Radiation Therapy and Cisplatin With or Without Cetuximab in Treating Patients With Stage III or Stage IV Head and Neck Cancer

Head and Neck Cancer Clinical Trial

Official title:

A Randomized Phase III Trial of Concurrent Accelerated Radiation and Cisplatin Versus Concurrent Accelerated Radiation, Cisplatin, and Cetuximab (C225) [Followed by Surgery for Selected Patients] for Stage III and IV Head and Neck Carcinomas

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00265941
• Other study ID #: RTOG 0522
• Secondary ID: CDR0000458049NCI
• Status: Completed
• Phase: Phase 3
• Start date: November 2005
• 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 cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Cisplatin may also make tumor cells more sensitive to radiation therapy. 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. Giving radiation therapy and cisplatin together with cetuximab may kill more tumor cells. It is not yet known whether radiation therapy and cisplatin are more effective with or without cetuximab in treating head and neck cancer. PURPOSE: This randomized phase III trial is studying radiation therapy, cisplatin, and cetuximab to see how well they work compared to radiation therapy and cisplatin in treating patients with stage III or stage IV head and neck cancer.

Description:

OBJECTIVES: Primary - Evaluate whether the addition of cetuximab to a concurrent radiation-cisplatin regimen will improve progression-free survival in patients with stage III or IV squamous cell carcinoma of the oropharynx, hypopharynx, or larynx. Secondary - Determine the impact of the addition of cetuximab to a concurrent radiation-cisplatin regimen on overall survival, local-regional control, acute and late toxic effects, quality of life, and health utilities in these patients. - Correlate the expression of epidermal growth factor receptor (EGFR) and its down-stream molecules with outcome in patients participating in this component of the trial. - Correlate pre-treatment positron emission tomography (PET) scan findings with progression-free survival, overall survival, and local-regional control in patients participating in this component of the trial. - Correlate post-treatment PET scan findings with nodal response and nodal relapse in patients participating in this component of the trial. OUTLINE: This is a randomized, controlled, multicenter study. Patients are stratified according to primary site (larynx vs non-larynx), nodal stage (N0 vs N1, N2a, N2b vs N2c, N3), Zubrod performance status (0 vs 1), use of intensity modulated radiotherapy (IMRT) (no vs yes), and pre-treatment PET/CT scan (no vs yes). Patients are randomized to 1 of 2 treatment arms. NOTE: *A neck dissection is optional for patients with multiple lymph nodes or lymph nodes > 3 cm in diameter who achieve a complete clinical and radiographic response in the neck. Quality of life is assessed at baseline, once during the last 2 weeks of treatment, at 3 and 12 months from the start of treatment, and then annually for 4 years. After completion of study treatment, patients are followed periodically for 5 years and then annually thereafter.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 940
• Est. completion date: May 20, 2022
• Est. primary completion date: January 2011
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion criteria:

• Pathologically (histologically or cytologically) proven (from primary lesion and/or lymph nodes) diagnosis of squamous cell carcinoma of the oropharynx, hypopharynx, or larynx;
• Selected stage III or IV disease (T2N2-3M0, T3-4 any N M0); Note: Patients with T1, any N, or T2N1 tumors are not eligible.
• Appropriate stage for protocol entry, including no distant metastases, based upon the

following minimum diagnostic workup:

• History/physical examination within 4 weeks prior to registration, including assessment of weight and weight loss in past 6 months and an examination by a Medical Oncologist;
• Chest x-ray (or Chest CT scan or PET/CT scan) within 6 weeks prior to registration;
• CT scan or MRI of the head and neck (of the primary tumor and neck nodes) or PET/CT scan within 6 weeks prior to registration; see Section 6.11 for details of PET scans. Note: A PET/CT can only be used instead of a CT scan or MRI if the CT is a high quality scan with contrast.
• Left ejection fraction determined by echocardiogram and/or multiple gated acquisition (MUGA) technique within 12 weeks of registration;
• Zubrod Performance Status 0-1;
• Age > 18;
• Adequate bone marrow function, defined as follows:
• Absolute neutrophil count (ANC) > 1,800 cells/mm3 based upon CBC/differential obtained within 2 weeks prior to registration on study;
• Platelets > 100,000 cells/mm3 based upon complete blood count (CBC)/differential obtained within 2 weeks prior to registration on study;
• Hemoglobin > 8.0 g/dl based upon CBC/differential obtained within 2 weeks prior to registration on study (Note: The use of transfusion or other intervention to achieve Hgb > 8.0 g/dl is acceptable.)
• Adequate hepatic function, defined as follows:
• Bilirubin < 1.5 mg/dl within 2 weeks prior to registration on study; For patients with Gilbert's disease as the sole cause of elevated bilirubin, please contact the PI, Dr. Ang.
• Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) < 2x the upper limit of normal within 2 weeks prior to registration on study;
• Adequate renal function, defined as follows:
• Serum creatinine < 1.5 mg/dl within 2 weeks prior to registration
• Creatinine clearance (CCr) = 50 ml/min within 2 weeks prior to registration determined by 24-hour collection or estimated by Cockcroft-Gault formula: CCr male = [(140 - age) x (wt in kg)]/[(Serum Cr mg/dl) x (72)] CCr female = 0.85 x (CrCl male)
• Pregnancy test within 2 weeks prior to registration for women of childbearing potential;
• Women of childbearing potential and male participants must agree to use a medically effective means of birth control throughout their participation in the treatment phase of the study (until at least 60 days following the last study treatment);
• Patient must sign study specific informed consent prior to study entry.

Exclusion criteria:

• Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for a minimum of 3 years;
• Patients with simultaneous primaries or bilateral tumors are excluded.
• Gross total excision (e.g., by tonsillectomy) of the primary tumor; however, partial removal of the tumor to alleviate an impending airway obstruction does not make the patient ineligible.
• 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;
• Primary site of tumor of oral cavity, nasopharynx, sinuses, or salivary glands;
• Initial surgical treatment, excluding diagnostic biopsy of the primary site or nodal sampling of neck disease; radical or modified neck dissection is not permitted.
• Severe, active co-morbidity, defined as follows:
• Current uncontrolled cardiac disease; i.e., uncontrolled hypertension, unstable angina, recent myocardial infarction (within prior 6 months), uncontrolled congestive heart failure, and cardiomyopathy with decreased ejection fraction;
• Left Ventricular Ejection Fraction < 45%;
• 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;
• Acquired Immune Deficiency Syndrome (AIDS) based upon current Centers for Disease Control and Prevention (CDC) definition; note, however, that 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.
• Any uncontrolled condition, which in the opinion of the investigator, would interfere in the safe and timely completion of study procedures;
• CTCAE, v. 3.0 grade 3-4 electrolyte abnormalities:
• Calcium < 7 mg/dl or > 12.5 mg/dl;
• Glucose < 40 mg/dl or > 250 mg/dl;
• Magnesium < 0.9 mg/dl or > 3 mg/dl;
• Potassium < 3 mmol/L or > 6 mmol/L;
• Sodium < 130 mmol/L or > 155 mmol/L
• Pregnant or lactating women 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.
• Prior allergic reaction to the study drug(s) involved in this protocol;
• Prior therapy that specifically and directly targets the EGFR pathway;
• Prior severe infusion reaction to a monoclonal antibody.

Related Conditions & MeSH terms

• Head and Neck Cancer
• Head and Neck Neoplasms

Intervention

Drug:
• cetuximab
Cetuximab 400 mg/m^2 IV loading dose 5-7 days before start of radiation therapy, then 250 mg/m^2 IV weekly for 7 weeks
• cisplatin
Cisplatin 100 mg/m^2 IV on days 1 and 22

Radiation:
• Accelerated Fractionation by Concomitant Boost
3DCRT 54 Gy in 30 1.8 Gy fractions over 6 weeks with boost 18 Gy in 12 1.5 Gy fractions for last 12 days, for a total of 72 Gy in 42 fractions over 6 weeks
• Intensity-modulated radiation therapy
70 Gy in 35 2.0 Gy fractions over 6 weeks with 6 fractions per week (on Saturday or as second daily fraction) in 5 of the 6 weeks.

Locations

Country	Name	City	State
Canada	Tom Baker Cancer Centre - Calgary	Calgary	Alberta
Canada	Nova Scotia Cancer Centre	Halifax	Nova Scotia
Canada	Hopital Notre-Dame du CHUM	Montreal	Quebec
Canada	McGill Cancer Centre at McGill University	Montreal	Quebec
Canada	Ottawa Hospital Regional Cancer Centre - General Campus	Ottawa	Ontario
Canada	Allan Blair Cancer Centre at Pasqua Hospital	Regina	Saskatchewan
Canada	Northeastern Ontario Regional Cancer Centre	Sudbury	Ontario
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 Mexico Cancer Center	Albuquerque	New Mexico
United States	INOVA Alexandria Hospital	Alexandria	Virginia
United States	Tulane Cancer Center Office of Clinical Research	Alexandria	Louisiana
United States	Saint Anthony's Hospital at Saint Anthony's Health Center	Alton	Illinois
United States	Harrington Cancer Center	Amarillo	Texas
United States	McFarland Clinic, PC	Ames	Iowa
United States	Providence Cancer Center	Anchorage	Alaska
United States	Saint John's Cancer Center at Saint John's Medical Center	Anderson	Indiana
United States	CCOP - Michigan Cancer Research Consortium	Ann Arbor	Michigan
United States	Saint Joseph Mercy Cancer Center	Ann Arbor	Michigan
United States	Theda Care Cancer Institute	Appleton	Wisconsin
United States	Mission Hospitals - Memorial Campus	Asheville	North Carolina
United States	CCOP - Atlanta Regional	Atlanta	Georgia
United States	Emory Crawford Long Hospital	Atlanta	Georgia
United States	Georgia Cancer Center for Excellence at Grady Memorial Hospital	Atlanta	Georgia
United States	Northside Hospital Cancer Center	Atlanta	Georgia
United States	Piedmont Hospital	Atlanta	Georgia
United States	Saint Joseph's Hospital of Atlanta	Atlanta	Georgia
United States	Winship Cancer Institute of Emory University	Atlanta	Georgia
United States	Auburn Radiation Oncology	Auburn	California
United States	Aurora Presbyterian Hospital	Aurora	Colorado
United States	Rush-Copley Cancer Care Center	Aurora	Illinois
United States	University of Colorado Cancer Center at UC Health Sciences Center	Aurora	Colorado
United States	St. Agnes Hospital Cancer Center	Baltimore	Maryland
United States	Good Shepherd Hospital	Barrington	Illinois
United States	Mary Bird Perkins Cancer Center - Baton Rouge	Baton Rouge	Louisiana
United States	Pennington Cancer Center at Baton Rouge General	Baton Rouge	Louisiana
United States	St. Francis Hospital and Health Centers - Beech Grove Campus	Beech Grove	Indiana
United States	MeritCare Bemidji	Bemidji	Minnesota
United States	Alta Bates Summit Comprehensive Cancer Center	Berkeley	California
United States	Billings Clinic - Downtown	Billings	Montana
United States	CCOP - Montana Cancer Consortium	Billings	Montana
United States	Northern Rockies Radiation Oncology Center	Billings	Montana
United States	Lurleen Wallace Comprehensive Cancer at University of Alabama - Birmingham	Birmingham	Alabama
United States	St. Joseph Medical Center	Bloomington	Illinois
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	Boston University Cancer Research Center	Boston	Massachusetts
United States	Tufts-NEMC Cancer Center	Boston	Massachusetts
United States	Boulder Community Hospital	Boulder	Colorado
United States	Ocean Medical Center at Meridian Health	Brick	New Jersey
United States	Maimonides Cancer Center at Maimonides Medical Center	Brooklyn	New York
United States	Roswell Park Cancer Institute	Buffalo	New York
United States	Peninsula Medical Center	Burlingame	California
United States	Lahey Clinic Medical Center - Burlington	Burlington	Massachusetts
United States	Fairview Ridges Hospital	Burnsville	Minnesota
United States	Radiation Oncology Centers - Cameron Park	Cameron Park	California
United States	Cancer Institute of Cape Girardeau, LLC	Cape Girardeau	Missouri
United States	Saint Francis Medical Center	Cape Girardeau	Missouri
United States	Southeast Missouri Regional Cancer Center at Southeast Missouri Hospital	Cape Girardeau	Missouri
United States	Mercy Cancer Center at Mercy San Juan Medical Center	Carmichael	California
United States	East Bay Radiation Oncology Center	Castro Valley	California
United States	Valley Medical Oncology Consultants - Castro Valley	Castro Valley	California
United States	Sandra L. Maxwell Cancer Center	Cedar City	Utah
United States	Hollings Cancer Center at Medical University of South Carolina	Charleston	South Carolina
United States	Presbyterian Cancer Center at Presbyterian Hospital	Charlotte	North Carolina
United States	Creticos Cancer Center at Advocate Illinois Masonic Medical Center	Chicago	Illinois
United States	John H. Stroger, Jr. Hospital of Cook County	Chicago	Illinois
United States	Rush University Medical Center	Chicago	Illinois
United States	University of Illinois Cancer Center	Chicago	Illinois
United States	Adena Regional Medical Center	Chillicothe	Ohio
United States	Charles M. Barrett Cancer Center at University Hospital	Cincinnati	Ohio
United States	Penrose Cancer Center at Penrose Hospital	Colorado Springs	Colorado
United States	CCOP - Columbus	Columbus	Ohio
United States	Doctors Hospital at Ohio Health	Columbus	Ohio
United States	Grant Medical Center Cancer Care	Columbus	Ohio
United States	Mount Carmel Health - West Hospital	Columbus	Ohio
United States	Riverside Methodist Hospital Cancer Care	Columbus	Ohio
United States	Cancer Care Center at John Muir Health - Concord Campus	Concord	California
United States	Dartmouth - Hitchcock Concord	Concord	New Hampshire
United States	Mercy and Unity Cancer Center at Mercy Hospital	Coon Rapids	Minnesota
United States	Bay Area Hospital	Coos Bay	Oregon
United States	Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas	Dallas	Texas
United States	Danville Regional Medical Center	Danville	Virginia
United States	Geisinger Cancer Institute at Geisinger Health	Danville	Pennsylvania
United States	Mercy Fitzgerald Hospital	Darby	Pennsylvania
United States	CCOP - Dayton	Dayton	Ohio
United States	David L. Rike Cancer Center at Miami Valley Hospital	Dayton	Ohio
United States	Good Samaritan Hospital	Dayton	Ohio
United States	Grandview Hospital	Dayton	Ohio
United States	Samaritan North Cancer Care Center	Dayton	Ohio
United States	Veterans Affairs Medical Center - Dayton	Dayton	Ohio
United States	Oakwood Cancer Center at Oakwood Hospital and Medical Center	Dearborn	Michigan
United States	Charles B. Eberhart Cancer Center at DeKalb Medical Center	Decatur	Georgia
United States	Decatur Memorial Hospital Cancer Care Institute	Decatur	Illinois
United States	Veterans Affairs Medical Center - Atlanta (Decatur)	Decatur	Georgia
United States	Grady Memorial Hospital	Delaware	Ohio
United States	Porter Adventist Hospital	Denver	Colorado
United States	Presbyterian - St. Luke's Medical Center	Denver	Colorado
United States	St. Joseph Hospital	Denver	Colorado
United States	Veterans Affairs Medical Center - Denver	Denver	Colorado
United States	Barbara Ann Karmanos Cancer Institute	Detroit	Michigan
United States	Josephine Ford Cancer Center at Henry Ford Hospital	Detroit	Michigan
United States	Good Samaritan Cancer Care Center at Advocate Good Samaritan Hospital	Downers Grove	Illinois
United States	City of Hope Comprehensive Cancer Center	Duarte	California
United States	CCOP - Duluth	Duluth	Minnesota
United States	Duluth Clinic Cancer Center - Duluth	Duluth	Minnesota
United States	Miller - Dwan Medical Center	Duluth	Minnesota
United States	St. Luke's Hospital Cancer Care Center	Duluth	Minnesota
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	CCOP - Hematology-Oncology Associates of Central New York	East Syracuse	New York
United States	Fairview Southdale Hospital	Edina	Minnesota
United States	Elkhart General Hospital	Elkhart	Indiana
United States	Swedish Medical Center	Englewood	Colorado
United States	Green Bay Oncology, Limited - Escanaba	Escanaba	Michigan
United States	CCOP - MeritCare Hospital	Fargo	North Dakota
United States	MeritCare Broadway	Fargo	North Dakota
United States	St. Francis Hospital	Federal Way	Washington
United States	Blanchard Valley Medical Associates	Findlay	Ohio
United States	Genesys Hurley Cancer Institute	Flint	Michigan
United States	Great Lakes Cancer Institute at McLaren Regional Medical Center	Flint	Michigan
United States	Hurley Medical Center	Flint	Michigan
United States	Poudre Valley Radiation Oncology	Fort Collins	Colorado
United States	Michael and Dianne Bienes Comprehensive Cancer Center at Holy Cross Hospital	Fort Lauderdale	Florida
United States	Brooke Army Medical Center	Fort Sam Houston	Texas
United States	Parkview Regional Cancer Center at Parkview Health	Fort Wayne	Indiana
United States	Radiation Oncology Associates Southwest	Fort Wayne	Indiana
United States	Middletown Regional Hospital	Franklin	Ohio
United States	Valley Medical Oncology	Fremont	California
United States	Mercy and Unity Cancer Center at Unity Hospital	Fridley	Minnesota
United States	Virginia K. Crosson Cancer Center at St. Jude Medical Center	Fullerton	California
United States	Northeast Georgia Medical Center	Gainesville	Georgia
United States	InterCommunity Cancer Center of Western Illinois	Galesburg	Illinois
United States	Charles R. Wood Cancer Center at Glens Falls Hospital	Glens Falls	New York
United States	Wayne Memorial Hospital, Incorporated	Goldsboro	North Carolina
United States	Wayne Radiation Oncology	Goldsboro	North Carolina
United States	Center for Cancer Care at Goshen General Hospital	Goshen	Indiana
United States	St. Mary's Regional Cancer Center at St. Mary's Hospital and Medical Center	Grand Junction	Colorado
United States	CCOP - Grand Rapids	Grand Rapids	Michigan
United States	Lacks Cancer Center at Saint Mary's Health Care	Grand Rapids	Michigan
United States	Three Rivers Community Hospital	Grants Pass	Oregon
United States	Great Falls Clinic - Main Facility	Great Falls	Montana
United States	North Colorado Medical Center	Greeley	Colorado
United States	Green Bay Oncology, Limited at St. Mary's Hospital	Green Bay	Wisconsin
United States	Green Bay Oncology, Limited at St. Vincent Hospital Regional Cancer Center	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	Marin Cancer Institute at Marin General Hospital	Greenbrae	California
United States	Sutter Health - Western Division Cancer Research Group	Greenbrae	California
United States	CCOP - Greenville	Greenville	South Carolina
United States	Leo W. Jenkins Cancer Center at ECU Medical School	Greenville	North Carolina
United States	Legacy Mount Hood Medical Center	Gresham	Oregon
United States	Van Elslander Cancer Center at St. John Hospital and Medical Center	Grosse Pointe Woods	Michigan
United States	Ingalls Cancer Care Center at Ingalls Memorial Hospital	Harvey	Illinois
United States	Pardee Memorial Hospital	Hendersonville	North Carolina
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	Independence Regional Health Center	Independence	Missouri
United States	Methodist Cancer Center at Methodist Hospital	Indianapolis	Indiana
United States	Dickinson County Healthcare System	Iron Mountain	Michigan
United States	Foote Memorial Hospital	Jackson	Michigan
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	Princeton Radiation Oncology Center	Jamesburg	New Jersey
United States	Joliet Oncology-Hematology Associates, Limited - West	Joliet	Illinois
United States	Ella Milbank Foshay Cancer Center at Jupiter Medical Center	Jupiter	Florida
United States	Borgess Medical Center	Kalamazoo	Michigan
United States	Bronson Methodist Hospital	Kalamazoo	Michigan
United States	West Michigan Cancer Center	Kalamazoo	Michigan
United States	CCOP - Kansas City	Kansas City	Missouri
United States	Kansas Masonic Cancer Research Institute at the University of Kansas Medical Center	Kansas City	Kansas
United States	North Kansas City Hospital	Kansas City	Missouri
United States	Parvin Radiation Oncology	Kansas City	Missouri
United States	Research Medical Center	Kansas City	Missouri
United States	Saint Luke's Cancer Institute at Saint Luke's Hospital	Kansas City	Missouri
United States	St. Joseph Medical Center	Kansas City	Missouri
United States	Truman Medical Center - Hospital Hill	Kansas City	Missouri
United States	Good Samaritan Cancer Center at Good Samaritan Hospital	Kearney	Nebraska
United States	Kingsbury Center for Cancer Care at Cheshire Medical Center	Keene	New Hampshire
United States	Charles F. Kettering Memorial Hospital	Kettering	Ohio
United States	Howard Community Hospital	Kokomo	Indiana
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	Center for Cancer Therapy at LaPorte Hospital and Health Services	La Porte	Indiana
United States	Wilford Hall Medical Center	Lackland Air Force Base	Texas
United States	Sparrow Regional Cancer Center	Lansing	Michigan
United States	CCOP - Nevada Cancer Research Foundation	Las Vegas	Nevada
United States	Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center	Lebanon	New Hampshire
United States	Lucille P. Markey Cancer Center at University of Kentucky	Lexington	Kentucky
United States	Liberty Hospital	Liberty	Missouri
United States	St. Rita's Medical Center	Lima	Ohio
United States	Arkansas Cancer Research Center at University of Arkansas for Medical Sciences	Little Rock	Arkansas
United States	St. Mary Mercy Hospital	Livonia	Michigan
United States	Sky Ridge Medical Center	Lone Tree	Colorado
United States	Hope Cancer Care Center at Longmont United Hospital	Longmont	Colorado
United States	USC/Norris Comprehensive Cancer Center and Hospital	Los Angeles	California
United States	James Graham Brown Cancer Center at University of Louisville	Louisville	Kentucky
United States	McKee Medical Center	Loveland	Colorado
United States	Joe Arrington Cancer Research and Treatment Center	Lubbock	Texas
United States	Lynchburg Hematology-Oncology Clinic	Lynchburg	Virginia
United States	Medical Center of Central Georgia	Macon	Georgia
United States	University of Wisconsin Paul P. Carbone Comprehensive Cancer Center	Madison	Wisconsin
United States	Elliot Regional Cancer Center at Elliot Hospital	Manchester	New Hampshire
United States	Minnesota Oncology Hematology, PA - Maplewood	Maplewood	Minnesota
United States	Kennestone Cancer Center at Wellstar Kennestone Hospital	Marietta	Georgia
United States	Strecker Cancer Center at Marietta Memorial Hospital	Marietta	Ohio
United States	Bay Area Cancer Care Center at Bay Area Medical Center	Marinette	Wisconsin
United States	Cardinal Bernardin Cancer Center at Loyola University Medical Center	Maywood	Illinois
United States	Dubs Cancer Center at Rogue Valley Medical Center	Medford	Oregon
United States	Providence Cancer Center at PMCC	Medford	Oregon
United States	Columbia Saint Mary's Hospital - Ozaukee	Mequon	Wisconsin
United States	University of Miami Sylvester Comprehensive Cancer Center - Miami	Miami	Florida
United States	CCOP - Mount Sinai Medical Center	Miami Beach	Florida
United States	Saint Anthony Memorial Health Centers	Michigan City	Indiana
United States	Upper Delaware Valley Cancer Center	Milford	Pennsylvania
United States	Columbia-Saint Mary's Cancer Care Center	Milwaukee	Wisconsin
United States	Medical College of Wisconsin Cancer Center	Milwaukee	Wisconsin
United States	Veterans Affairs Medical Center - Milwaukee	Milwaukee	Wisconsin
United States	Providence Milwaukie Hospital	Milwaukie	Oregon
United States	Virginia Piper Cancer Institute at Abbott - Northwestern Hospital	Minneapolis	Minnesota
United States	Memorial Medical Center	Modesto	California
United States	Jon and Karen Huntsman Cancer Center at Intermountain Medical Center	Murray	Utah
United States	Cancer Institute of New Jersey at UMDNJ - Robert Wood Johnson Medical School	New Brunswick	New Jersey
United States	Saint Peter's University Hospital	New Brunswick	New Jersey
United States	MBCCOP - LSU Health Sciences Center	New Orleans	Louisiana
United States	Medical Center of Louisiana - New Orleans	New Orleans	Louisiana
United States	St. Vincent's Comprehensive Cancer Center - Manhattan	New York	New York
United States	CCOP - Christiana Care Health Services	Newark	Delaware
United States	Licking Memorial Cancer Care Program at Licking Memorial Hospital	Newark	Ohio
United States	Sentara Cancer Institute at Sentara Norfolk General Hospital	Norfolk	Virginia
United States	BroMenn Regional Medical Center	Normal	Illinois
United States	Community Cancer Center	Normal	Illinois
United States	Alta Bates Summit Medical Center - Summit Campus	Oakland	California
United States	Bay Area Breast Surgeons, Incorporated	Oakland	California
United States	CCOP - Bay Area Tumor Institute	Oakland	California
United States	Larry G Strieff MD Medical Corporation	Oakland	California
United States	Tom K Lee, Incorporated	Oakland	California
United States	Green Bay Oncology, Limited - Oconto Falls	Oconto Falls	Wisconsin
United States	Val and Ann Browning Cancer Center at McKay-Dee Hospital Center	Ogden	Utah
United States	Oklahoma University Cancer Institute	Oklahoma City	Oklahoma
United States	Saint James Hospital and Health Centers Comprehensive Cancer Institute - Olympia Fields	Olympia Fields	Illinois
United States	Alegant Health Cancer Center at Bergan Mercy Medical Center	Omaha	Nebraska
United States	CCOP - Missouri Valley Cancer Consortium	Omaha	Nebraska
United States	Creighton University Medical Center	Omaha	Nebraska
United States	Immanuel Medical Center	Omaha	Nebraska
United States	Methodist Estabrook Cancer Center	Omaha	Nebraska
United States	Integrated Community Oncology Network - Orange Park	Orange Park	Florida
United States	M.D. Anderson Cancer Center at Orlando	Orlando	Florida
United States	Menorah Medical Center	Overland Park	Kansas
United States	Florida Cancer Center - Palatka	Palatka	Florida
United States	Bay Medical	Panama City	Florida
United States	Advocate Lutheran General Cancer Care Center	Park Ridge	Illinois
United States	Regional Cancer Center at Singing River Hospital	Pascagoula	Mississippi
United States	NSMC Cancer Center - Peabody	Peabody	Massachusetts
United States	Cancer Treatment Center at Pekin Hospital	Pekin	Illinois
United States	CCOP - Illinois Oncology Research Association	Peoria	Illinois
United States	Methodist Medical Center of Illinois	Peoria	Illinois
United States	Oncology Hematology Associates of Central Illinois, PC - Peoria	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	Kimmel Cancer Center at Thomas Jefferson University - Philadelphia	Philadelphia	Pennsylvania
United States	Valley Medical Oncology Consultants - Pleasanton	Pleasanton	California
United States	Mercy Regional Cancer Center at Mercy Hospital	Port Huron	Michigan
United States	Adventist Medical Center	Portland	Oregon
United States	CCOP - Columbia River Oncology Program	Portland	Oregon
United States	Legacy Emanuel Hospital and Health Center and Children's Hospital	Portland	Oregon
United States	Legacy Good Samaritan Hospital & Comprehensive Cancer Center	Portland	Oregon
United States	Oregon Health and Science University Cancer Institute	Portland	Oregon
United States	Providence Cancer Center at Providence Portland Medical Center	Portland	Oregon
United States	Providence St. Vincent Medical Center	Portland	Oregon
United States	Naval Medical Center - Portsmouth	Portsmouth	Virginia
United States	University Medical Center at Princeton	Princeton	New Jersey
United States	Miriam Hospital	Providence	Rhode Island
United States	Rhode Island Hospital Comprehensive Cancer Center	Providence	Rhode Island
United States	Utah Valley Regional Medical Center - Provo	Provo	Utah
United States	St. Mary - Corwin Regional Medical Center	Pueblo	Colorado
United States	Cancer Centers of North Carolina - Raleigh	Raleigh	North Carolina
United States	Rex Cancer Center at Rex Hospital	Raleigh	North Carolina
United States	Rapid City Regional Hospital	Rapid City	South Dakota
United States	McGlinn Family Regional Cancer Center at Reading Hospital and Medical Center	Reading	Pennsylvania
United States	St. Joseph Medical Center	Reading	Pennsylvania
United States	Reid Hospital & Health Care Services	Richmond	Indiana
United States	Veterans Affairs Medical Center - Richmond	Richmond	Virginia
United States	Virginia Commonwealth University Massey Cancer Center	Richmond	Virginia
United States	Southern Regional Medical Center	Riverdale	Georgia
United States	Hubert H. 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	Center for Cancer Care at OSF Saint Anthony Medical Center	Rockford	Illinois
United States	Swedish-American Regional Cancer Center	Rockford	Illinois
United States	Radiation Oncology Center - Roseville	Roseville	California
United States	William Beaumont Hospital - Royal Oak Campus	Royal Oak	Michigan
United States	Mercy General Hospital	Sacramento	California
United States	Radiological Associates of Sacramento Medical Group, Incorporated	Sacramento	California
United States	University of California Davis Cancer Center	Sacramento	California
United States	Seton Cancer Institute at Saint Mary's - Saginaw	Saginaw	Michigan
United States	Flagler Cancer Center	Saint Augustine	Florida
United States	Dixie Regional Medical Center - East Campus	Saint George	Utah
United States	Norris Cotton Cancer Center - North	Saint Johnsbury	Vermont
United States	Heartland Regional Medical Center	Saint Joseph	Missouri
United States	Lakeland Regional Cancer Care Center - St. Joseph	Saint Joseph	Michigan
United States	CCOP - St. Louis-Cape Girardeau	Saint Louis	Missouri
United States	David C. Pratt Cancer Center at St. John's Mercy	Saint Louis	Missouri
United States	Saint Louis University Cancer Center	Saint Louis	Missouri
United States	CCOP - Metro-Minnesota	Saint Louis Park	Minnesota
United States	Park Nicollet Cancer Center	Saint Louis Park	Minnesota
United States	United Hospital	Saint Paul	Minnesota
United States	Huntsman Cancer Institute at University of Utah	Salt Lake City	Utah
United States	LDS Hospital	Salt Lake City	Utah
United States	Utah Cancer Specialists at UCS Cancer Center	Salt Lake City	Utah
United States	California Pacific Medical Center - California Campus	San Francisco	California
United States	San Francisco General Hospital Medical Center	San Francisco	California
United States	UCSF Helen Diller Family Comprehensive Cancer Center	San Francisco	California
United States	Doctors Medical Center - San Pablo Campus	San Pablo	California
United States	Curtis and Elizabeth Anderson Cancer Institute at Memorial Health University Medical Center	Savannah	Georgia
United States	Nancy N. and J. C. Lewis Cancer and Research Pavilion at St. Joseph's/Candler	Savannah	Georgia
United States	Mayo Clinic Scottsdale	Scottsdale	Arizona
United States	St. Francis Cancer Center at St. Francis Medical Center	Shakopee	Minnesota
United States	Shawnee Mission Medical Center	Shawnee Mission	Kansas
United States	Feist-Weiller Cancer Center at Louisiana State University Health Sciences	Shreveport	Louisiana
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	CCOP - Northern Indiana CR Consortium	South Bend	Indiana
United States	Memorial Hospital of South Bend	South Bend	Indiana
United States	Providence Cancer Institute at Providence Hospital - Southfield Campus	Southfield	Michigan
United States	Frederick R. and Betty M. Smith Cancer Treatment Center	Sparta	New Jersey
United States	Valley Cancer Center	Spring Valley	Illinois
United States	Cancer Institute at St. John's Hospital	Springfield	Illinois
United States	CCOP - Cancer Research for the Ozarks	Springfield	Missouri
United States	Hulston Cancer Center at Cox Medical Center South	Springfield	Missouri
United States	Mercy Medical Center	Springfield	Ohio
United States	St. John's Regional Health Center	Springfield	Missouri
United States	Stanford Cancer Center	Stanford	California
United States	Green Bay Oncology, Limited - Sturgeon Bay	Sturgeon Bay	Wisconsin
United States	H. Lee Moffitt Cancer Center and Research Institute at University of South Florida	Tampa	Florida
United States	North Suburban Medical Center	Thornton	Colorado
United States	J. Phillip Citta Regional Cancer Center at Community Medical Center	Toms River	New Jersey
United States	Cotton-O'Neil Cancer Center	Topeka	Kansas
United States	Munson Medical Center	Traverse City	Michigan
United States	General Robert Huyser Cancer Center at David Grant Medical Center	Travis Air Force Base	California
United States	UVMC Cancer Care Center at Upper Valley Medical Center	Troy	Ohio
United States	Legacy Meridian Park Hospital	Tualatin	Oregon
United States	Carle Cancer Center at Carle Foundation Hospital	Urbana	Illinois
United States	CCOP - Carle Cancer Center	Urbana	Illinois
United States	Solano Radiation Oncology Center	Vacaville	California
United States	Sutter Solano Medical Center	Vallejo	California
United States	Southwest Washington Medical Center Cancer Center	Vancouver	Washington
United States	Cancer Institute of New Jersey at Cooper - Voorhees	Voorhees	New Jersey
United States	Ridgeview Medical Center	Waconia	Minnesota
United States	John Muir/Mt. Diablo Comprehensive Cancer Center	Walnut Creek	California
United States	St. John Macomb Hospital	Warren	Michigan
United States	Lombardi Comprehensive Cancer Center at Georgetown University Medical Center	Washington	District of Columbia
United States	Washington Cancer Institute at Washington Hospital Center	Washington	District of Columbia
United States	University of Wisconcin Cancer Center at Aspirus Wausau Hospital	Wausau	Wisconsin
United States	Precision Radiotherapy at University Pointe	West Chester	Ohio
United States	Mount Carmel St. Ann's Cancer Center	Westerville	Ohio
United States	Exempla Lutheran Medical Center	Wheat Ridge	Colorado
United States	Frank M. and Dorothea Henry Cancer Center at Geisinger Wyoming Valley Medical Center	Wilkes-Barre	Pennsylvania
United States	Wilmed Radiation Oncology Services	Wilson	North Carolina
United States	Forsyth Regional Cancer Center at Forsyth Medical Center	Winston-Salem	North Carolina
United States	Cancer Treatment Center	Wooster	Ohio
United States	Ruth G. McMillan Cancer Center at Greene Memorial Hospital	Xenia	Ohio
United States	York Cancer Center at Apple Hill Medical Center	York	Pennsylvania

Sponsors (3)

Lead Sponsor	Collaborator
Radiation Therapy Oncology Group	National Cancer Institute (NCI), NRG Oncology

Countries where clinical trial is conducted

United States,  Canada, 

References & Publications (3)

Ang KK, Zhang Q, Rosenthal DI, Nguyen-Tan PF, Sherman EJ, Weber RS, Galvin JM, Bonner JA, Harris J, El-Naggar AK, Gillison ML, Jordan RC, Konski AA, Thorstad WL, Trotti A, Beitler JJ, Garden AS, Spanos WJ, Yom SS, Axelrod RS. Randomized phase III trial of — View Citation

Schwartz DL, Harris J, Yao M, Rosenthal DI, Opanowski A, Levering A, Ang KK, Trotti AM, Garden AS, Jones CU, Harari P, Foote R, Holland J, Zhang Q, Le QT. Metabolic tumor volume as a prognostic imaging-based biomarker for head-and-neck cancer: pilot resul — View Citation

Truong MT, Zhang Q, Rosenthal DI, List M, Axelrod R, Sherman E, Weber R, Nguyen-Tân PF, El-Naggar A, Konski A, Galvin J, Schwartz D, Trotti A, Silverman C, Singh A, Godette K, Bonner JA, Jones CU, Garden AS, Shenouda G, Matthiesen C, Le QT, Bruner D. Qual — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-free Survival (PFS) (3-year Rate Reported)	Progression-free survival (PFS) is defined as time from randomization to date of local, regional, or distant disease progression, or death from any cause. Patients last known to be alive without progression are censored at the date of last contact. Three-year rates were estimated by the Kaplan-Meier method. Local or regional progression is defined as an estimated increase in the size of the tumor (product of the perpendicular diameters of the two largest dimensions) of greater than 25%, taking as reference the smallest value of all previous measurements or appearance of new areas of malignant disease. Distant progression is defined as clear evidence of distant metastases.	From randomization until 434 failures have occurred, approximately 5 years from start of study. (Patients are followed until death or study termination, whichever occurs first.)
Secondary	Overall Survival (OS) (3-year Rate Reported)	Overall survival is defined as time from randomization to date of death from any cause. Patients last known to be alive are censored at the date of last contact. Three-year rates were estimated by the Kaplan-Meier method.	From randomization until 434 failures have occurred, approximately 5 years from start of study. (Patients are followed until death or study termination, whichever occurs first.)
Secondary	Local-regional Failure (LRF) (3-year Rate Reported)	Local-regional failure is defined as time from randomization to date of failure (local or regional progression), or distant disease progression, or death from any cause. Patients last known to be alive without progression are censored at the date of last contact. Distant disease progression is considered a competing risk. Local or regional progression is defined as an estimated increase in the size of the tumor (product of the perpendicular diameters of the two largest dimensions) of greater than 25%, taking as reference the smallest value of all previous measurements or appearance of new areas of malignant disease. Distant progression is defined as clear evidence of distant metastases. Three-year rates were estimated by the cumulative incidence method.	From randomization until 434 failures have occurred, approximately 5 years from start of study. (Patients are followed until death or study termination, whichever occurs first.)
Secondary	Rate of Mucositis Toxicity = Grade 3	Grade 3 or higher Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 radiation mucositis definitely, probably, or possibly related to protocol treatment. 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 AE, Grade 2 Moderate AE, Grade 3 Severe AE, Grade 4 Life-threatening or disabling AE, Grade 5 Death related to AE.	From start of treatment until 434 failures have occurred, approximately 5 years from start of study. (Patients are followed until death or study termination, whichever occurs first.)
Secondary	Rate of Other Toxicity = Grade 3 (Not Mucositis)	Grade 3 or higher Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 other than radiation mucositis definitely, probably, or possibly related to protocol treatment. 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 AE, Grade 2 Moderate AE, Grade 3 Severe AE, Grade 4 Life-threatening or disabling AE, Grade 5 Death related to AE.	From start of treatment until 434 failures have occurred, approximately 5 years from start of study. (Patients are followed until death or study termination, whichever occurs first.)
Secondary	Rate of Patients Who Tolerated Treatment	A patient was considered to have tolerated treatment if radiation therapy was scored as per protocol or with acceptable variation, they received 2 cycles of cisplatin, and for arm 2, they received the initial dose of cetuximab and at least 5 weekly doses of cetuximab .	From start of treatment to end of treatment (6-7 weeks)
Secondary	Rate of Deaths = 30 Days After Discontinuation of Protocol Treatment	Patients who died during treatment or within 30 days after the end of treatment	From start of treatment to 30 days after the end of treatment
Secondary	Quality of Life as Measured by European Quality of Life Questionnaire (EQ-5D)	The EQ-5D is a 2-part self-assessment questionnaire. First part is 5 items (mobility, self care, usual activities, pain/discomfort, anxiety/depression) each with 3 problem levels (1-none, 2-moderate, 3-extreme). Health states are defined by the combination of the leveled responses to the 5 dimensions, generating 243 health states to which unconsciousness and death are added. The 2nd part is a visual analogue scale (VAS) valuing current health state, measured on a 20-cm 10-point interval scale. Worst imaginable health state is scored as 0 at the bottom of the scale, and best imaginable health state is scored as 100 at the top. Both the 5-item index score and the VAS score are transformed into a utility score between 0 (worst health state) and 1 (best health state).	3 months and 12 months
Secondary	Quality of Life as Measured by Proportion of Patients With Performance Status Scale for Head and Neck Cancer (PSS-HN) Scores = 50	The PSS-HN is a clinician rated instrument consisting of assessment of three functions (subscales): Normalcy of Diet, Eating in Public, and Understandability of Speech. The interviewer rates the patient on each scale based on the patient's responses to targeted questions. Scores on each subscale range from 0-100, with higher scores indicating better performance. It has been demonstrated to be reliable and valid in head and neck cancer patients.The site research nurse or clinical research associate (CRA) will determine the score on each of the subscales by performing a clinical evaluation and unstructured interview format. The PSS-HN takes approximately 5 minutes to complete.	3 months and 12 months
Secondary	Quality of Life as Measured by Change From Baseline in Functional Assessment of Cancer Therapy-General (FACT-HN) at 12 Months	The Functional Assessment of Cancer Therapy-Head and Neck (FACT-HN) is a 10-item self-report instrument designed to measure multidimensional quality of life in patients with head and neck cancer. It is to be administered with the FACT-General. There are 5 responses options, with 0=Not a lot and 4=Very much. All items are added together to obtain a total score which ranges from 0-40. Certain items must be reversed before it is added by subtracting the response from 4. It requires at least 50% of the items to be completed while the overall response rate of the FACT-HN including the FACT-G must be greater than 80%. If items are missing, the subscale scores can be prorated. A higher score indicated better QOL. Change from baseline to 12 months (12 months - baseline) is reported.	Baseline and 12 months
Secondary	Correlation of Expression of Epidermal Growth Factor Receptor (EGFR) With PFS, OS, and LRF	EGFR expression is categorized as high (>/=80%) and low (<80%) in order to compare outcome by favorable and unfavorable risk group, per protocol. Times are measured from randomization. Overall survival is defined as time from randomization to date of death from any cause. PFS is time to loco-regional progression (LRP), distant disease progression (DDP), or death. LRF is time to LRP, DDP, or death, with DDP considered a competing risk. Patients last known to be alive without event are censored at the date of last contact. LRP is defined as an estimated increase in the size of the tumor (product of the perpendicular diameters of the two largest dimensions) of greater than 25%, taking as reference the smallest value of all previous measurements or appearance of new areas of malignant disease. DDP is defined as clear evidence of distant metastases. Three-year LRF rates were estimated by the cumulative incidence method. Three-year PFS and OS rates were estimated by the Kaplan-Meier method.	From randomization until 434 failures have occurred, approximately 5 years from start of study. (Patients are followed until death or study termination, whichever occurs first.)
Secondary	Correlation of Pre-treatment Positron Emission Tomography (PET)/CT Maximum Standardized Uptake Value (SUVmax) With PFS, OS, and LRF	SUVmax is categorized as high (>median) and low (	From randomization until 434 failures have occurred, approximately 5 years from start of study. (Patients are followed until death or study termination, whichever occurs first.)
Secondary	2-year Nodal Relapse Rates in Clinical N2-3 Patients by Post-treatment PET/CT Finding and Nodal Response	Patients are grouped by the combination of clinical nodal response status and the post-treatment PET/CT finding (negative or positive). Nodal relapse rate is calculated for each group by the cumulative incidence method. Relapse is defined as reappearance of tumor after complete response. If possible, relapse should be confirmed by biopsy.	From randomization to 2 years