RT With or Without Cetuximab in Treating Patients Who Have Undergone Surgery for Locally Advanced Head and Neck Cancer

Head and Neck Cancer Clinical Trial

Official title:

A Phase III Study of Postoperative Radiation Therapy (IMRT) +/- Cetuximab for Locally-Advanced Resected Head and Neck Cancer

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT00956007
• Other study ID #: RTOG 0920
• Secondary ID: CDR0000651536NCI
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: March 31, 2010
• Est. completion date: August 2029

Study information

• Verified date: April 2024
• Source: Radiation Therapy Oncology Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

RATIONALE: Giving radiation therapy that uses a 3-dimensional (3-D) image of the tumor to help focus thin beams of radiation directly on the tumor, and giving radiation therapy in higher doses over a shorter period of time, may kill more tumor cells and have fewer side effects. 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 radiation therapy is more effective when given alone or together with cetuximab in treating patients with head and neck cancer that has been removed by surgery.

PURPOSE: This randomized phase III trial is studying radiation therapy to see how well it works compared with radiation therapy given together with cetuximab in treating patients who have undergone surgery for locally advanced head and neck cancer.

Description:

OBJECTIVES:

Primary

• Determine whether the addition of cetuximab to postoperative intensity-modulated radiotherapy (IMRT) will improve overall survival (OS) in patients with locally advanced squamous cell carcinoma of the head and neck at intermediate risk following surgery.

Secondary

• Assess the impact of the addition of cetuximab to postoperative IMRT on disease-free survival (DFS) of these patients.

• Assess the impact of the addition of cetuximab to postoperative IMRT on acute and late dysphagia, xerostomia, skin toxicity, and other toxicities according to common Toxicity Criteria for Adverse Effects (CTCAE), v. 4 and their relationships with patient-reported outcomes at 3, 12, and 24 months.

• Analyze tumor for epidermal growth factor receptor (EGFR), specifically the extent of EGFR overexpression by immuno-histochemistry (IHC) and Fluorescence in situ hybridization (FISH) analysis, EGFRvIII expression, as well as the association of these assay data with OS and DFS.

• Analyze tumor for human papillomavirus (HPV) infection (as defined by in situ hybridization), specifically, within the cohort of patients with oropharynx cancer, to perform an exploratory analysis of the impact of HPV on DFS and OS of this patient subset.

• Analyze tumor DNA for TP53 mutations as a predictor of response to cetuximab and prognosis.

• Analyze germline DNA of polymorphic variants in EGFR intron repeats as a predictor of response to cetuximab.

Tertiary

• Assess the impact of the addition of cetuximab to postoperative IMRT on loco-regional control.

• Assess the impact of the addition of cetuximab to postoperative IMRT on patient-reported quality of life, swallowing, xerostomia, and skin toxicity based on head and neck specific instruments, including the Performance Status Scale for Head and Neck Cancer (PSS-HN), the Functional Assessment of Cancer Therapy-Head & Neck (FACT-H&N), the University of Michigan Xerostomia-Related Quality of Life Scale (XeQOLS), and the Dermatology Life Quality Index (DLQI).

• Assess the impact of the addition of cetuximab to postoperative IMRT on cost-utility analysis using the EuroQol (EQ-5D).

• Evaluate the utility of image-guided radiotherapy (IGRT) as a means of enhancing the efficacy (i.e., loco-regional control) of IMRT while reducing the acute and/or late toxicity (particularly xerostomia) and improving patient-reported outcomes (particularly XeQOLS scores).

• Retrospectively compare the loco-regional control rate in patients treated with IMRT alone (no IGRT or cetuximab) with similar patients treated with external beam radiotherapy alone in the postoperative clinical trial Radiation Therapy Oncology Group (RTOG)-95 01.

OUTLINE: This is a multicenter study. Patients are stratified according to clinical stage (T1-3 vs T4a), EGFR expression (high [≥ 80% of cells staining positive] vs low [< 80% of cells staining positive] vs not evaluable), primary site of disease (oral cavity vs larynx vs oropharynx p16+ vs oropharynx p16- vs oropharynx, p16 not evaluable), and use of image-guided radiotherapy (yes vs no). Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients undergo intensity-modulated radiotherapy (IMRT) once daily 5 days a week for 6 weeks in the absence of disease progression or unacceptable toxicity.

• Arm II: Patients undergo IMRT as in arm I. Patients also receive cetuximab IV over 1-2 hours once weekly beginning at least 5 days prior to the start of IMRT and continuing for 4 weeks after the completion of IMRT (for a total of 11 doses) in the absence of disease progression or unacceptable toxicity.

Quality of life is assessed at baseline and at 3, 12, and 24 months.

Tissue samples are collected periodically for further laboratory analysis.

After completion of study treatment, patients are followed up at 1 and 3 months, every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.

Other known NCT identifiers

• NCT01311063

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 702
• Est. completion date: August 2029
• Est. primary completion date: September 5, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Conditions for Patient Eligibility:

• Pathologically (histologically) proven diagnosis of squamous cell carcinoma (including variants such as verrucous carcinoma, spindle cell carcinoma, carcinoma NOS [not otherwise specified], etc.) of the head/neck (oral cavity, oropharynx or larynx); Note: Hypopharynx primaries are excluded because these patients have both a poor prognosis and high likelihood of post- radiation complications.

• Clinical stage T1, N1-2 or T2-4a, N0-2, M0 including no distant metastases, based upon the following minimum diagnostic workup:

• General history and physical examination by a radiation oncologist and/or medical oncologist within 8 weeks prior to registration;

• Examination by an otolaryngologists or Head & Neck Surgeon, within 8 weeks prior to registration; a laryngopharyngoscopy (mirror and/or fiberoptic and/or direct procedure) is recommended but not required.

• Chest x-ray (at a minimum) or chest computed tomography (CT) scan (with or without contrast) or CT/positron emission tomography (PET) of chest (with or without contrast) within 8 weeks prior to registration.

• Gross total resection of the primary tumor with curative intent must be completed within 7 weeks of registration with surgical pathology demonstrating one or more of the following intermediate risk factors:

• Perineural invasion;

• Lymphovascular invasion;

• Single lymph node > 3 cm or = 2 lymph nodes (all < 6 cm) [no extracapsular extension];

• Close margin(s) of resection, defined as cancer extending to within 5 mm of a surgical margin, and/or an initially focally positive margin that is subsequently superseded by intraoperative negative margins. Similarly, patients whose tumors had focally positive margins in the main specimen but negative margins from re-excised samples in the region of the positive margin are eligible.

• Pathologically confirmed T3 or T4a primary tumor.

• T2 oral cavity cancer with > 5 mm depth of invasion.

• Zubrod Performance Status of 0-1 within 2 weeks prior to registration;

• Age = 18;

• Complete blood count (CBC)/differential obtained within 4 weeks prior to registration on study, with adequate bone marrow function defined as follows:

• Absolute granulocyte count (AGC) = 1,500 cells/mm3;

• Platelets = 100,000 cells/mm3;

• Hemoglobin (Hgb) = 8.0 g/dl (Note: The use of transfusion or other intervention to achieve Hgb =8.0 g/dl is acceptable).

• Adequate hepatic function, defined as follows:

• Total bilirubin < 2 x institutional upper limit of normal (ULN) within 2 weeks prior to registration;

• aspartate aminotransferase (AST) or alanine transaminase (ALT) < 3 x institutional ULN within 2 weeks prior to registration.

• Adequate renal function, defined as follows:

• Serum creatinine (Scr) < 2 x institutional ULN within 2 weeks prior to registration or; 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 (weight in kg)] /[(SCr mg/dl) x (72)] CCr female = 0.85 x (CCr male)

• Negative serum pregnancy test within 2 weeks prior to registration for women of childbearing potential;

• The following assessments are required within 2 weeks prior to the start of registration:

Na, K, Cl, glucose, Ca, Mg, and albumin. Note: Patients with an initial magnesium < 0.5 mmol/L (1.2 mg/dl) may receive corrective magnesium supplementation but should continue to receive either prophylactic weekly infusion of magnesium and/or oral magnesium supplementation (e.g., magnesium oxide) at the investigator's discretion.

• Women of childbearing potential and male participants who are sexually active must agree to use a medically effective means of birth control;

• Patients must provide study specific informed consent prior to study entry, including consent for mandatory tissue submission for EGFR and for oropharyngeal patients, HPV analyses.

Conditions for Patient Ineligibility

• Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for a minimum of 3 years; noninvasive cancers (For example, carcinoma in situ of the breast, oral cavity, or cervix are all permissible) are permitted even if diagnosed and treated < 3 years ago. Patients with simultaneous primaries or bilateral tumors are excluded, with the exception of patients with bilateral tonsil cancers or patients with T1-2, N0, M0 resected differentiated thyroid carcinoma, who are eligible.

• Per the operative and/or pathology report, positive margin(s) [defined as tumor present at the cut or inked edge of the tumor], nodal extracapsular extension, and/or gross residual disease after surgery; Note: Patients whose tumors had focally positive margins in the main specimen but negative margins from re-excised samples in the region of the positive margin are eligible.

• Prior systemic chemotherapy or anti-EGF therapy for the study cancer; note: prior chemotherapy or anti-EGF therapy for a different cancer is allowable.

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

• Severe, active co-morbidity, defined as follows:

• Unstable angina and/or congestive heart failure requiring hospitalization within 6 months prior to registration;

• Transmural myocardial infarction within 6 months prior to registration;

• 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;

• Idiopathic pulmonary fibrosis or other severe interstitial lung disease that requires oxygen therapy or is thought to require oxygen therapy within 1 year prior to registration;

• Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects; note, however, that laboratory tests for coagulation parameters are not required for entry into this protocol.

• Acquired Immune Deficiency Syndrome (AIDS) based upon current Centers for Disease Control and Prevention (CDC) definition; note: 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.

• Grade 3-4 electrolyte abnormalities (CTCAE v4):

• Serum calcium (ionized or adjusted for albumin) < 7 mg/dl (1.75 mmol/L) or >12.5 mg/dl (> 3.1 mmol/L) despite intervention to normalize levels;

• Glucose < 40 mg/dl (< 2.2 mmol/L) or > 250 mg/dl (> 14mmol/L);

• Magnesium < 0.9 mg/dl (< 0.4 mmol/L) or > 3 mg/dl (> 1.23 mmol/L) despite intervention to normalize levels;

• Potassium < 3.0 mmol/L or > 6 mmol/L despite intervention to normalize levels;

• Sodium < 130 mmol/L or > 155 mmol/L despite intervention to normalize levels.

• 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.

• Prior allergic reaction to cetuximab.

Related Conditions & MeSH terms

• Head and Neck Cancer
• Head and Neck Neoplasms

Intervention

Biological:
• cetuximab
intravenously

Radiation:
• intensity-modulated radiation therapy
daily fractions

Locations

Country	Name	City	State
Canada	Cross Cancer Institute	Edmonton	Alberta
Canada	London Regional Cancer Program	London	Ontario
Canada	CHUM - Hopital Notre-Dame	Montreal	Quebec
Canada	McGill University Department of Oncology	Montreal	Quebec
Canada	Ottawa Health Research Institute-General Division	Ottawa	Ontario
Canada	CHUQ - Pavilion Hotel-Dieu de Quebec	Quebec City	Quebec
Canada	Allan Blair Cancer Centre	Regina	Saskatchewan
Canada	Centre Hospitalier Universitaire de Sherbrooke-Fleurimont	Sherbrooke	Quebec
Canada	Doctor H. Bliss Murphy Cancer Centre	St. John's	Newfoundland and Labrador
Canada	Health Sciences North	Sudbury	Ontario
Canada	University Health Network-Princess Margaret Hospital	Toronto	Ontario
Canada	CancerCare Manitoba	Winnipeg	Manitoba
China	Chinese University of Hong Kong-Prince of Wales Hospital	Shatin	Hong Kong
Saudi Arabia	King Faisal Specialist Hospital and Research Centre	Riyadh
United States	Akron General Medical Center	Akron	Ohio
United States	Summa Akron City Hospital/Cooper Cancer Center	Akron	Ohio
United States	New York Oncology Hematology PC - Albany	Albany	New York
United States	University of New Mexico	Albuquerque	New Mexico
United States	Lehigh Valley Hospital	Allentown	Pennsylvania
United States	McFarland Clinic PC-William R Bliss Cancer Center	Ames	Iowa
United States	AnMed Health Cancer Center	Anderson	South Carolina
United States	Saint Joseph Mercy Hospital	Ann Arbor	Michigan
United States	University of Michigan	Ann Arbor	Michigan
United States	Langlade Hospital and Cancer Center	Antigo	Wisconsin
United States	Fox Valley Hematology and Oncology	Appleton	Wisconsin
United States	Mission Hospital-Memorial Campus	Asheville	North Carolina
United States	Emory University/Winship Cancer Institute	Atlanta	Georgia
United States	Sutter Cancer Centers Radiation Oncology Services-Auburn	Auburn	California
United States	Rocky Mountain Cancer Centers-Aurora	Aurora	Colorado
United States	University of Colorado Cancer Center - Anschutz Cancer Pavilion	Aurora	Colorado
United States	Texas Oncology - Central Austin Cancer Center	Austin	Texas
United States	Texas Oncology - South Austin Cancer Center	Austin	Texas
United States	Texas Oncology-Austin Midtown	Austin	Texas
United States	University of Maryland/Greenebaum Cancer Center	Baltimore	Maryland
United States	Summa Barberton Hospital	Barberton	Ohio
United States	Memorial Sloan Kettering Cancer Center at Basking Ridge	Basking Ridge	New Jersey
United States	Mary Bird Perkins Cancer Center	Baton Rouge	Louisiana
United States	Texas Oncology PA - Bedford	Bedford	Texas
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	Saint Alphonsus Regional Medical Center	Boise	Idaho
United States	Boston Medical Center	Boston	Massachusetts
United States	Tufts Medical Center	Boston	Massachusetts
United States	Harrison Medical Center	Bremerton	Washington
United States	Saint Vincent's Medical Center	Bridgeport	Connecticut
United States	Maimonides Medical Center	Brooklyn	New York
United States	Lahey Hospital and Medical Center	Burlington	Massachusetts
United States	Cooper Hospital University Medical Center	Camden	New Jersey
United States	Sutter Cancer Centers Radiation Oncology Services-Cameron Park	Cameron Park	California
United States	Sands Cancer Center	Canandaigua	New York
United States	Mercy Medical Center	Canton	Ohio
United States	Cape Radiation Oncology	Cape Girardeau	Missouri
United States	Mercy San Juan Medical Center	Carmichael	California
United States	University of North Carolina	Chapel Hill	North Carolina
United States	Geaugra Hospital	Chardon	Ohio
United States	Medical University of South Carolina	Charleston	South Carolina
United States	University of Virginia	Charlottesville	Virginia
United States	John H Stroger Jr Hospital of Cook County	Chicago	Illinois
United States	University of Illinois	Chicago	Illinois
United States	University of Cincinnati	Cincinnati	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	University of Missouri - Ellis Fischel	Columbia	Missouri
United States	Ohio State University Medical Center	Columbus	Ohio
United States	Memorial Sloan Kettering Cancer Center Commack	Commack	New York
United States	Mercy Hospital	Coon Rapids	Minnesota
United States	University of Texas Southwestern Medical Center	Dallas	Texas
United States	Geisinger Medical Center	Danville	Pennsylvania
United States	Oakwood Hospital	Dearborn	Michigan
United States	Atlanta VA Medical Center	Decatur	Georgia
United States	University of Miami Sylvester Comprehensive Cancer Center at Deerfield Beach	Deerfield Beach	Florida
United States	Texas Oncology-Denton South	Denton	Texas
United States	Porter Adventist Hospital	Denver	Colorado
United States	Iowa Methodist Medical Center	Des Moines	Iowa
United States	Mercy Medical Center - Des Moines	Des Moines	Iowa
United States	Henry Ford Hospital	Detroit	Michigan
United States	Saint John Hospital and Medical Center	Detroit	Michigan
United States	Wayne State University/Karmanos Cancer Institute	Detroit	Michigan
United States	City of Hope	Duarte	California
United States	Saint Luke's Hospital of Duluth	Duluth	Minnesota
United States	Northeast Radiation Oncology Center	Dunmore	Pennsylvania
United States	Pocono Medical Center	East Stroudsburg	Pennsylvania
United States	Mercy Cancer Center-Elyria	Elyria	Ohio
United States	Swedish Medical Center	Englewood	Colorado
United States	Willamette Valley Cancer Center	Eugene	Oregon
United States	NorthShore University HealthSystem-Evanston Hospital	Evanston	Illinois
United States	Exeter Hospital	Exeter	New Hampshire
United States	Roger Maris Cancer Center	Fargo	North Dakota
United States	Parkview Hospital Randallia	Fort Wayne	Indiana
United States	Radiation Oncology Associates PC	Fort Wayne	Indiana
United States	The Klabzuba Cancer Center	Fort Worth	Texas
United States	Unity Hospital	Fridley	Minnesota
United States	Northeast Georgia Medical Center	Gainesville	Georgia
United States	Adams Cancer Center	Gettysburg	Pennsylvania
United States	Wayne Radiation Oncology	Goldsboro	North Carolina
United States	Saint Vincent Hospital	Green Bay	Wisconsin
United States	Greenville Health System Cancer Institute-Faris	Greenville	South Carolina
United States	Greenville Health System Cancer Institute/Greenville CCOP	Greenville	South Carolina
United States	Gibbs Cancer Center-Pelham	Greer	South Carolina
United States	Sentara Cancer Institute at Sentara CarePlex Hospital	Hampton	Virginia
United States	Cherry Tree Cancer Center	Hanover	Pennsylvania
United States	Ingalls Memorial Hospital	Harvey	Illinois
United States	Hines Veterans Administration Hospital	Hines	Illinois
United States	Queen's Medical Center	Honolulu	Hawaii
United States	The Cancer Center of Hawaii-Liliha	Honolulu	Hawaii
United States	University of Hawaii	Honolulu	Hawaii
United States	Ben Taub General Hospital	Houston	Texas
United States	M D Anderson Cancer Center	Houston	Texas
United States	Memorial Hermann Memorial City Medical Center	Houston	Texas
United States	Cleveland Clinic Cancer Center Independence	Independence	Ohio
United States	Community Regional Cancer Care-East Radiation Oncology	Indianapolis	Indiana
United States	Community Regional Cancer Care-North	Indianapolis	Indiana
United States	IU Health Methodist Hospital	Indianapolis	Indiana
United States	University of Iowa Hospitals and Clinics	Iowa City	Iowa
United States	University of Mississippi Medical Center	Jackson	Mississippi
United States	Mayo Clinic in Florida	Jacksonville	Florida
United States	West Michigan Cancer Center	Kalamazoo	Michigan
United States	Kansas City Cancer Centers - North	Kansas City	Missouri
United States	University of Kansas Medical Center	Kansas City	Kansas
United States	Tri-Cities Cancer Center	Kennewick	Washington
United States	Wellmont Holston Valley Hospital and Medical Center	Kingsport	Tennessee
United States	Kinston Medical Specialists PA	Kinston	North Carolina
United States	Gundersen Lutheran	La Crosse	Wisconsin
United States	UC San Diego Moores Cancer Center	La Jolla	California
United States	Saint Mary Medical and Regional Cancer Center	Langhorne	Pennsylvania
United States	Dartmouth Hitchcock Medical Center	Lebanon	New Hampshire
United States	Kansas City Cancer Center-Lee's Summit	Lee's Summit	Missouri
United States	Central Maine Medical Center	Lewiston	Maine
United States	University of Kentucky	Lexington	Kentucky
United States	Saint Elizabeth Regional Medical Center	Lincoln	Nebraska
United States	Rocky Mountain Cancer Centers-Littleton	Littleton	Colorado
United States	Kaiser Permanente Los Angeles Medical Center	Los Angeles	California
United States	Los Angeles County-USC Medical Center	Los Angeles	California
United States	University of Southern California/Norris Cancer Center	Los Angeles	California
United States	The James Graham Brown Cancer Center at University of Louisville	Louisville	Kentucky
United States	University of Wisconsin Hospital and Clinics	Madison	Wisconsin
United States	Minnesota Oncology Hematology PA-Maplewood	Maplewood	Minnesota
United States	Bay Area Medical Center	Marinette	Wisconsin
United States	Hillcrest Hospital Cancer Center	Mayfield Heights	Ohio
United States	Loyola University Medical Center	Maywood	Illinois
United States	Summa Health Center at Lake Medina	Medina	Ohio
United States	Lake University Ireland Cancer Center	Mentor	Ohio
United States	Baptist Hospital of Miami	Miami	Florida
United States	University of Miami Miller School of Medicine-Sylvester Cancer Center	Miami	Florida
United States	Southwest General Health Center Ireland Cancer Center	Middleburg Heights	Ohio
United States	Clement J. Zablocki VA Medical Center	Milwaukee	Wisconsin
United States	Froedtert and the Medical College of Wisconsin	Milwaukee	Wisconsin
United States	Memorial Medical Center	Modesto	California
United States	West Virginia University Healthcare	Morgantown	West Virginia
United States	Fox Chase Cancer Center at Virtua Memorial Hospital of Burlington County	Mount Holly	New Jersey
United States	Skagit Valley Hospital	Mount Vernon	Washington
United States	IU Health Ball Memorial Hospital	Muncie	Indiana
United States	Intermountain Medical Center	Murray	Utah
United States	Vanderbilt-Ingram Cancer Center	Nashville	Tennessee
United States	Saint Peter's University Hospital	New Brunswick	New Jersey
United States	Yale University	New Haven	Connecticut
United States	Touro Infirmary	New Orleans	Louisiana
United States	Tulane University Health Sciences Center	New Orleans	Louisiana
United States	Beth Israel Medical Center	New York	New York
United States	Memorial Sloan-Kettering Cancer Center	New York	New York
United States	Christiana Care Health System-Christiana Hospital	Newark	Delaware
United States	UMDNJ - New Jersey Medical School	Newark	New Jersey
United States	Sentara Hospitals	Norfolk	Virginia
United States	William Backus Hospital	Norwich	Connecticut
United States	Bay Area Tumor Institute CCOP	Oakland	California
United States	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma
United States	Nebraska Methodist Hospital	Omaha	Nebraska
United States	The Nebraska Medical Center	Omaha	Nebraska
United States	UHHS-Chagrin Highlands Medical Center	Orange Village	Ohio
United States	Saint Charles Hospital	Oregon	Ohio
United States	Florida Hospital	Orlando	Florida
United States	UF Cancer Center at Orlando Health	Orlando	Florida
United States	Singing River Hospital	Pascagoula	Mississippi
United States	Albert Einstein Medical Center	Philadelphia	Pennsylvania
United States	Fox Chase Cancer Center	Philadelphia	Pennsylvania
United States	Thomas Jefferson University Hospital	Philadelphia	Pennsylvania
United States	University of Pennsylvania/Abramson Cancer Center	Philadelphia	Pennsylvania
United States	Pomona Valley Hospital Medical Center	Pomona	California
United States	Oregon Health and Science University	Portland	Oregon
United States	Portland Veterans Administration Medical Center	Portland	Oregon
United States	Providence Portland Medical Center	Portland	Oregon
United States	Providence Saint Vincent Medical Center	Portland	Oregon
United States	Western Oncology Research Consortium	Portland	Oregon
United States	Cancer Centers of North Carolina	Raleigh	North Carolina
United States	Rapid City Regional Hospital	Rapid City	South Dakota
United States	Robinson Radiation Oncology	Ravenna	Ohio
United States	Renown Regional Medical Center	Reno	Nevada
United States	Hunter Holmes McGuire Veterans Administration Medical Center	Richmond	Virginia
United States	Virginia Commonwealth University	Richmond	Virginia
United States	Highland Hospital	Rochester	New York
United States	Mayo Clinic	Rochester	Minnesota
United States	University of Rochester	Rochester	New York
United States	University Radiation Oncology	Rochester	New York
United States	Memorial Sloan-Kettering Cancer Center Rockville Centre	Rockville Centre	New York
United States	Sutter Cancer Centers Radiation Oncology Services-Roseville	Roseville	California
United States	The Permanente Medical Group-Roseville Radiation Oncology	Roseville	California
United States	Texas Oncology - Round Rock Cancer Center	Round Rock	Texas
United States	Texas Oncology-Seton Williamson	Round Rock	Texas
United States	Mercy General Hospital Radiation Oncology Center	Sacramento	California
United States	Sutter General Hospital	Sacramento	California
United States	University of California at Davis Cancer Center	Sacramento	California
United States	Saint Mary's of Michigan	Saginaw	Michigan
United States	Dixie Medical Center Regional Cancer Center	Saint George	Utah
United States	Saint Helena Hospital	Saint Helena	California
United States	Barnes-Jewish West County Hospital	Saint Louis	Missouri
United States	Missouri Baptist Medical Center	Saint Louis	Missouri
United States	Saint John's Mercy Medical Center	Saint Louis	Missouri
United States	Saint Louis University Hospital	Saint Louis	Missouri
United States	Siteman Cancer Center-South County	Saint Louis	Missouri
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	Regions Hospital	Saint Paul	Minnesota
United States	Siteman Cancer Center - Saint Peters	Saint Peters	Missouri
United States	Salem Hospital	Salem	Oregon
United States	Peninsula Regional Medical Center	Salisbury	Maryland
United States	Huntsman Cancer Institute/University of Utah	Salt Lake City	Utah
United States	LDS Hospital	Salt Lake City	Utah
United States	Utah Cancer Specialists-Salt Lake City	Salt Lake City	Utah
United States	Cancer Care Centers of South Texas- Northeast	San Antonio	Texas
United States	University of Texas Health Science Center at San Antonio	San Antonio	Texas
United States	UCSF-Mount Zion	San Francisco	California
United States	North Coast Cancer Care	Sandusky	Ohio
United States	Kaiser Permanente Medical Center - Santa Clara	Santa Clara	California
United States	Memorial Health University Medical Center	Savannah	Georgia
United States	Saint Joseph's-Candler Health System	Savannah	Georgia
United States	University of Washington Medical Center	Seattle	Washington
United States	Texas Cancer Center-Sherman	Sherman	Texas
United States	Siouxland Hematology Oncology Associates	Sioux City	Iowa
United States	Sanford Cancer Center-Oncology Clinic	Sioux Falls	South Dakota
United States	Memorial Sloan-Kettering Cancer Center at Sleepy Hallow	Sleepy Hollow	New York
United States	Sparta Cancer Treatment Center	Sparta	New Jersey
United States	Greenville Health System Cancer Institute-Spartanburg	Spartanburg	South Carolina
United States	Spartanburg Regional Medical Center	Spartanburg	South Carolina
United States	Cancer Care Northwest - Spokane South	Spokane	Washington
United States	Cancer Care Northwest-North Spokane	Spokane	Washington
United States	CoxHealth South Hospital	Springfield	Missouri
United States	Memorial Medical Center	Springfield	Illinois
United States	Mercy Hospital Springfield	Springfield	Missouri
United States	Saint John's Hospital	Springfield	Illinois
United States	Stanford University Hospitals and Clinics	Stanford	California
United States	Cleveland Clinic Cancer Center-Strongsville	Strongsville	Ohio
United States	Door County Cancer Center	Sturgeon Bay	Wisconsin
United States	Texas Oncology Cancer Center Sugar Land	Sugar Land	Texas
United States	Flower Hospital	Sylvania	Ohio
United States	Northwest CCOP	Tacoma	Washington
United States	Arizona Oncology Associates-West Orange Grove	Tucson	Arizona
United States	Carle Cancer Center	Urbana	Illinois
United States	Sutter Cancer Centers Radiation Oncology Services-Vacaville	Vacaville	California
United States	Compass Oncology Vancouver	Vancouver	Washington
United States	PeaceHealth Southwest Medical Center	Vancouver	Washington
United States	Sentara Virginia Beach General Hospital	Virginia Beach	Virginia
United States	MD Anderson Cancer Center at Cooper-Voorhees	Voorhees	New Jersey
United States	Saint John Macomb-Oakland Hospital	Warren	Michigan
United States	Aspirus Regional Cancer Center	Wausau	Wisconsin
United States	Wenatchee Valley Medical Center	Wenatchee	Washington
United States	University Pointe	West Chester	Ohio
United States	Reading Hospital	West Reading	Pennsylvania
United States	UHHS-Westlake Medical Center	Westlake	Ohio
United States	Wheeling Hospital	Wheeling	West Virginia
United States	Texas Oncology-Wichita Falls Texoma Cancer Center	Wichita Falls	Texas
United States	Wake Forest University Health Sciences	Winston-Salem	North Carolina
United States	Cleveland Clinic Wooster Specialty Center	Wooster	Ohio
United States	WellSpan Health-York Hospital	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,  China,  Saudi Arabia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Xerostomia as Measured by University of Michigan Xerostomia-Related Quality of Life Scale (XeQOLS) at Baseline and at 3, 12, and 24 Months		From randomization to 2 years.
Other	Swallowing as Measured by the Normalcy of Diet Subscale of the Performance Status Scale for Head and Neck Cancer (PSS-HN) at Baseline and at 3, 12, and 24 Months		From randomization to 2 years.
Other	Skin Toxicity as Measured by the Dermatology Life Quality Index (DLQI) at Baseline and at 3, 12, and 24 Months		From randomization to 2 years.
Other	Quality of Life as Measured by Functional Assessment of Cancer Therapy-Head & Neck (FACT-HN) and EuroQol (EQ-5D) at Baseline and at 3, 12, and 24 Months		From randomization to 2 years.
Other	Loco-regional Control		From randomization to date of failure (local or regional progression or distant progression or death) or last follow-up. Analysis occurs at the same time as the primary outcome.
Primary	Percentage of Participants Alive (Overall Survival)	Overall survival time is defined as time from registration/randomization to the date of death from any cause or last known follow-up (censored). Overall survival rates are estimated by the Kaplan-Meier method. Analysis occurred after all participants had potentially been on study for at least 5 years. The distributions of survival times are compared, which is reported in the statistical analysis results. Five-year rates are provided.	From randomization to date of death or last follow-up. Maximum follow-up at time of analysis was 12.1 years.
Secondary	Percentage of Participants With = Grade 3 Acute Dysphagia, Dry Mouth, or Skin Toxicity Related to Protocol Treatment	Common Terminology Criteria for Adverse Events (version 4.0) grades adverse event severity from 1=mild to 5=death. Adverse events (AEs) assessed to be definitely, probably, or possibly related to protocol treatment were included. If relationship was missing, it was assumed to be definitely, probably, or possibly related to protocol treatment. Acute adverse events are those occurring within 90 days of the start of radiation therapy.	From start of radiation therapy to 90 days
Secondary	Percentage of Participants With Other = Grade 3 Adverse Events Related to Protocol Treatment	Adverse events other than dysphagia, dermatitis radiation, and rash acneiform. Common Terminology Criteria for Adverse Events (version 4.0) grades adverse event severity from 1=mild to 5=death. Adverse events (AEs) assessed to be definitely, probably, or possibly related to protocol treatment were included. If relationship was missing, it was assumed to be definitely, probably, or possibly related to protocol treatment. Acute adverse events are those occurring within 90 days of the start of radiation therapy.	From start of radiation therapy to 90 days.
Secondary	Percentage of Participants With = Grade 3 Late Dysphagia, Dry Mouth, or Skin Toxicity Related to Protocol Treatment	Common Terminology Criteria for Adverse Events (version 4.0) grades adverse event severity from 1=mild to 5=death. Adverse events assessed to be definitely, probably, or possibly related to protocol treatment were included. If relationship was missing, it was assumed to be definitely, probably, or possibly related to protocol treatment. Late adverse events are those occurring after days from the start of radiation therapy.	From 91 days after start of radiation therapy to date of last reported follow-up. Maximum follow-up at time of analysis was 12.1 years.
Secondary	Percentage of Participants With Other = Grade 3 Late Adverse Events Related to Protocol Treatment	Adverse events other than dysphagia, dermatitis radiation, and rash acneiform. Common Terminology Criteria for Adverse Events (version 4.0) grades adverse event severity from 1=mild to 5=death. Adverse events (AEs) assessed to be definitely, probably, or possibly related to protocol treatment were included. If relationship was missing, it was assumed to be definitely, probably, or possibly related to protocol treatment. Late adverse events are those occurring after days from the start of radiation therapy.	From 91 days after start of radiation therapy to date of last reported follow-up. Maximum follow-up at time of analysis was 12.1 years.
Secondary	Disease-free Survival	Disease is defined as local-regional progression/recurrence (LRR) or distant metastasis (DM). LRR is defined as recurrent cancer in the tumor bed and/or neck not clearly attributable to a second primary neoplasm; both imaging and biopsy confirmation are strongly recommended. DM is defined as clear evidence of distant metastases; biopsy is recommended where possible. Disease-free survival time is defined as time from randomization to the date of first disease, death, or last known follow-up (censored), whichever occurred first. Disease-free survival rates are estimated using the Kaplan-Meier method. Analysis occurred after all participants had potentially been on study for at least 5 years. The distributions of disease-free survival times are compared, which is reported in the statistical analysis results. Five-year rates are provided.	From randomization to date of LRR, DM, death or last known follow-up, whichever occurred first. Maximum follow-up at time of analysis was 12.1 years.