Adjuvant Cetuximab and Chemoradiotherapy Using Either Cisplatin or Docetaxel in Treating Patients With Resected Stage III or Stage IV Squamous Cell Carcinoma or Lymphoepithelioma of the Head and Neck

A Phase II Randomized Trial Of Surgery Followed By Chemoradiotherapy Plus Cetuximab For Advanced Squamous Cell Carcinoma Of The Head and Neck

RATIONALE: Monoclonal antibodies such as cetuximab can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. Drugs used in chemotherapy, such as cisplatin and docetaxel, work in different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells. Cisplatin and docetaxel may make the tumor cells more sensitive to radiation therapy. Combining a monoclonal antibody with chemoradiotherapy and giving them after surgery may kill any remaining tumor cells.

PURPOSE: This randomized phase II trial is studying adjuvant cetuximab given together with chemoradiotherapy using cisplatin to see how well it works compared to adjuvant cetuximab given together with chemoradiotherapy using docetaxel in treating patients with resected stage III or stage IV squamous cell carcinoma (cancer) or lymphoepithelioma of the head and neck.

Study Overview

• Status: Completed
• Conditions: Head and Neck Cancer
• Intervention / Treatment: Biological: cetuximab; Drug: cisplatin; Radiation: radiation therapy; Drug: docetaxel

Detailed Description

OBJECTIVES:

Primary

• Compare disease-free survival of patients with resected stage III or IV squamous cell carcinoma or lymphoepithelioma of the head and neck treated with adjuvant cetuximab in combination with chemoradiotherapy comprising docetaxel vs cisplatin.

Secondary

• Compare the safety and efficacy of these regimens in these patients.
• Compare locoregional control and overall survival rates in patients treated with these regimens.
• Correlate epidermal growth factor receptor (total and phosphorylated), pMAPK, pAKT, Stat-3, Ki-67, cyclo-oxygenase-2, and cyclin B1 expression with outcome in patients treated with these regimens.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to Zubrod performance status (0 vs 1), risk category (positive margins vs high risk [i.e., ≥ 2 positive nodes or extracapsular nodal extension]) and use of intensity-modulated radiotherapy (no vs yes). Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive cetuximab IV over 2 hours on day 1 (week 1). Patients then receive cetuximab IV over 1 hour and cisplatin IV over 1 hour before radiotherapy on days 8, 15, 22, 29, 36, and 43 (weeks 2-7). Patients undergo radiotherapy once daily, 5 days a week, beginning on day 8 for a total of 6 weeks (weeks 2-7).
• Arm II: Patients receive cetuximab and undergo radiotherapy as in arm I. Patients also receive docetaxel IV over 30 minutes before radiotherapy on days 8, 15, 22, 29, 36, and 43 (weeks 2-7).

Treatment in both arms continues in the absence of disease progression or unacceptable toxicity.

Patients are followed every 3 months for 2 years and then every 6 months for 4 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 230 patients (115 per treatment arm) will be accrued for this study within approximately 29 months.

• Study Type: Interventional
• Enrollment (Actual): 238
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • University of Alabama at Birmingham Comprehensive Cancer Center
    • Mobile, Alabama, United States, 36652-2144
      • Mobile Infirmary Medical Center
  • Arizona
    • Phoenix, Arizona, United States, 85013
      • Arizona Oncology Services Foundation
    • Scottsdale, Arizona, United States, 85259-5499
      • Mayo Clinic Scottsdale
    • Scottsdale, Arizona, United States, 85260
      • Virginia G. Piper Cancer Center at Scottsdale Healthcare - Shea
    • Scottsdale, Arizona, United States, 85251
      • Virginia G. Piper Cancer Center at Scottsdale Healthcare - Osborn
  • California
    • Auburn, California, United States, 95603
      • Auburn Radiation Oncology
    • Burbank, California, United States, 91505
      • Providence Saint Joseph Medical Center - Burbank
    • Cameron Park, California, United States, 95682
      • Radiation Oncology Centers - Cameron Park
    • Carmichael, California, United States, 95608
      • Mercy Cancer Center at Mercy San Juan Medical Center
    • Loma Linda, California, United States, 92354
      • Loma Linda University Cancer Institute at Loma Linda University Medical Center
    • Mission Hills, California, United States, 91346-9600
      • Providence Holy Cross Cancer Center
    • Oakland, California, United States, 94609
      • CCOP - Bay Area Tumor Institute
    • Roseville, California, United States, 95661
      • Radiation Oncology Center - Roseville
    • Sacramento, California, United States, 95815
      • Radiological Associates of Sacramento Medical Group, Incorporated
    • Sacramento, California, United States, 95819
      • Mercy General Hospital
    • Sacramento, California, United States, 95817
      • University of California Davis Cancer Center
    • Torrance, California, United States, 90509
      • Torrance Memorial Medical Center
    • Vacaville, California, United States, 95687
      • Solano Radiation Oncology Center
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Cancer Center at University of Colorado Health Sciences Center
  • Connecticut
    • New Haven, Connecticut, United States, 06511
      • Hospital of Saint Raphael
  • Delaware
    • Newark, Delaware, United States, 19713
      • CCOP - Christiana Care Health Services
  • Florida
    • Boca Raton, Florida, United States, 33486
      • Lynn Regional Cancer Center at Boca Raton Community Hospital - Main Center
    • Fort Lauderdale, Florida, United States, 33308
      • Michael & Dianne Bienes Comprehensive Cancer Center at Holy Cross Hospital
    • Jacksonville, Florida, United States, 32224
      • Mayo Clinic - Jacksonville
    • Jacksonville, Florida, United States, 32207
      • Baptist Cancer Institute - Jacksonville
    • Jupiter, Florida, United States, 33458
      • Ella Milbank Foshay Cancer Center at Jupiter Medical Center
    • Miami, Florida, United States, 33136
      • University of Miami Sylvester Comprehensive Cancer Center
    • Miami Beach, Florida, United States, 33140
      • CCOP - Mount Sinai Medical Center
    • Orlando, Florida, United States, 32806
      • M.D. Anderson Cancer Center Orlando
    • Tallahassee, Florida, United States, 32308
      • Tallahassee Memorial Hospital
    • Tampa, Florida, United States, 33612-9497
      • H. Lee Moffitt Cancer Center and Research Institute at University of South Florida
  • Georgia
    • Columbus, Georgia, United States, 31904
      • John B. Amos Cancer Center
    • Gainesville, Georgia, United States, 30501
      • Northeast Georgia Medical Center
    • Savannah, Georgia, United States, 31403-3089
      • Curtis & Elizabeth Anderson Cancer Institute at Memorial Health University Medical Center
  • Illinois
    • Alton, Illinois, United States, 62002
      • Saint Anthony's Hospital at Saint Anthony's Health Center
    • Harvey, Illinois, United States, 60426
      • Ingalls Cancer Care Center at Ingalls Memorial Hospital
    • Maywood, Illinois, United States, 60153
      • Cardinal Bernardin Cancer Center at Loyola University Medical Center
    • Mount Vernon, Illinois, United States, 62864
      • Good Samaritan Regional Health Center
    • Springfield, Illinois, United States, 62702
      • Cancer Institute at St. John's Hospital
  • Indiana
    • Elkhart, Indiana, United States, 46515
      • Elkhart General Hospital
    • La Porte, Indiana, United States, 46350
      • Center for Cancer Therapy at LaPorte Hospital and Health Services
    • South Bend, Indiana, United States, 46601
      • Memorial Hospital of South Bend
    • South Bend, Indiana, United States, 46601
      • CCOP - Northern Indiana CR Consortium
  • Iowa
    • Dubuque, Iowa, United States, 52001
      • Wendt Regional Cancer Center at Finley Hospital
  • Kentucky
    • Lexington, Kentucky, United States, 40536-0293
      • Markey Cancer Center at University of Kentucky Chandler Medical Center
    • Lexington, Kentucky, United States, 40504
      • John D. Cronin Cancer Center
  • Louisiana
    • Alexandria, Louisiana, United States, 71315-3198
      • Tulane Cancer Center
  • Maryland
    • Baltimore, Maryland, United States, 21231-2410
      • Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital Cancer Center
    • Boston, Massachusetts, United States, 02118
      • Cancer Research Center at Boston Medical Center
    • Boston, Massachusetts, United States, 02115
      • Dana-Farber/Brigham and Women's Cancer Center
    • Fall River, Massachusetts, United States, 02721
      • Hudner Oncology Center at Saint Anne's Hospital - Fall River
  • Michigan
    • Ann Arbor, Michigan, United States, 48106-0995
      • St. Joseph Mercy Cancer Center at St. Joseph Mercy Hospital
    • Detroit, Michigan, United States, 48202
      • Josephine Ford Cancer Center at Henry Ford Hospital
    • Flint, Michigan, United States, 48503
      • Hurley Medical Center
    • Flint, Michigan, United States, 48503
      • Genesys Hurley Cancer Institute
    • Grand Rapids, Michigan, United States, 49503
      • CCOP - Grand Rapids
    • Grand Rapids, Michigan, United States, 49503
      • Lacks Cancer Center at Saint Mary's Health Care
    • Kalamazoo, Michigan, United States, 49007
      • Bronson Methodist Hospital
    • Kalamazoo, Michigan, United States, 49001
      • Borgess Medical Center
    • Kalamazoo, Michigan, United States, 49007-3731
      • West Michigan Cancer Center
    • Marquette, Michigan, United States, 49855
      • Upper Michigan Cancer Center at Marquette General Hospital
    • Saint Joseph, Michigan, United States, 49085
      • Lakeland Cancer Care Center at Lakeland Hospital - St. Joseph
  • Minnesota
    • Burnsville, Minnesota, United States, 55337
      • Fairview Ridges Hospital
    • Coon Rapids, Minnesota, United States, 55433
      • Mercy and Unity Cancer Center at Mercy Hospital
    • Edina, Minnesota, United States, 55435
      • Fairview Southdale Hospital
    • Fridley, Minnesota, United States, 55432
      • Mercy and Unity Cancer Center at Unity Hospital
    • Minneapolis, Minnesota, United States, 55455
      • University of Minnesota Medical Center & Children's Hospital - Fairview
    • Minneapolis, Minnesota, United States, 55407
      • Virginia Piper Cancer Institute at Abbott-Northwestern Hospital
    • Robbinsdale, Minnesota, United States, 55422-2900
      • Hubert H. Humphrey Cancer Center at North Memorial Medical Center
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic Cancer Center
    • Saint Cloud, Minnesota, United States, 56303
      • CentraCare Clinic - River Campus
    • Saint Cloud, Minnesota, United States, 56303
      • Coborn Cancer Center
    • Saint Louis Park, Minnesota, United States, 55416
      • CCOP - Metro-Minnesota
    • Saint Louis Park, Minnesota, United States, 55416
      • Park Nicollet Health Services
    • Saint Paul, Minnesota, United States, 55102
      • United Hospital
    • Waconia, Minnesota, United States, 55387
      • Ridgeview Medical Center
  • Mississippi
    • Pascagoula, Mississippi, United States, 39581
      • Regional Cancer Center at Singing River Hospital
  • Missouri
    • Cape Girardeau, Missouri, United States, 63701
      • Southeast Missouri Regional Cancer Center at Southeast Missouri Hospital
    • Cape Girardeau, Missouri, United States, 63701
      • Saint Francis Medical Center
    • Kansas City, Missouri, United States, 64131
      • CCOP - Kansas City
    • Saint Louis, Missouri, United States, 63141
      • CCOP - St. Louis-Cape Girardeau
    • Saint Louis, Missouri, United States, 63141
      • David C. Pratt Cancer Center at St. John's Mercy
    • Saint Louis, Missouri, United States, 63110
      • Siteman Cancer Center at Barnes-Jewish Hospital
    • Springfield, Missouri, United States, 65804
      • St. John's Regional Health Center
    • Springfield, Missouri, United States, 65807
      • Hulston Cancer Center at Cox Medical Center South
  • Nebraska
    • Kearney, Nebraska, United States, 68848-1990
      • Good Samaritan Cancer Center at Good Samaritan Hospital
    • Omaha, Nebraska, United States, 68114
      • Methodist Cancer Center at Methodist Hospital - Omaha
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03756-0002
      • Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center
  • New Jersey
    • Camden, New Jersey, United States, 08103
      • Cancer Institute of New Jersey at Cooper University Hospital - Camden
    • East Orange, New Jersey, United States, 07018-1095
      • Veterans Affairs Medical Center - East Orange
    • Marlton, New Jersey, United States, 08053
      • Fox Chase Virtua Health Cancer Program at Virtua Memorial Hospital Marlton
    • New Brunswick, New Jersey, United States, 08903
      • Saint Peter's University Hospital
    • Toms River, New Jersey, United States, 08755
      • J. Phillip Citta Regional Cancer Center at Community Medical Center
    • Voorhees, New Jersey, United States, 08043
      • Fox Chase Virtua Health Cancer Program at Virtua West Jersey
  • New York
    • Brooklyn, New York, United States, 11201
      • Long Island College Hospital
    • Buffalo, New York, United States, 14263-0001
      • Roswell Park Cancer Institute
    • New York, New York, United States, 10021
      • Memorial Sloan-Kettering Cancer Center
    • Syracuse, New York, United States, 13210
      • SUNY Upstate Medical University Hospital
  • North Carolina
    • Asheville, North Carolina, United States, 28801
      • Mission Hospitals - Memorial Campus
    • Charlotte, North Carolina, United States, 28232-2861
      • Blumenthal Cancer Center at Carolinas Medical Center
    • Goldsboro, North Carolina, United States, 27534
      • Wayne Memorial Hospital, Incorporated
    • Greenville, North Carolina, United States, 27835-6028
      • Leo W. Jenkins Cancer Center at ECU Medical School
    • Statesville, North Carolina, United States, 28677
      • Iredell Memorial Hospital
    • Winston-Salem, North Carolina, United States, 27103
      • Forsyth Regional Cancer Center at Forsyth Medical Center
  • Ohio
    • Akron, Ohio, United States, 44307
      • McDowell Cancer Center at Akron General Medical Center
    • Akron, Ohio, United States, 44309-2090
      • Akron City Hospital
    • Cincinnati, Ohio, United States, 45267
      • Charles M. Barrett Cancer Center at University Hospital
    • Columbus, Ohio, United States, 43210-1240
      • Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University
    • Mayfield Heights, Ohio, United States, 44124
      • Hillcrest Cancer Center at Hillcrest Hospital
  • Oregon
    • Portland, Oregon, United States, 97239-3098
      • Oregon Health & Science University Cancer Institute
  • Pennsylvania
    • Abington, Pennsylvania, United States, 19001
      • Rosenfeld Cancer Center at Abington Memorial Hospital
    • Bryn Mawr, Pennsylvania, United States, 19010
      • Bryn Mawr Hospital
    • East Stroudsburg, Pennsylvania, United States, 18301
      • Dale and Frances Hughes Cancer Center at Pocono Medical Center
    • Hershey, Pennsylvania, United States, 17033-0850
      • Penn State Cancer Institute at Milton S. Hershey Medical Center
    • Paoli, Pennsylvania, United States, 19301-1792
      • Cancer Center of Paoli Memorial Hospital
    • Philadelphia, Pennsylvania, United States, 19111-2497
      • Fox Chase Cancer Center - Philadelphia
    • Philadelphia, Pennsylvania, United States, 19107-5541
      • Kimmel Cancer Center at Thomas Jefferson University - Philadelphia
    • Pittsburgh, Pennsylvania, United States, 15219
      • Mercy Cancer Institute at Mercy Hospital
    • Reading, Pennsylvania, United States, 19612-6052
      • Reading Hospital and Medical Center
    • Sayre, Pennsylvania, United States, 18840
      • Guthrie Cancer Center at Guthrie Clinic Sayre
    • State College, Pennsylvania, United States, 16803
      • Mount Nittany Medical Center
    • Wynnewood, Pennsylvania, United States, 19096
      • CCOP - MainLine Health
    • Wynnewood, Pennsylvania, United States, 19096
      • Lankenau Cancer Center at Lankenau Hospital
    • York, Pennsylvania, United States, 17405
      • York Cancer Center at Apple Hill Medical Center
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Hollings Cancer Center at Medical University of South Carolina
    • Greenville, South Carolina, United States, 29615
      • CCOP - Greenville
    • Greenville, South Carolina, United States, 29601
      • Bon Secours St. Francis Health System
    • Spartanburg, South Carolina, United States, 29303
      • CCOP - Upstate Carolina
    • Spartanburg, South Carolina, United States, 29303
      • Gibbs Regional Cancer Center at Spartanburg Regional Medical Center
  • South Dakota
    • Rapid City, South Dakota, United States, 57701
      • Rapid City Regional Hospital
  • Tennessee
    • Kingsport, Tennessee, United States, 37662
      • Christine LaGuardia Phillips Cancer Center at Wellmont Holston Valley Medical Center
    • Knoxville, Tennessee, United States, 37916
      • Thompson Cancer Survival Center
  • Texas
    • Houston, Texas, United States, 77030-4009
      • M.D. Anderson Cancer Center at University of Texas
    • Temple, Texas, United States, 76508
      • CCOP - Scott and White Hospital
  • Utah
    • Murray, Utah, United States, 84107
      • Cottonwood Hospital Medical Center
    • Ogden, Utah, United States, 84403
      • McKay-Dee Hospital Center
    • Provo, Utah, United States, 84604
      • Utah Valley Regional Medical Center - Provo
    • Saint George, Utah, United States, 84770
      • Dixie Regional Medical Center - East Campus
    • Salt Lake City, Utah, United States, 84112
      • Huntsman Cancer Institute at University of Utah
    • Salt Lake City, Utah, United States, 84106
      • Utah Cancer Specialists at UCS Cancer Center
    • Salt Lake City, Utah, United States, 84143
      • Latter Day Saints Hospital
  • Virginia
    • Danville, Virginia, United States, 24541
      • Danville Regional Medical Center
    • Richmond, Virginia, United States, 23249
      • Veterans Affairs Medical Center - Richmond
    • Richmond, Virginia, United States, 23298-0037
      • Virginia Commonwealth University Massey Cancer Center
  • Washington
    • Bellingham, Washington, United States, 98225
      • St. Joseph Cancer Center
    • Seattle, Washington, United States, 98101
      • CCOP - Virginia Mason Research Center
    • Seattle, Washington, United States, 98195-6043
      • University Cancer Center at University of Washington Medical Center
  • West Virginia
    • Wheeling, West Virginia, United States, 26003
      • Schiffler Cancer Center at Wheeling Hospital
  • Wisconsin
    • Green Bay, Wisconsin, United States, 54307-3508
      • St. Vincent Hospital Regional Cancer Center
    • Green Bay, Wisconsin, United States, 54303
      • Green Bay Oncology, Limited at St. Mary's Hospital
    • Green Bay, Wisconsin, United States, 54303
      • St. Mary's Hospital Medical Center - Green Bay
    • Green Bay, Wisconsin, United States, 54301-3526
      • Green Bay Oncology, Limited at St. Vincent Hospital
    • La Crosse, Wisconsin, United States, 54601
      • Gundersen Lutheran Cancer Center at Gundersen Lutheran Medical Center
    • Madison, Wisconsin, United States, 53792-6164
      • University of Wisconsin Comprehensive Cancer Center
    • Marinette, Wisconsin, United States, 54143
      • Bay Area Cancer Care Center at Bay Area Medical Center
    • Milwaukee, Wisconsin, United States, 53226
      • Medical College of Wisconsin Cancer Center
    • Racine, Wisconsin, United States, 53405
      • All Saints Cancer Center at All Saints Healthcare

Participation Criteria

Eligibility Criteria

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

Description

DISEASE CHARACTERISTICS:

• Histologically confirmed squamous cell carcinoma of the head and neck meeting the following criteria:

  • Site of tumor origin in the oral cavity, oropharynx, larynx, or hypopharynx (excluding lip, nasopharynx, or sinuses)

  • Gross total resection must be completed within 7 weeks of randomization, with pathology demonstrating one or more of the following risk factors:

    • Histologic extracapsular nodal extension
    • Histologic involvement of ≥ 2 regional lymph nodes
    • Invasive cancer seen on microscopic evaluation of the resection margin, with no evidence of gross tumor residual.
    • Tonsillar cancer patients who undergo transoral excision of all gross tumor are eligible provided extracapsular nodal extension or involvement of ≥ 2 regional lymph nodes is histologically confirmed
  • American Joint Committee on Cancer (AJCC) pathological stage III or IV
• No evidence of distant metastases
• No synchronous or concurrent head and neck primary tumors

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• Zubrod 0-1

Life expectancy

• Not specified

Hematopoietic

• Absolute neutrophil count ≥ 2,000/mm^3
• Platelet count ≥ 100,000/mm^3
• Hemoglobin > 8.0 g/dL

Hepatic

• Bilirubin ≤ 1.5 times upper limit of normal (ULN)

• Aspartate aminotransferase (AST) or alanine aminotransferase (ALT), and alkaline phosphatase meeting 1 of the following parameters:

  • Alkaline phosphatase ≤ ULN AND AST or ALT ≤ 5 times ULN
  • Alkaline phosphatase ≤ 2.5 times ULN AND AST or ALT ≤ 1.5 times ULN
  • Alkaline phosphatase ≤ 5 times ULN AND AST or ALT ≤ ULN

Renal

• Creatinine ≤ 1.5 mg/dL

Cardiovascular

• No unstable angina
• No uncontrolled hypertension
• No myocardial infarction within the past 6 months (unless successfully treated with coronary artery bypass surgery or percutaneous transluminal coronary angioplasty)
• No uncontrolled arrhythmia
• No congestive heart failure
• No more than 2 heart-related hospitalizations within the past year
• No other active cardiac disease

Pulmonary

• No more than 2 hospitalizations for chronic obstructive pulmonary disease within the past year

Neurologic

• No pre-existing peripheral neuropathy ≥ grade 2
• No uncontrolled seizure disorder
• No active neurological disease

Other

• No prior severe hypersensitivity reaction to docetaxel or other drugs formulated with polysorbate 80
• No other invasive malignancy within the past 3 years except nonmelanoma skin cancer
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 3 months after study participation

PRIOR CONCURRENT THERAPY:

Biologic therapy

• No prior anti-epidermal growth factor receptor antibody therapy

Chemotherapy

• More than 3 years since prior cytotoxic chemotherapy

Endocrine therapy

• Not specified

Radiotherapy

• No prior head and neck radiotherapy

Surgery

• See Disease Characteristics

Other

• No prior tyrosine kinase inhibitor therapy

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
Experimental: RT + cisplatin + cetuximab; Loading dose of cetuximab followed by radiation therapy with weekly cisplatin and cetuximab.	Biological: cetuximab; 400 mg/m^2 intravenously over 120 minutes on day 1 (week 1) followed by 250 mg/m^2 intravenously over 60 minutes in weeks 2 through 7.; Drug: cisplatin; 30 mg/m^2 intravenously infused over over 60 minutes in weeks 2 through 7.; Radiation: radiation therapy; 60 Gy (2 Gy once a day, 5 times a week)
Experimental: RT + docetaxel + cetuximab; Loading dose of cetuximab followed by radiation therapy (RT) with weekly docetaxel and cetuximab.	Biological: cetuximab; 400 mg/m^2 intravenously over 120 minutes on day 1 (week 1) followed by 250 mg/m^2 intravenously over 60 minutes in weeks 2 through 7.; Radiation: radiation therapy; 60 Gy (2 Gy once a day, 5 times a week); Drug: docetaxel; 15 mg/m^2 intravenously infused over 30 minutes in weeks 2 through 7.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease-free Survival	Two-year rates are shown (Kaplan-Meier estimates). Disease-free survival is defined as the time from randomization to local, regional, or distant progression, second primary, or death (event) or last follow-up (censored). Response criteria as follows: No evidence of disease (NED): All patients must have no measurable tumor following surgery; Local-Regional Relapse: Recurrent cancer in the tumor bed and/or neck not clearly attributable to a second primary neoplasm; biopsy confirmation is necessary; Distant Relapse: Clear evidence of distant metastases (lung, bone, brain, etc.); Biopsy is recommended where possible. A solitary lung mass/nodule is considered a second primary neoplasm unless proven otherwise.	From randomization to 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival	Two-year rates are shown (Kaplan-Meier estimates). Overall survival is defined as the time from randomization to death (event) or last follow-up (censored).	From randomization to 2 years
Treatment Tolerance	Tolerability was defined as having received 90% of the radiation dose, 95% of the cetuximab loading dose, and at least 4 weeks of cetuximab and cisplatin or docetaxel at doses 95% of the protocol prescription. The percentage of patients determined to be tolerant of treatment are shown.	From start of treatment to end of treatment (protocol treatment lasts seven weeks).
Frequency of Toxicity (Grade 5 and Acute Non-hematologic Grade 4)	Each regimen was monitored for excessive acute toxicity (defined as nonhematologic grade 4 toxicity within 90 days of the start of radiation or any grade 5 toxicity). The target rate was based on the observed rate from RTOG-9501/NCT00002670 of 15%. The unacceptable rate was >30%. [RTOG = Radiation Therapy Oncology Group]	From start of treatment to last follow-up. Analysis occurs at the time of the primary analysis.
Frequency of Other Acute and Late Toxicity	Maximum grade toxicity that is definitely, probably, or possibly related to protocol treatment.	From start of treatment to last follow-up. Analysis occurs at the time of the primary endpoint analysis.
Local-regional Control	Two-year rate is shown (cumulative incidence estimate). Local-regional failure is defined as the time from randomization to local-regional recurrence (event), death (competing risk), or last follow-up (censored).	From randomization to 2 years
Correlation of EGFR (Total and Phosphorylated) pMAPK, pAKT, Stat-3, KI-67, COX-2, and Cyclin B1 Expression With Local-regional Control, and Overall and Disease-free Survival		From randomization to two years

Collaborators and Investigators

• Sponsor: Radiation Therapy Oncology Group
• Collaborators: National Cancer Institute (NCI); NRG Oncology
• Investigators: Principal Investigator: Paul M. Harari, MD, University of Wisconsin, Madison; Study Chair: Jeffrey N. Myers, MD, PhD, FACS, M.D. Anderson Cancer Center

Publications and helpful links

General Publications

• Harari PM, Harris J, Kies MS, et al.: Phase II randomized trial of surgery followed by chemoradiation plus cetuximab for high-risk squamous cell carcinoma of the head and neck (RTOG 0234). [Abstract] Int J Radiat Oncol Biol Phys 69 (3 Suppl): A-22, S13, 2007.
• Harari PM, Harris J, Kies MS, Myers JN, Jordan RC, Gillison ML, Foote RL, Machtay M, Rotman M, Khuntia D, Straube W, Zhang Q, Ang K. Postoperative chemoradiotherapy and cetuximab for high-risk squamous cell carcinoma of the head and neck: Radiation Therapy Oncology Group RTOG-0234. J Clin Oncol. 2014 Aug 10;32(23):2486-95. doi: 10.1200/JCO.2013.53.9163. Epub 2014 Jul 7.

Study record dates

Study Major Dates

• Study Start: April 1, 2004
• Primary Completion (Actual): March 1, 2009
• Study Completion (Actual): December 1, 2016

Study Registration Dates

• First Submitted: June 10, 2004
• First Submitted That Met QC Criteria: June 10, 2004
• First Posted (Estimate): June 11, 2004

Study Record Updates

• Last Update Posted (Actual): December 12, 2018
• Last Update Submitted That Met QC Criteria: November 15, 2018
• Last Verified: December 1, 2016

More Information

Terms related to this study

• Keywords: stage III squamous cell carcinoma of the oropharynx; stage III lymphoepithelioma of the oropharynx; stage IV squamous cell carcinoma of the oropharynx; stage IV lymphoepithelioma of the oropharynx; stage III squamous cell carcinoma of the hypopharynx; stage IV squamous cell carcinoma of the hypopharynx; stage III squamous cell carcinoma of the larynx; stage IV squamous cell carcinoma of the larynx
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Squamous Cell; Carcinoma; Carcinoma, Squamous Cell; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Immunological; Docetaxel; Cisplatin; Cetuximab
• Other Study ID Numbers: RTOG-0234; CDR0000360850