1 and 22.

Radiation:
• 60 Gy RT
Radiation therapy (RT) in once-daily, 2 Gy fractions, given in 30 fractions over the course of 6 weeks.
• 74 Gy RT
Radiation therapy (RT) in once-daily, 2 Gy fractions, given in 37 fractions over the course of 7.5 weeks.

Locations

Country	Name	City	State
Canada	Tom Baker Cancer Centre - Calgary	Calgary	Alberta
Canada	Hopital Notre-Dame du CHUM	Montreal	Quebec
Canada	Allan Blair Cancer Centre at Pasqua Hospital	Regina	Saskatchewan
Canada	Saskatoon Cancer Centre at the University of Saskatchewan	Saskatoon	Saskatchewan
Canada	Princess Margaret Hospital	Toronto	Ontario
Canada	CancerCare Manitoba	Winnipeg	Manitoba
United States	McDowell Cancer Center at Akron General Medical Center	Akron	Ohio
United States	Summa Center for Cancer Care at Akron City Hospital	Akron	Ohio
United States	New York Oncology Hematology, PC at Albany Regional Cancer Care	Albany	New York
United States	Veterans Affairs Medical Center - Albany	Albany	New York
United States	University of New Mexico Cancer Center	Albuquerque	New Mexico
United States	Tulane Cancer Center Office of Clinical Research	Alexandria	Louisiana
United States	Morgan Cancer Center at Lehigh Valley Hospital - Cedar Crest	Allentown	Pennsylvania
United States	Harrington Cancer Center	Amarillo	Texas
United States	Saint Joseph Mercy Cancer Center	Ann Arbor	Michigan
United States	Theda Care Cancer Institute	Appleton	Wisconsin
United States	Texas Oncology, PA at Texas Cancer Center - Arlington South	Arlington	Texas
United States	Emory Crawford Long Hospital	Atlanta	Georgia
United States	Georgia Cancer Center for Excellence at Grady Memorial Hospital	Atlanta	Georgia
United States	Piedmont Hospital	Atlanta	Georgia
United States	Winship Cancer Institute of Emory University	Atlanta	Georgia
United States	Greenebaum Cancer Center at University of Maryland Medical Center	Baltimore	Maryland
United States	St. Agnes Hospital Cancer Center	Baltimore	Maryland
United States	Barberton Citizens Hospital	Barberton	Ohio
United States	Mary Bird Perkins Cancer Center - Baton Rouge	Baton Rouge	Louisiana
United States	Texas Oncology, PA at Harris Center HEB	Bedford	Texas
United States	Billings Clinic - Downtown	Billings	Montana
United States	UAB Comprehensive Cancer Center	Birmingham	Alabama
United States	Mountain States Tumor Institute at St. Luke's Regional Medical Center	Boise	Idaho
United States	Saint Alphonsus Cancer Care Center at Saint Alphonsus Regional Medical Center	Boise	Idaho
United States	Bryn Mawr Hospital	Bryn Mawr	Pennsylvania
United States	Alamance Cancer Center at Alamance Regional Medical Center	Burlington	North Carolina
United States	Fletcher Allen Health Care - University Health Center Campus	Burlington	Vermont
United States	Fairview Ridges Hospital	Burnsville	Minnesota
United States	Sands Cancer Center	Canandaigua	New York
United States	Aultman Cancer Center at Aultman Hospital	Canton	Ohio
United States	Mercy Cancer Center at Mercy San Juan Medical Center	Carmichael	California
United States	Mercy Regional Cancer Center at Mercy Medical Center	Cedar Rapids	Iowa
United States	Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill	Chapel Hill	North Carolina
United States	Hollings Cancer Center at Medical University of South Carolina	Charleston	South Carolina
United States	Blumenthal Cancer Center at Carolinas Medical Center	Charlotte	North Carolina
United States	Presbyterian Cancer Center at Presbyterian Hospital	Charlotte	North Carolina
United States	University of Virginia Cancer Center	Charlottesville	Virginia
United States	Creticos Cancer Center at Advocate Illinois Masonic Medical Center	Chicago	Illinois
United States	University of Chicago Cancer Research Center	Chicago	Illinois
United States	Enloe Cancer Center at Enloe Medical Center	Chico	California
United States	Adena Regional Medical Center	Chillicothe	Ohio
United States	Charles M. Barrett Cancer Center at University Hospital	Cincinnati	Ohio
United States	Case Comprehensive Cancer Center	Cleveland	Ohio
United States	Cleveland Clinic Cancer Center at Fairview Hospital	Cleveland	Ohio
United States	Cleveland Clinic Taussig Cancer Center	Cleveland	Ohio
United States	Penrose Cancer Center at Penrose Hospital	Colorado Springs	Colorado
United States	Riverside Methodist Hospital Cancer Care	Columbus	Ohio
United States	Cancer Care Center at John Muir Health - Concord Campus	Concord	California
United States	Payson Center for Cancer Care at Concord Hospital	Concord	New Hampshire
United States	Geisinger Cancer Institute at Geisinger Health	Danville	Pennsylvania
United States	Charles B. Eberhart Cancer Center at DeKalb Medical Center	Decatur	Georgia
United States	Texas Oncology, PA at Texas Cancer Center - Denton South	Denton	Texas
United States	John Stoddard Cancer Center at Iowa Methodist Medical Center	Des Moines	Iowa
United States	Mercy Cancer Center at Mercy Medical Center - Des Moines	Des Moines	Iowa
United States	Barbara Ann Karmanos Cancer Institute	Detroit	Michigan
United States	Josephine Ford Cancer Center at Henry Ford Hospital	Detroit	Michigan
United States	Northeast Radiation Oncology Center	Dunmore	Pennsylvania
United States	Dale and Frances Hughes Cancer Center at Pocono Medical Center	East Stroudsburg	Pennsylvania
United States	Shore Regional Cancer Center at Memorial Hospital - Easton	Easton	Maryland
United States	Luther Midlelfort Hospital	Eau Claire	Wisconsin
United States	Midelfort Clinic - Luther	Eau Claire	Wisconsin
United States	Swedish Medical Center	Englewood	Colorado
United States	Regional Cancer Center - Erie	Erie	Pennsylvania
United States	Willamette Valley Cancer Center - Eugene	Eugene	Oregon
United States	Center for Cancer Care at Exeter Hospital	Exeter	New Hampshire
United States	CCOP - MeritCare Hospital	Fargo	North Dakota
United States	Poudre Valley Radiation Oncology	Fort Collins	Colorado
United States	Broward General Medical Center Cancer Center	Fort Lauderdale	Florida
United States	Parkview Regional Cancer Center at Parkview Health	Fort Wayne	Indiana
United States	Radiation Oncology Associates Southwest	Fort Wayne	Indiana
United States	Klabzuba Cancer Center at Harris Methodist Fort Worth Hospital	Fort Worth	Texas
United States	Saint Agnes Cancer Center at Saint Agnes Medical Center	Fresno	California
United States	University of Florida Shands Cancer Center	Gainesville	Florida
United States	Center for Cancer Care at Goshen General Hospital	Goshen	Indiana
United States	Altru Cancer Center at Altru Hospital	Grand Forks	North Dakota
United States	Lacks Cancer Center at Saint Mary's Health Care	Grand Rapids	Michigan
United States	Bellin Memorial Hospital	Green Bay	Wisconsin
United States	St. Mary's Hospital Medical Center - Green Bay	Green Bay	Wisconsin
United States	St. Vincent Hospital Regional Cancer Center	Green Bay	Wisconsin
United States	Cancer Centers of the Carolinas - Faris Road	Greenville	South Carolina
United States	CCOP - Greenville	Greenville	South Carolina
United States	Van Elslander Cancer Center at St. John Hospital and Medical Center	Grosse Pointe Woods	Michigan
United States	Penn State Hershey Cancer Institute at Milton S. Hershey Medical Center	Hershey	Pennsylvania
United States	Memorial Cancer Institute at Memorial Regional Hospital	Hollywood	Florida
United States	M. D. Anderson Cancer Center at University of Texas	Houston	Texas
United States	Cleveland Clinic Cancer Center	Independence	Ohio
United States	Central Indiana Cancer Centers - East	Indianapolis	Indiana
United States	Community Regional Cancer Care at Community Hospital East	Indianapolis	Indiana
United States	Community Regional Cancer Care at Community Hospital North	Indianapolis	Indiana
United States	University of Mississippi Cancer Clinic	Jackson	Mississippi
United States	Baptist Cancer Institute - Jacksonville	Jacksonville	Florida
United States	Baptist Medical Center South	Jacksonville	Florida
United States	Integrated Community Oncology Network at Southside Cancer Center	Jacksonville	Florida
United States	Mayo Clinic - Jacksonville	Jacksonville	Florida
United States	Integrated Community Oncology Network	Jacksonville Beach	Florida
United States	Ella Milbank Foshay Cancer Center at Jupiter Medical Center	Jupiter	Florida
United States	West Michigan Cancer Center	Kalamazoo	Michigan
United States	Good Samaritan Cancer Center at Good Samaritan Hospital	Kearney	Nebraska
United States	Christine LaGuardia Phillips Cancer Center at Wellmont Holston Valley Medical Center	Kingsport	Tennessee
United States	Kinston Medical Specialists	Kinston	North Carolina
United States	Gundersen Lutheran Center for Cancer and Blood	La Crosse	Wisconsin
United States	Rebecca and John Moores UCSD Cancer Center	La Jolla	California
United States	CCOP - Nevada Cancer Research Foundation	Las Vegas	Nevada
United States	Central Baptist Hospital	Lexington	Kentucky
United States	Saint Elizabeth Cancer Institute at Saint Elizabeth Regional Medical Center	Lincoln	Nebraska
United States	St. Mary Mercy Hospital	Livonia	Michigan
United States	Longview Cancer Center	Longview	Texas
United States	Elliot Regional Cancer Center at Elliot Hospital	Manchester	New Hampshire
United States	Minnesota Oncology Hematology, PA - Maplewood	Maplewood	Minnesota
United States	Bay Area Cancer Care Center at Bay Area Medical Center	Marinette	Wisconsin
United States	Fox Chase Virtua Health Cancer Program at Virtua Memorial Hospital Marlton	Marlton	New Jersey
United States	Mercy Cancer Center at Mercy Medical Center - North Iowa	Mason City	Iowa
United States	Hillcrest Cancer Center at Hillcrest Hospital	Mayfield Heights	Ohio
United States	Baptist-South Miami Regional Cancer Program	Miami	Florida
United States	CCOP - Mount Sinai Medical Center	Miami Beach	Florida
United States	Southwest General Health Center	Middleburg Heights	Ohio
United States	Medical College of Wisconsin Cancer Center	Milwaukee	Wisconsin
United States	Veterans Affairs Medical Center - Milwaukee	Milwaukee	Wisconsin
United States	Virginia Piper Cancer Institute at Abbott - Northwestern Hospital	Minneapolis	Minnesota
United States	Trinity CancerCare Center	Minot	North Dakota
United States	Memorial Medical Center	Modesto	California
United States	D.N. Greenwald Center	Mukwonago	Wisconsin
United States	Cancer Center at Ball Memorial Hospital	Muncie	Indiana
United States	Jon and Karen Huntsman Cancer Center at Intermountain Medical Center	Murray	Utah
United States	CCOP - Ochsner	New Orleans	Louisiana
United States	MBCCOP - LSU Health Sciences Center	New Orleans	Louisiana
United States	St. Luke's - Roosevelt Hospital Center - St.Luke's Division	New York	New York
United States	CCOP - Christiana Care Health Services	Newark	Delaware
United States	UMDNJ University Hospital	Newark	New Jersey
United States	Community Cancer Center	Normal	Illinois
United States	West Texas Cancer Center	Odessa	Texas
United States	Oklahoma University Cancer Institute	Oklahoma City	Oklahoma
United States	Methodist Estabrook Cancer Center	Omaha	Nebraska
United States	St. Joseph Hospital Regional Cancer Center - Orange	Orange	California
United States	Integrated Community Oncology Network - Orange Park	Orange Park	Florida
United States	UHHS Chagrin Highlands Medical Center	Orange Village	Ohio
United States	St. Charles Mercy Hospital	Oregon	Ohio
United States	M.D. Anderson Cancer Center at Orlando	Orlando	Florida
United States	Florida Cancer Center - Palatka	Palatka	Florida
United States	Cancer Center of Paoli Memorial Hospital	Paoli	Pennsylvania
United States	Feather River Hospital Cancer Center	Paradise	California
United States	Regional Cancer Center at Singing River Hospital	Pascagoula	Mississippi
United States	Cancer Treatment Center at Pekin Hospital	Pekin	Illinois
United States	Sacred Heart Cancer Center at Sacred Heart Hospital	Pensacola	Florida
United States	Methodist Medical Center of Illinois	Peoria	Illinois
United States	OSF St. Francis Medical Center	Peoria	Illinois
United States	Albert Einstein Cancer Center	Philadelphia	Pennsylvania
United States	Fox Chase Cancer Center - Philadelphia	Philadelphia	Pennsylvania
United States	Frankford Hospital Cancer Center - Torresdale Campus	Philadelphia	Pennsylvania
United States	Kimmel Cancer Center at Thomas Jefferson University - Philadelphia	Philadelphia	Pennsylvania
United States	FirstHealth Moore Regional Community Hospital Comprehensive Cancer Center	Pinehurst	North Carolina
United States	Mercy Regional Cancer Center at Mercy Hospital	Port Huron	Michigan
United States	Utah Valley Regional Medical Center - Provo	Provo	Utah
United States	All Saints Cancer Center at Wheaton Franciscan Healthcare	Racine	Wisconsin
United States	Cancer Centers of North Carolina - Raleigh	Raleigh	North Carolina
United States	McGlinn Family Regional Cancer Center at Reading Hospital and Medical Center	Reading	Pennsylvania
United States	Renown Institute for Cancer at Renown Regional Medical Center	Reno	Nevada
United States	Saint Mary's Regional Medical Center	Reno	Nevada
United States	Humphrey Cancer Center at North Memorial Outpatient Center	Robbinsdale	Minnesota
United States	Highland Hospital of Rochester	Rochester	New York
United States	James P. Wilmot Cancer Center at University of Rochester Medical Center	Rochester	New York
United States	Mayo Clinic Cancer Center	Rochester	Minnesota
United States	University Radiation Oncology at Parkridge Hospital	Rochester	New York
United States	Radiation Oncology Center - Roseville	Roseville	California
United States	Radiological Associates of Sacramento Medical Group, Incorporated	Sacramento	California
United States	University of California Davis Cancer Center	Sacramento	California
United States	Flagler Cancer Center	Saint Augustine	Florida
United States	CentraCare Clinic - River Campus	Saint Cloud	Minnesota
United States	Dixie Regional Medical Center - East Campus	Saint George	Utah
United States	Saint Helena Hospital	Saint Helena	California
United States	Barnes-Jewish West County Hospital	Saint Louis	Missouri
United States	Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis	Saint Louis	Missouri
United States	Regions Hospital Cancer Care Center	Saint Paul	Minnesota
United States	Siteman Cancer Center at Barnes-Jewish St. Peters Hospital - St. Peters	Saint Peters	Missouri
United States	Peninsula Regional Medical Center	Salisbury	Maryland
United States	Utah Cancer Specialists at UCS Cancer Center	Salt Lake City	Utah
United States	Cancer Care Centers of South Texas - Northeast	San Antonio	Texas
United States	UCSF Helen Diller Family Comprehensive Cancer Center	San Francisco	California
United States	North Coast Cancer Care, Incorporated	Sandusky	Ohio
United States	Mayo Clinic Scottsdale	Scottsdale	Arizona
United States	CCOP - Virginia Mason Research Center	Seattle	Washington
United States	Cancer Centers of the Carolinas - Seneca	Seneca	South Carolina
United States	Texas Oncology, PA at Texas Cancer Center - Sherman	Sherman	Texas
United States	Siouxland Hematology-Oncology Associates, LLP	Sioux City	Iowa
United States	Sanford Cancer Center at Sanford USD Medical Center	Sioux Falls	South Dakota
United States	Gibbs Regional Cancer Center at Spartanburg Regional Medical Center	Spartanburg	South Carolina
United States	Cancer Care Northwest - Spokane South	Spokane	Washington
United States	Baystate Regional Cancer Program at D'Amour Center for Cancer Care	Springfield	Massachusetts
United States	Stanford Cancer Center	Stanford	California
United States	Door County Cancer Center at Door County Memorial Hospital	Sturgeon Bay	Wisconsin
United States	Texas Oncology, PA at Texas Oncology Cancer Center Sugar Land	Sugar Land	Texas
United States	Flower Hospital Cancer Center	Sylvania	Ohio
United States	SUNY Upstate Medical University Hospital	Syracuse	New York
United States	North Suburban Medical Center	Thornton	Colorado
United States	St. Anne Mercy Hospital	Toledo	Ohio
United States	J. Phillip Citta Regional Cancer Center at Community Medical Center	Toms River	New Jersey
United States	Arizona Oncology - Tucson	Tucson	Arizona
United States	Natalie Warren Bryant Cancer Center at St. Francis Hospital	Tulsa	Oklahoma
United States	Tyler Cancer Center	Tyler	Texas
United States	Cancer Institute of New Jersey at Cooper - Voorhees	Voorhees	New Jersey
United States	Washington Cancer Institute at Washington Hospital Center	Washington	District of Columbia
United States	Waukesha Memorial Hospital Regional Cancer Center	Waukesha	Wisconsin
United States	UHHS Westlake Medical Center	Westlake	Ohio
United States	Frank M. and Dorothea Henry Cancer Center at Geisinger Wyoming Valley Medical Center	Wilkes-Barre	Pennsylvania
United States	Riverview UW Cancer Center at Riverview Hospital	Wisconsin Rapids	Wisconsin
United States	Cleveland Clinic - Wooster	Wooster	Ohio
United States	Lankenau Cancer Center at Lankenau Hospital	Wynnewood	Pennsylvania

Sponsors (5)

Lead Sponsor	Collaborator
Radiation Therapy Oncology Group	Cancer and Leukemia Group B, National Cancer Institute (NCI), North Central Cancer Treatment Group, NRG Oncology

Countries where clinical trial is conducted

United States,  Canada, 

References & Publications (1)

Bradley JD, Hu C, Komaki RR, Masters GA, Blumenschein GR, Schild SE, Bogart JA, Forster KM, Magliocco AM, Kavadi VS, Narayan S, Iyengar P, Robinson CG, Wynn RB, Koprowski CD, Olson MR, Meng J, Paulus R, Curran WJ Jr, Choy H. Long-Term Results of NRG Oncol — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Survival	Survival time is defined as time from randomization to date of death from any cause and is estimated by the Kaplan-Meier method. Patients last known to be alive are censored at the date of last contact.	From randomization to last follow-up. Analysis occured after all patients were on study for 18 months. Maximum follow-up at time of analysis was 61.5 months.
Secondary	Progression-free Survival	A failure for progression-free survival (PFS) is the first occurrence of local or regional progression, distant metastases, or death from any cause. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a nontarget lesion, or the appearance of new lesions. Time is measured from the date of randomization to the date of first failure. Patients without failure are censored at the date of last follow-up.	From randomization to last follow-up. Analysis occured after all patients were on study for 18 months. Maximum follow-up at time of analysis was 61.5 months.
Secondary	Local-regional Failure (Reported as Two-year Estimates)	A failure for local-regional failure is the first occurrence of local or regional progression. Time is measured from the date of randomization to the date of first failure. Patients alive without local or regional failure at the time of last follow-up are censored. Patients who died without local or regional failure are considered as having competing risk at the time of death. Local-regional failure was estimated by the cumulative incidence method and 2 year estimates are reported.	From randomization to last follow-up. Analysis occured after all patients were on study for 18 months. Maximum follow-up at time of analysis was 61.5 months.
Secondary	Percentage of Participants With Grade 3-5 Esophagitis and Pneumonitis Adverse Events as Assessed by NCI Common Toxicity Criteria for Adverse Effects (CTCAE) v3.0	Treatment-related esophagitis and pneumonitis were assessed graded using the CTCAE v3.0. Comparisons are only made between radiation therapy dosing levels because the cetuximab regimen was known to be safe in combination with radiation therapy.	From randomization to last follow-up. Analysis occured after all patients were on study for 18 months. Maximum follow-up at time of analysis was 61.5 months.
Secondary	Percentage of Participants With Other Grade 3-5 Adverse Events as Assessed by NCI CTCAE v3.0	Treatment-related adverse events other than esophagitis and pneumonitis were assessed graded using the CTCAE v3.0. Comparisons are only made between radiation therapy dosing levels because the cetuximab regimen was known to be safe in combination with radiation therapy.	From randomization to last follow-up. Analysis occured after all patients were on study for 18 months. Maximum follow-up at time of analysis was 61.5 months.
Secondary	Death During or Within 30 Days of Discontinuation of Protocol Treatment	Deaths regardless of cause and occuring during or within 30 days of discontinuation of protocol treatment were evaluated.	From start of protocol treatment to 24 months.
Secondary	Percentage of Patients With Decline From Baseline to 3 Months in the Lung Cancer Subscale (LCS) of the Functional Assessment of the Cancer Therapy Trial Outcome Index (FACT-TOI).	A decline of 2 points in the LCS from baseline to 3 months was considered a clinically meaningful change indicating a decline in quality of life. Comparisons are only made between radiation therapy dosing levels because the cetuximab regimen was known to be safe in combination with radiation therapy.	At baseline and 3 months.
Secondary	Patient-reported Swallowing Score (Area Under the Curve)	Patients completed a swallowing diary prior to the start of treatment and then daily during treatment. Patients recorded a score to indicate problems with swallowing on that day (1-None, 2-Mild soreness only, 3-Can swallow solids with some difficulty, 4-Cannot swallow solids, 5-Cannot swallow liquids). These scores were then plotted across time and the area under the curve from baseline until the end of week 6 was calculated. A lower area under the curve indicates better swallowing ability. Comparisons are only made between radiation therapy dosing levels because the cetuximab regimen was known to be safe in combination with radiation therapy.	From randomization to 6 weeks after start of radiation therapy (6-10 weeks from randomization)
Secondary	EuroQoL (EQ5D) Visual Analog Scale (VAS) Through One Year (Area Under the Curve)	The visual analogue scale is a self-assessment of current health state, measured on a 20-cm scale ranging from 0 for the worst imaginable health state to 100 for best imaginable health state, marked at 10-point intervals. The area under the curve of each subject's EQ5D visual analog scale (VAS) response trajectory within 1 year was calculated. The EQ5D VAS utility was normalized by the baseline score. The trajectory included all available time points through one year. If a subject died within one year, the EQ5D VAS was reduced to 0 at the time of death. If subject was censored within one year, the EQ5D utility curve was truncated at the time of censoring. The scores were plotted across time and the area under the curve was calculated. A greater area under the curve indicates a better health state. Comparisons are only made between radiation therapy dosing levels because the cetuximab regimen was known to be safe in combination with radiation	From randomization to one year
Secondary	Overall Survival and Local-regional Failure by Epithelial Growth Factor Receptor (EGFR) Group	EGFR is a protein that is present on the surface of both normal cells and cancer cancer cells. EGFR H-Score is a measure of staining intensity ranging from 0 to 300 where a higher value indicates greater intensity of EGFR. Available tumor samples were evaluated for EGFR and given an H-Score. Patients were divided into two groups based on H-Score values dichotomized at 200. All event times are time from randomization to date of event or censoring. A survival event is death from any cause, patients without events are censored at the date of last contact, and survival rates are estimated by Kaplan-Meier method. A local-regional event is the first development of progressive disease locally or regionally, patients who do not have an event are censored at the date of death or last contact, and event rates are estimated by cumulative incidence. Two-year rates are reported.	From randomization to last follow-up. Analysis occured after all patients were on study for 18 months. Maximum follow-up at time of analysis was 61.5 months.
Secondary	Percentage of Patients With Grade 3+ Adverse Events by Epithelial Growth Factor Receptor (EGFR) Group	EGFR is a protein that is present on the surface of both normal cells and cancer cancer cells. EGFR H-Score is a measure of staining intensity ranging from 0 to 300 where a higher value indicates greater intensity of EGFR. Available tumor samples were evaluated for EGFR and given an H-Score. Patients were divided into two groups based on H-Score values dichotomized at 200. Worst toxicity as determined by adverse events was used as a measure of a patient's quality of life (QOL). Adverse events were graded using the Common Terminology Criteria for Adverse Events (CTCAE) v3.0. Grade refers to the severity of the AE. The CTCAE v3.0 assigns Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1 Mild, Grade 2 Moderate, Grade 3 Severe, Grade 4 Life-threatening or disabling, Grade 5 Death related to AE. Highest grade (worst) adverse event (AE) per subject was counted.	From randomization to last follow-up. Analysis occured after all patients were on study for 18 months. Maximum follow-up at time of analysis was 61.5 months.
Secondary	Prognostic and Predictive Effects of Gross Tumor Volume (GTV) on Overall Survival	Gross tumor volume (GTV) is defined as the combined volume (cubic centimeters) of the primary tumor and clinically positive lymph nodes seen either on the planning computed tomography (CT) scan or the pretreatment positron emission tomography (PET) scan. Survival time is defined as time from randomization to date of death from any cause and is estimated by the Kaplan-Meier method. Patients last known to be alive are censored at the date of last contact. GTV was evaluated as a continuous variable therefore overall survival time is not summarized by GTV. "Prognostic" refers to the main effect and "predictive" refers to the interaction between GTV and treatment arm.	From randomization to last follow-up. Analysis occured after all patients were on study for 18 months. Maximum follow-up at time of analysis was 61.5 months.
Secondary	Prognostic Value of Pre-treatment Standardized Uptake Value (SUV) of Positron Emission Tomography (PET) Scan in Predicting Survival, Distant Metastasis, and Local-regional Failure	Standardized uptake value (SUV) is a simple way of determining activity in PET imaging. It is a mathematically derived ratio of tissue radioactivity concentration at a point in time and the injected dose of radioactivity per kilogram of the patient's body weight. All event times are time from randomization to date of event or censoring. A survival event is death from any cause, patients without events are censored at the date of last contact, and survival rates are estimated by Kaplan-Meier method. Local-regional and distant metastasis events are the first development of progressive disease locally/regionally or distant metastasis, respectively, patients who do not have an event are censored at the date of death or last contact, and event rates are estimated by cumulative incidence. Two-year rates are presented. PET SUV was evaluated as a continuous variable therefore the outcome variables are not summarized by PET SUV.	From randomization to last follow-up. Analysis occured after all patients were on study for 18 months. Maximum follow-up at time of analysis was 61.5 months.

External Links

•   Data Available: Select individual patient-level data from this trial can be requested from the NCTN/NCORP Data Archive.