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

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Head and Neck Cancer
• Intervention / Treatment: Biological: cetuximab; Radiation: intensity-modulated radiation therapy

Detailed 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 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 (T2-3 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.

• Study Type: Interventional
• Enrollment (Actual): 703
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 1Z2
      • Cross Cancer Institute
  • Manitoba
    • Winnipeg, Manitoba, Canada, R3E 0V9
      • CancerCare Manitoba
  • Newfoundland and Labrador
    • St. John's, Newfoundland and Labrador, Canada, A1B 3V6
      • Doctor H. Bliss Murphy Cancer Centre
  • Ontario
    • London, Ontario, Canada, N6A 4L6
      • London Regional Cancer Program
    • Ottawa, Ontario, Canada, K1H 1C4
      • Ottawa Health Research Institute-General Division
    • Sudbury, Ontario, Canada, P3E 5J1
      • Health Sciences North
    • Toronto, Ontario, Canada, M5G 2M9
      • University Health Network-Princess Margaret Hospital
  • Quebec
    • Montreal, Quebec, Canada, H2L 4M1
      • CHUM - Hopital Notre-Dame
    • Montreal, Quebec, Canada, H2W 1S6
      • McGill University Department of Oncology
    • Quebec City, Quebec, Canada, G1R 2J6
      • CHUQ - Pavilion Hotel-Dieu de Quebec
    • Sherbrooke, Quebec, Canada, J1H 5N4
      • Centre Hospitalier Universitaire de Sherbrooke-Fleurimont
  • Saskatchewan
    • Regina, Saskatchewan, Canada, S4T 7T1
      • Allan Blair Cancer Centre
• China
  • Hong Kong
    • Shatin, Hong Kong, China, OX1 3UJ
      • Chinese University of Hong Kong-Prince of Wales Hospital
• Saudi Arabia
  • Riyadh, Saudi Arabia, 11211
    • King Faisal Specialist Hospital and Research Centre
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • University of Alabama at Birmingham
  • Arizona
    • Tucson, Arizona, United States, 85704
      • Arizona Oncology Associates-West Orange Grove
  • California
    • Auburn, California, United States, 95603
      • Sutter Cancer Centers Radiation Oncology Services-Auburn
    • Cameron Park, California, United States, 95682
      • Sutter Cancer Centers Radiation Oncology Services-Cameron Park
    • Carmichael, California, United States, 95608
      • Mercy San Juan Medical Center
    • Duarte, California, United States, 91010
      • City of Hope
    • La Jolla, California, United States, 92093
      • UC San Diego Moores Cancer Center
    • Los Angeles, California, United States, 90033
      • Los Angeles County-USC Medical Center
    • Los Angeles, California, United States, 90027
      • Kaiser Permanente Los Angeles Medical Center
    • Los Angeles, California, United States, 90033
      • University of Southern California/Norris Cancer Center
    • Modesto, California, United States, 95355
      • Memorial Medical Center
    • Oakland, California, United States, 94609
      • Bay Area Tumor Institute CCOP
    • Pomona, California, United States, 91767
      • Pomona Valley Hospital Medical Center
    • Roseville, California, United States, 95678
      • The Permanente Medical Group-Roseville Radiation Oncology
    • Roseville, California, United States, 95661
      • Sutter Cancer Centers Radiation Oncology Services-Roseville
    • Sacramento, California, United States, 95817
      • University of California at Davis Cancer Center
    • Sacramento, California, United States, 95816
      • Sutter General Hospital
    • Sacramento, California, United States, 95819
      • Mercy General Hospital Radiation Oncology Center
    • Saint Helena, California, United States, 94574
      • Saint Helena Hospital
    • San Francisco, California, United States, 94115
      • UCSF-Mount Zion
    • Santa Clara, California, United States, 95051
      • Kaiser Permanente Medical Center - Santa Clara
    • Stanford, California, United States, 94305
      • Stanford University Hospitals and Clinics
    • Vacaville, California, United States, 95687
      • Sutter Cancer Centers Radiation Oncology Services-Vacaville
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Cancer Center - Anschutz Cancer Pavilion
    • Aurora, Colorado, United States, 80012
      • Rocky Mountain Cancer Centers-Aurora
    • Colorado Springs, Colorado, United States, 80907
      • Penrose-Saint Francis Healthcare
    • Denver, Colorado, United States, 80210
      • Porter Adventist Hospital
    • Englewood, Colorado, United States, 80113
      • Swedish Medical Center
    • Littleton, Colorado, United States, 80120
      • Rocky Mountain Cancer Centers-Littleton
  • Connecticut
    • Bridgeport, Connecticut, United States, 06606
      • Saint Vincent's Medical Center
    • New Haven, Connecticut, United States, 06520
      • Yale University
    • Norwich, Connecticut, United States, 06360
      • William Backus Hospital
  • Delaware
    • Newark, Delaware, United States, 19718
      • Christiana Care Health System-Christiana Hospital
  • Florida
    • Deerfield Beach, Florida, United States, 33442
      • University of Miami Sylvester Comprehensive Cancer Center at Deerfield Beach
    • Jacksonville, Florida, United States, 32224-9980
      • Mayo Clinic in Florida
    • Miami, Florida, United States, 33136
      • University of Miami Miller School of Medicine-Sylvester Cancer Center
    • Miami, Florida, United States, 33176
      • Baptist Hospital of Miami
    • Orlando, Florida, United States, 32803
      • Florida Hospital
    • Orlando, Florida, United States, 32806
      • UF Cancer Center at Orlando Health
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University/Winship Cancer Institute
    • Decatur, Georgia, United States, 30033
      • Atlanta VA Medical Center
    • Gainesville, Georgia, United States, 30501
      • Northeast Georgia Medical Center
    • Savannah, Georgia, United States, 31403
      • Memorial Health University Medical Center
    • Savannah, Georgia, United States, 31405
      • Saint Joseph's-Candler Health System
  • Hawaii
    • Honolulu, Hawaii, United States, 96813
      • Queen's Medical Center
    • Honolulu, Hawaii, United States, 96817
      • The Cancer Center of Hawaii-Liliha
    • Honolulu, Hawaii, United States, 96813
      • University of Hawaii
  • Idaho
    • Boise, Idaho, United States, 83706
      • Saint Alphonsus Regional Medical Center
  • Illinois
    • Chicago, Illinois, United States, 60612
      • University of Illinois
    • Chicago, Illinois, United States, 60612-3785
      • John H Stroger Jr Hospital of Cook County
    • Evanston, Illinois, United States, 60201
      • NorthShore University HealthSystem-Evanston Hospital
    • Harvey, Illinois, United States, 60426
      • Ingalls Memorial Hospital
    • Hines, Illinois, United States, 60141
      • Hines Veterans Administration Hospital
    • Maywood, Illinois, United States, 60153
      • Loyola University Medical Center
    • Springfield, Illinois, United States, 62781-0001
      • Memorial Medical Center
    • Springfield, Illinois, United States, 62702
      • Saint John's Hospital
    • Urbana, Illinois, United States, 61801
      • Carle Cancer Center
  • Indiana
    • Fort Wayne, Indiana, United States, 46805
      • Parkview Hospital Randallia
    • Fort Wayne, Indiana, United States, 46804
      • Radiation Oncology Associates PC
    • Indianapolis, Indiana, United States, 46202
      • IU Health Methodist Hospital
    • Indianapolis, Indiana, United States, 46256
      • Community Regional Cancer Care-North
    • Indianapolis, Indiana, United States, 46219
      • Community Regional Cancer Care-East Radiation Oncology
    • Muncie, Indiana, United States, 47303
      • IU Health Ball Memorial Hospital
  • Iowa
    • Ames, Iowa, United States, 50010
      • McFarland Clinic PC-William R Bliss Cancer Center
    • Des Moines, Iowa, United States, 50309
      • Iowa Methodist Medical Center
    • Des Moines, Iowa, United States, 50314
      • Mercy Medical Center - Des Moines
    • Iowa City, Iowa, United States, 52242
      • University of Iowa Hospitals and Clinics
    • Sioux City, Iowa, United States, 51101
      • Siouxland Hematology Oncology Associates
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • University of Kansas Medical Center
  • Kentucky
    • Lexington, Kentucky, United States, 40536
      • University of Kentucky
    • Louisville, Kentucky, United States, 40202
      • The James Graham Brown Cancer Center at University of Louisville
  • Louisiana
    • Baton Rouge, Louisiana, United States, 70809
      • Mary Bird Perkins Cancer Center
    • New Orleans, Louisiana, United States, 70112
      • Tulane University Health Sciences Center
    • New Orleans, Louisiana, United States, 70115
      • Touro Infirmary
  • Maine
    • Lewiston, Maine, United States, 04240
      • Central Maine Medical Center
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • University of Maryland/Greenebaum Cancer Center
    • Salisbury, Maryland, United States, 21801
      • Peninsula Regional Medical Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02111
      • Tufts Medical Center
    • Boston, Massachusetts, United States, 02118
      • Boston Medical Center
    • Burlington, Massachusetts, United States, 01805
      • Lahey Hospital and Medical Center
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan
    • Ann Arbor, Michigan, United States, 48106-0995
      • Saint Joseph Mercy Hospital
    • Dearborn, Michigan, United States, 48124
      • Oakwood Hospital
    • Detroit, Michigan, United States, 48202
      • Henry Ford Hospital
    • Detroit, Michigan, United States, 48236
      • Saint John Hospital and Medical Center
    • Detroit, Michigan, United States, 48201
      • Wayne State University/Karmanos Cancer Institute
    • Kalamazoo, Michigan, United States, 49007
      • West Michigan Cancer Center
    • Saginaw, Michigan, United States, 48601
      • Saint Mary's of Michigan
    • Warren, Michigan, United States, 48093
      • Saint John Macomb-Oakland Hospital
  • Minnesota
    • Coon Rapids, Minnesota, United States, 55433
      • Mercy Hospital
    • Duluth, Minnesota, United States, 55805
      • Saint Luke's Hospital of Duluth
    • Fridley, Minnesota, United States, 55432
      • Unity Hospital
    • Maplewood, Minnesota, United States, 55109
      • Minnesota Oncology Hematology PA-Maplewood
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
    • Saint Paul, Minnesota, United States, 55101
      • Regions Hospital
  • Mississippi
    • Jackson, Mississippi, United States, 39216
      • University of Mississippi Medical Center
    • Pascagoula, Mississippi, United States, 39581
      • Singing River Hospital
  • Missouri
    • Cape Girardeau, Missouri, United States, 63703
      • Cape Radiation Oncology
    • Columbia, Missouri, United States, 65212
      • University of Missouri - Ellis Fischel
    • Kansas City, Missouri, United States, 64154
      • Kansas City Cancer Centers - North
    • Lee's Summit, Missouri, United States, 64064
      • Kansas City Cancer Center-Lee's Summit
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine
    • Saint Louis, Missouri, United States, 63110
      • Saint Louis University Hospital
    • Saint Louis, Missouri, United States, 63131
      • Missouri Baptist Medical Center
    • Saint Louis, Missouri, United States, 63129
      • Siteman Cancer Center-South County
    • Saint Louis, Missouri, United States, 63141
      • Barnes-Jewish West County Hospital
    • Saint Louis, Missouri, United States, 63141
      • Saint John's Mercy Medical Center
    • Saint Peters, Missouri, United States, 63376
      • Siteman Cancer Center - Saint Peters
    • Springfield, Missouri, United States, 65807
      • CoxHealth South Hospital
    • Springfield, Missouri, United States, 65804
      • Mercy Hospital Springfield
  • Nebraska
    • Lincoln, Nebraska, United States, 68510
      • Saint Elizabeth Regional Medical Center
    • Omaha, Nebraska, United States, 68114
      • Nebraska Methodist Hospital
    • Omaha, Nebraska, United States, 68198
      • The Nebraska Medical Center
  • Nevada
    • Reno, Nevada, United States, 89502
      • Renown Regional Medical Center
  • New Hampshire
    • Exeter, New Hampshire, United States, 03833
      • Exeter Hospital
    • Lebanon, New Hampshire, United States, 03756
      • Dartmouth Hitchcock Medical Center
  • New Jersey
    • Basking Ridge, New Jersey, United States, 07920
      • Memorial Sloan Kettering Cancer Center at Basking Ridge
    • Camden, New Jersey, United States, 08103
      • Cooper Hospital University Medical Center
    • Mount Holly, New Jersey, United States, 08060
      • Fox Chase Cancer Center at Virtua Memorial Hospital of Burlington County
    • New Brunswick, New Jersey, United States, 08901
      • Saint Peter's University Hospital
    • Newark, New Jersey, United States, 07103
      • UMDNJ - New Jersey Medical School
    • Sparta, New Jersey, United States, 07871
      • Sparta Cancer Treatment Center
    • Voorhees, New Jersey, United States, 08043
      • MD Anderson Cancer Center at Cooper-Voorhees
  • New Mexico
    • Albuquerque, New Mexico, United States, 87106
      • University of New Mexico
  • New York
    • Albany, New York, United States, 12206
      • New York Oncology Hematology PC - Albany
    • Brooklyn, New York, United States, 11219
      • Maimonides Medical Center
    • Canandaigua, New York, United States, 14424
      • Sands Cancer Center
    • Commack, New York, United States, 11725
      • Memorial Sloan Kettering Cancer Center Commack
    • New York, New York, United States, 10065
      • Memorial Sloan-Kettering Cancer Center
    • New York, New York, United States, 10003
      • Beth Israel Medical Center
    • Rochester, New York, United States, 14642
      • University of Rochester
    • Rochester, New York, United States, 14620
      • Highland Hospital
    • Rochester, New York, United States, 14626
      • University Radiation Oncology
    • Rockville Centre, New York, United States, 11570
      • Memorial Sloan-Kettering Cancer Center Rockville Centre
    • Sleepy Hollow, New York, United States, 10591
      • Memorial Sloan-Kettering Cancer Center at Sleepy Hallow
  • North Carolina
    • Asheville, North Carolina, United States, 28801
      • Mission Hospital-Memorial Campus
    • Chapel Hill, North Carolina, United States, 27599
      • University of North Carolina
    • Goldsboro, North Carolina, United States, 27534
      • Wayne Radiation Oncology
    • Kinston, North Carolina, United States, 28501
      • Kinston Medical Specialists PA
    • Raleigh, North Carolina, United States, 27607
      • Cancer Centers of North Carolina
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest University Health Sciences
  • North Dakota
    • Fargo, North Dakota, United States, 58122
      • Roger Maris Cancer Center
  • Ohio
    • Akron, Ohio, United States, 44304
      • Summa Akron City Hospital/Cooper Cancer Center
    • Akron, Ohio, United States, 44307
      • Akron General Medical Center
    • Barberton, Ohio, United States, 44203
      • Summa Barberton Hospital
    • Canton, Ohio, United States, 44708
      • Mercy Medical Center
    • Chardon, Ohio, United States, 44024
      • Geaugra Hospital
    • Cincinnati, Ohio, United States, 45267
      • University of Cincinnati
    • Cleveland, Ohio, United States, 44106
      • Case Western Reserve University
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Foundation
    • Cleveland, Ohio, United States, 44111
      • Cleveland Clinic Cancer Center/Fairview Hospital
    • Columbus, Ohio, United States, 43210
      • Ohio State University Medical Center
    • Elyria, Ohio, United States, 44035
      • Mercy Cancer Center-Elyria
    • Independence, Ohio, United States, 44131
      • Cleveland Clinic Cancer Center Independence
    • Mayfield Heights, Ohio, United States, 44124
      • Hillcrest Hospital Cancer Center
    • Medina, Ohio, United States, 44256
      • Summa Health Center at Lake Medina
    • Mentor, Ohio, United States, 44060
      • Lake University Ireland Cancer Center
    • Middleburg Heights, Ohio, United States, 44130
      • Southwest General Health Center Ireland Cancer Center
    • Orange Village, Ohio, United States, 44122
      • UHHS-Chagrin Highlands Medical Center
    • Oregon, Ohio, United States, 43616
      • Saint Charles Hospital
    • Ravenna, Ohio, United States, 44266
      • Robinson Radiation Oncology
    • Sandusky, Ohio, United States, 44870
      • North Coast Cancer Care
    • Strongsville, Ohio, United States, 44136
      • Cleveland Clinic Cancer Center-Strongsville
    • Sylvania, Ohio, United States, 43560
      • Flower Hospital
    • West Chester, Ohio, United States, 45069
      • University Pointe
    • Westlake, Ohio, United States, 44145
      • UHHS-Westlake Medical Center
    • Wooster, Ohio, United States, 44691
      • Cleveland Clinic Wooster Specialty Center
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • University of Oklahoma Health Sciences Center
  • Oregon
    • Clackamas, Oregon, United States, 97015
      • Clackamas Radiation Oncology Center
    • Eugene, Oregon, United States, 97401
      • Willamette Valley Cancer Center
    • Portland, Oregon, United States, 97239
      • Oregon Health and Science University
    • Portland, Oregon, United States, 97213
      • Providence Portland Medical Center
    • Portland, Oregon, United States, 97225
      • Providence Saint Vincent Medical Center
    • Portland, Oregon, United States, 97213
      • Western Oncology Research Consortium
    • Portland, Oregon, United States, 97239
      • Portland Veterans Administration Medical Center
    • Salem, Oregon, United States, 97301
      • Salem Hospital
  • Pennsylvania
    • Allentown, Pennsylvania, United States, 18105
      • LeHigh Valley Hospital
    • Danville, Pennsylvania, United States, 17822-2001
      • Geisinger Medical Center
    • Dunmore, Pennsylvania, United States, 18512
      • Northeast Radiation Oncology Center
    • East Stroudsburg, Pennsylvania, United States, 18301
      • Pocono Medical Center
    • Gettysburg, Pennsylvania, United States, 17325
      • Adams Cancer Center
    • Hanover, Pennsylvania, United States, 17331
      • Cherry Tree Cancer Center
    • Langhorne, Pennsylvania, United States, 19047
      • Saint Mary Medical and Regional Cancer Center
    • Philadelphia, Pennsylvania, United States, 19111
      • Fox Chase Cancer Center
    • Philadelphia, Pennsylvania, United States, 19141
      • Albert Einstein Medical Center
    • Philadelphia, Pennsylvania, United States, 19107
      • Thomas Jefferson University Hospital
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania/Abramson Cancer Center
    • West Reading, Pennsylvania, United States, 19611
      • Reading Hospital
    • York, Pennsylvania, United States, 17405
      • WellSpan Health-York Hospital
  • South Carolina
    • Anderson, South Carolina, United States, 29621
      • AnMed Health Cancer Center
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina
    • Greenville, South Carolina, United States, 29605
      • Greenville Health System Cancer Institute-Faris
    • Greenville, South Carolina, United States, 29615
      • Greenville Health System Cancer Institute/Greenville CCOP
    • Greer, South Carolina, United States, 29651
      • Gibbs Cancer Center-Pelham
    • Spartanburg, South Carolina, United States, 29307
      • Greenville Health System Cancer Institute-Spartanburg
    • Spartanburg, South Carolina, United States, 29303
      • Spartanburg Regional Medical Center
  • South Dakota
    • Rapid City, South Dakota, United States, 57701
      • Rapid City Regional Hospital
    • Sioux Falls, South Dakota, United States, 57104
      • Sanford Cancer Center-Oncology Clinic
  • Tennessee
    • Kingsport, Tennessee, United States, 37660
      • Wellmont Holston Valley Hospital and Medical Center
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt-Ingram Cancer Center
  • Texas
    • Austin, Texas, United States, 78705
      • Texas Oncology-Austin Midtown
    • Austin, Texas, United States, 78731
      • Texas Oncology - Central Austin Cancer Center
    • Austin, Texas, United States, 78745
      • Texas Oncology - South Austin Cancer Center
    • Bedford, Texas, United States, 76022
      • Texas Oncology PA - Bedford
    • Dallas, Texas, United States, 75390
      • University of Texas Southwestern Medical Center
    • Denton, Texas, United States, 76210
      • Texas Oncology-Denton South
    • Fort Worth, Texas, United States, 76104
      • The Klabzuba Cancer Center
    • Houston, Texas, United States, 77030
      • M D Anderson Cancer Center
    • Houston, Texas, United States, 77030
      • Ben Taub General Hospital
    • Houston, Texas, United States, 77024
      • Memorial Hermann Memorial City Medical Center
    • Round Rock, Texas, United States, 78665
      • Texas Oncology-Seton Williamson
    • Round Rock, Texas, United States, 78681
      • Texas Oncology - Round Rock Cancer Center
    • San Antonio, Texas, United States, 78229
      • University of Texas Health Science Center at San Antonio
    • San Antonio, Texas, United States, 78217
      • Cancer Care Centers of South Texas- Northeast
    • Sherman, Texas, United States, 75090
      • Texas Cancer Center-Sherman
    • Sugar Land, Texas, United States, 77479
      • Texas Oncology Cancer Center Sugar Land
    • Wichita Falls, Texas, United States, 76310
      • Texas Oncology-Wichita Falls Texoma Cancer Center
  • Utah
    • Murray, Utah, United States, 84157
      • Intermountain Medical Center
    • Saint George, Utah, United States, 84770
      • Dixie Medical Center Regional Cancer Center
    • Salt Lake City, Utah, United States, 84112
      • Huntsman Cancer Institute/University of Utah
    • Salt Lake City, Utah, United States, 84106
      • Utah Cancer Specialists-Salt Lake City
    • Salt Lake City, Utah, United States, 84143
      • LDS Hospital
  • Virginia
    • Charlottesville, Virginia, United States, 22908
      • University of Virginia
    • Hampton, Virginia, United States, 23666
      • Sentara Cancer Institute at Sentara CarePlex Hospital
    • Norfolk, Virginia, United States, 23507
      • Sentara Hospitals
    • Richmond, Virginia, United States, 23298
      • Virginia Commonwealth University
    • Richmond, Virginia, United States, 23249
      • Hunter Holmes McGuire Veterans Administration Medical Center
    • Virginia Beach, Virginia, United States, 23454
      • Sentara Virginia Beach General Hospital
  • Washington
    • Bremerton, Washington, United States, 98310
      • Harrison Medical Center
    • Kennewick, Washington, United States, 99336
      • Tri-Cities Cancer Center
    • Mount Vernon, Washington, United States, 98274
      • Skagit Valley Hospital
    • Seattle, Washington, United States, 98195
      • University of Washington Medical Center
    • Spokane, Washington, United States, 99202
      • Cancer Care Northwest - Spokane South
    • Spokane, Washington, United States, 99218
      • Cancer Care Northwest-North Spokane
    • Tacoma, Washington, United States, 98405
      • Northwest CCOP
    • Vancouver, Washington, United States, 98664
      • PeaceHealth Southwest Medical Center
    • Vancouver, Washington, United States, 98684
      • Compass Oncology Vancouver
    • Wenatchee, Washington, United States, 98801
      • Wenatchee Valley Medical Center
  • West Virginia
    • Morgantown, West Virginia, United States, 26506
      • West Virginia University Healthcare
    • Wheeling, West Virginia, United States, 26003
      • Wheeling Hospital
  • Wisconsin
    • Antigo, Wisconsin, United States, 54409
      • Langlade Hospital and Cancer Center
    • Appleton, Wisconsin, United States, 54911-3496
      • Fox Valley Hematology and Oncology
    • Green Bay, Wisconsin, United States, 54301
      • Saint Vincent Hospital
    • La Crosse, Wisconsin, United States, 54601
      • Gundersen Lutheran
    • Madison, Wisconsin, United States, 53792
      • University of Wisconsin Hospital and Clinics
    • Marinette, Wisconsin, United States, 54143
      • Bay Area Medical Center
    • Milwaukee, Wisconsin, United States, 53226
      • Froedtert and The Medical College of Wisconsin
    • Milwaukee, Wisconsin, United States, 53295
      • Clement J. Zablocki VA Medical Center
    • Sturgeon Bay, Wisconsin, United States, 54235-1495
      • Door County Cancer Center
    • Wausau, Wisconsin, United States, 54401
      • Aspirus Regional Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

DISEASE CHARACTERISTICS:

• Histologically confirmed squamous cell carcinoma (including variants, such as verrucous carcinoma, spindle cell carcinoma, or carcinoma not otherwise specified) of the head and neck, including the following subtypes:

  • Oral cavity
  • Oropharynx
  • Larynx

• Clinical stage T1, N1-2, M0 OR T2-4a, N0-2, M0 disease based on the following diagnostic workup within the past 8 weeks:

  • General history and physical examination by a Radiation Oncologist and/or Medical Oncologist
  • Chest x-ray or chest CT scan (with or without contrast) or chest CT/PET scan (with or without contrast)

• Must have undergone gross total resection of the primary tumor with curative intent within the past 7 weeks with surgical pathology demonstrating ≥ 1 of the following criteria for "intermediate" risk of recurrence:

  • 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
• No 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

PATIENT CHARACTERISTICS:

• Zubrod performance status 0-1
• Absolute granulocyte count ≥ 1,500/mm³
• Platelet count ≥ 100,000/mm³
• Hemoglobin ≥ 8.0 g/dL (transfusion or other intervention allowed)
• Total bilirubin < 2 times upper limit of normal (ULN)
• Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) < 3 times ULN
• Serum creatinine < 2 times ULN OR creatinine clearance ≥ 50 mL/min
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No other invasive malignancy within the past 3 years, except for nonmelanomatous skin cancer or previously treated carcinoma in situ of the breast, oral cavity, or cervix
• No simultaneous primary or bilateral tumors

• No severe, active co-morbidity, including any of the following:

  • Unstable angina and/or congestive heart failure requiring hospitalization within the past 6 months
  • Transmural myocardial infarction within the past 6 months
  • Acute bacterial or fungal infection requiring IV antibiotics at the time of study registration
  • Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy
  • Idiopathic pulmonary fibrosis or other severe interstitial lung disease that requires oxygen therapy or is thought to have required oxygen therapy within the past year
  • Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects
  • AIDS based on current Centers for Disease Control (CDC) definition

  • Grade 3-4 electrolyte abnormalities according to CTCAE, v. 4, including any of the following:

    • Serum calcium (ionized or adjusted for albumin) < 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 < 3.0 mmol/L or > 6 mmol/L*
    • Sodium < 130 mmol/L or > 155 mmol/L* NOTE: *Despite intervention to normalize levels.
• No prior allergic reaction to cetuximab

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics

• No prior systemic chemotherapy or anti-epidermal growth factor (EGF) therapy for this cancer

  • Prior chemotherapy or anti-EGF therapy for a different cancer allowed
• No prior radiotherapy to the region of the study cancer that would result in overlap of radiotherapy fields
• No concurrent amifostine as a radioprotector
• No concurrent granulocyte colony-stimulating factor or erythropoietin

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Arm I: Intensity-Modulated Radiotherapy; Patients undergo intensity-modulated radiotherapy (IMRT) once daily 5 days a week for 6 weeks in the absence of disease progression or unacceptable toxicity.	Radiation: intensity-modulated radiation therapy; Patients undergo radiotherapy.
Experimental: Arm II: IMRT plus cetuximab; 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.	Biological: cetuximab; Given IV; Radiation: intensity-modulated radiation therapy; Patients undergo radiotherapy.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Overall survival	From randomization to date of death or last follow-up. Analysis occurs after 372 events have been reported.

Secondary Outcome Measures

Outcome Measure	Time Frame
Adverse events (dysphagia, xerostomia, and skin toxicity) according to CTCAE, v. 4 and their relationships with patient-reported outcomes at 3, 12, and 24 months	From start of treatment to 2 years after end of treatment.
Other acute adverse events (≤ 90 days from start of radiotherapy [RT]) according to CTCAE, v. 4	From start of treatment to 90 days.
Other late adverse events (> 90 days from start of RT) according to CTCAE, v. 4	From 90 days after start of treatment to last follow-up.
Disease-free survival	From randomization to date of failure (local, regional or distant progression or death) or last follow-up. Analysis occurs at the same time as the primary outcome.
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.
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.
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.
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.
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.

Collaborators and Investigators

• Sponsor: Radiation Therapy Oncology Group
• Collaborators: National Cancer Institute (NCI); NRG Oncology
• Investigators: Study Chair: Mitchell Machtay, MD, University Hospitals Seidman Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2009
• Primary Completion (Actual): September 5, 2023
• Study Completion (Estimated): August 1, 2029

Study Registration Dates

• First Submitted: August 8, 2009
• First Submitted That Met QC Criteria: August 8, 2009
• First Posted (Estimated): August 11, 2009

Study Record Updates

• Last Update Posted (Actual): March 15, 2024
• Last Update Submitted That Met QC Criteria: March 12, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: stage III squamous cell carcinoma of the lip and oral cavity; stage III verrucous carcinoma of the oral cavity; stage IV squamous cell carcinoma of the lip and oral cavity; stage IV verrucous carcinoma of the oral cavity; stage III squamous cell carcinoma of the oropharynx; stage IV squamous cell carcinoma of the oropharynx; stage III squamous cell carcinoma of the larynx; stage III verrucous carcinoma of the larynx; stage IV squamous cell carcinoma of the larynx; stage IV verrucous carcinoma of the larynx; tongue cancer
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Site; Head and Neck Neoplasms; Antineoplastic Agents; Antineoplastic Agents, Immunological; Cetuximab
• Other Study ID Numbers: RTOG 0920; CDR0000651536; NCI-2011-00878 (Registry Identifier: CTRP (Clinical Trials Reporting Program)