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
- Conditions
- Head and Neck Cancer
- Interventions
- Registration Number
- NCT00084318
- Lead Sponsor
- Radiation Therapy Oncology Group
- Brief Summary
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.
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 238
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description RT + cisplatin + cetuximab cetuximab Loading dose of cetuximab followed by radiation therapy with weekly cisplatin and cetuximab. RT + docetaxel + cetuximab cetuximab Loading dose of cetuximab followed by radiation therapy (RT) with weekly docetaxel and cetuximab. RT + cisplatin + cetuximab radiation therapy Loading dose of cetuximab followed by radiation therapy with weekly cisplatin and cetuximab. RT + docetaxel + cetuximab radiation therapy Loading dose of cetuximab followed by radiation therapy (RT) with weekly docetaxel and cetuximab. RT + cisplatin + cetuximab cisplatin Loading dose of cetuximab followed by radiation therapy with weekly cisplatin and cetuximab. RT + docetaxel + cetuximab docetaxel Loading dose of cetuximab followed by radiation therapy (RT) with weekly docetaxel and cetuximab.
- Primary Outcome Measures
Name Time Method Disease-free Survival From randomization to 2 years 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.
- Secondary Outcome Measures
Name Time Method Frequency of Toxicity (Grade 5 and Acute Non-hematologic Grade 4) From start of treatment to last follow-up. Analysis occurs at the time of the primary analysis. 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%. \[RTOG = Radiation Therapy Oncology Group\]
Frequency of Other Acute and Late Toxicity From start of treatment to last follow-up. Analysis occurs at the time of the primary endpoint analysis. Maximum grade toxicity that is definitely, probably, or possibly related to protocol treatment.
Overall Survival From randomization to 2 years 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).
Treatment Tolerance From start of treatment to end of treatment (protocol treatment lasts seven weeks). 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.
Local-regional Control From randomization to 2 years 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).
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
Trial Locations
- Locations (160)
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
🇺🇸Baltimore, Maryland, United States
Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University
🇺🇸Columbus, Ohio, United States
Charles M. Barrett Cancer Center at University Hospital
🇺🇸Cincinnati, Ohio, United States
Virginia Piper Cancer Institute at Abbott-Northwestern Hospital
🇺🇸Minneapolis, Minnesota, United States
University of Minnesota Medical Center & Children's Hospital - Fairview
🇺🇸Minneapolis, Minnesota, United States
Saint Peter's University Hospital
🇺🇸New Brunswick, New Jersey, United States
Radiation Oncology Centers - Cameron Park
🇺🇸Cameron Park, California, United States
Loma Linda University Cancer Institute at Loma Linda University Medical Center
🇺🇸Loma Linda, California, United States
CCOP - Bay Area Tumor Institute
🇺🇸Oakland, California, United States
Mercy Cancer Center at Mercy San Juan Medical Center
🇺🇸Carmichael, California, United States
University of Miami Sylvester Comprehensive Cancer Center
🇺🇸Miami, Florida, United States
Providence Saint Joseph Medical Center - Burbank
🇺🇸Burbank, California, United States
CCOP - Grand Rapids
🇺🇸Grand Rapids, Michigan, United States
Lacks Cancer Center at Saint Mary's Health Care
🇺🇸Grand Rapids, Michigan, United States
Michael & Dianne Bienes Comprehensive Cancer Center at Holy Cross Hospital
🇺🇸Fort Lauderdale, Florida, United States
Radiation Oncology Center - Roseville
🇺🇸Roseville, California, United States
Solano Radiation Oncology Center
🇺🇸Vacaville, California, United States
Curtis & Elizabeth Anderson Cancer Institute at Memorial Health University Medical Center
🇺🇸Savannah, Georgia, United States
Saint Anthony's Hospital at Saint Anthony's Health Center
🇺🇸Alton, Illinois, United States
Mayo Clinic - Jacksonville
🇺🇸Jacksonville, Florida, United States
CCOP - Northern Indiana CR Consortium
🇺🇸South Bend, Indiana, United States
Tulane Cancer Center
🇺🇸Alexandria, Louisiana, United States
CCOP - Christiana Care Health Services
🇺🇸Newark, Delaware, United States
Cardinal Bernardin Cancer Center at Loyola University Medical Center
🇺🇸Maywood, Illinois, United States
Ingalls Cancer Care Center at Ingalls Memorial Hospital
🇺🇸Harvey, Illinois, United States
Massachusetts General Hospital Cancer Center
🇺🇸Boston, Massachusetts, United States
Baptist Cancer Institute - Jacksonville
🇺🇸Jacksonville, Florida, United States
Ella Milbank Foshay Cancer Center at Jupiter Medical Center
🇺🇸Jupiter, Florida, United States
Tallahassee Memorial Hospital
🇺🇸Tallahassee, Florida, United States
Genesys Hurley Cancer Institute
🇺🇸Flint, Michigan, United States
Dana-Farber/Brigham and Women's Cancer Center
🇺🇸Boston, Massachusetts, United States
Wendt Regional Cancer Center at Finley Hospital
🇺🇸Dubuque, Iowa, United States
Northeast Georgia Medical Center
🇺🇸Gainesville, Georgia, United States
Good Samaritan Regional Health Center
🇺🇸Mount Vernon, Illinois, United States
John B. Amos Cancer Center
🇺🇸Columbus, Georgia, United States
Elkhart General Hospital
🇺🇸Elkhart, Indiana, United States
Cancer Institute at St. John's Hospital
🇺🇸Springfield, Illinois, United States
Cancer Research Center at Boston Medical Center
🇺🇸Boston, Massachusetts, United States
Center for Cancer Therapy at LaPorte Hospital and Health Services
🇺🇸La Porte, Indiana, United States
Fairview Ridges Hospital
🇺🇸Burnsville, Minnesota, United States
Mercy and Unity Cancer Center at Mercy Hospital
🇺🇸Coon Rapids, Minnesota, United States
Upper Michigan Cancer Center at Marquette General Hospital
🇺🇸Marquette, Michigan, United States
Lakeland Cancer Care Center at Lakeland Hospital - St. Joseph
🇺🇸Saint Joseph, Michigan, United States
West Michigan Cancer Center
🇺🇸Kalamazoo, Michigan, United States
Hurley Medical Center
🇺🇸Flint, Michigan, United States
Fairview Southdale Hospital
🇺🇸Edina, Minnesota, United States
CCOP - Metro-Minnesota
🇺🇸Saint Louis Park, Minnesota, United States
CentraCare Clinic - River Campus
🇺🇸Saint Cloud, Minnesota, United States
Coborn Cancer Center
🇺🇸Saint Cloud, Minnesota, United States
Regional Cancer Center at Singing River Hospital
🇺🇸Pascagoula, Mississippi, United States
United Hospital
🇺🇸Saint Paul, Minnesota, United States
Hulston Cancer Center at Cox Medical Center South
🇺🇸Springfield, Missouri, United States
Park Nicollet Health Services
🇺🇸Saint Louis Park, Minnesota, United States
Long Island College Hospital
🇺🇸Brooklyn, New York, United States
Mission Hospitals - Memorial Campus
🇺🇸Asheville, North Carolina, United States
Blumenthal Cancer Center at Carolinas Medical Center
🇺🇸Charlotte, North Carolina, United States
Siteman Cancer Center at Barnes-Jewish Hospital
🇺🇸Saint Louis, Missouri, United States
Saint Francis Medical Center
🇺🇸Cape Girardeau, Missouri, United States
CCOP - St. Louis-Cape Girardeau
🇺🇸Saint Louis, Missouri, United States
Wayne Memorial Hospital, Incorporated
🇺🇸Goldsboro, North Carolina, United States
Bryn Mawr Hospital
🇺🇸Bryn Mawr, Pennsylvania, United States
Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center
🇺🇸Lebanon, New Hampshire, United States
York Cancer Center at Apple Hill Medical Center
🇺🇸York, Pennsylvania, United States
Akron City Hospital
🇺🇸Akron, Ohio, United States
Iredell Memorial Hospital
🇺🇸Statesville, North Carolina, United States
SUNY Upstate Medical University Hospital
🇺🇸Syracuse, New York, United States
McDowell Cancer Center at Akron General Medical Center
🇺🇸Akron, Ohio, United States
Leo W. Jenkins Cancer Center at ECU Medical School
🇺🇸Greenville, North Carolina, United States
Hillcrest Cancer Center at Hillcrest Hospital
🇺🇸Mayfield Heights, Ohio, United States
Rosenfeld Cancer Center at Abington Memorial Hospital
🇺🇸Abington, Pennsylvania, United States
Dale and Frances Hughes Cancer Center at Pocono Medical Center
🇺🇸East Stroudsburg, Pennsylvania, United States
Fox Chase Cancer Center - Philadelphia
🇺🇸Philadelphia, Pennsylvania, United States
Kimmel Cancer Center at Thomas Jefferson University - Philadelphia
🇺🇸Philadelphia, Pennsylvania, United States
Cancer Center of Paoli Memorial Hospital
🇺🇸Paoli, Pennsylvania, United States
Penn State Cancer Institute at Milton S. Hershey Medical Center
🇺🇸Hershey, Pennsylvania, United States
Lankenau Cancer Center at Lankenau Hospital
🇺🇸Wynnewood, Pennsylvania, United States
M.D. Anderson Cancer Center at University of Texas
🇺🇸Houston, Texas, United States
McKay-Dee Hospital Center
🇺🇸Ogden, Utah, United States
CCOP - Scott and White Hospital
🇺🇸Temple, Texas, United States
Dixie Regional Medical Center - East Campus
🇺🇸Saint George, Utah, United States
Cottonwood Hospital Medical Center
🇺🇸Murray, Utah, United States
Utah Cancer Specialists at UCS Cancer Center
🇺🇸Salt Lake City, Utah, United States
University Cancer Center at University of Washington Medical Center
🇺🇸Seattle, Washington, United States
Green Bay Oncology, Limited at St. Vincent Hospital
🇺🇸Green Bay, Wisconsin, United States
Huntsman Cancer Institute at University of Utah
🇺🇸Salt Lake City, Utah, United States
Danville Regional Medical Center
🇺🇸Danville, Virginia, United States
Schiffler Cancer Center at Wheeling Hospital
🇺🇸Wheeling, West Virginia, United States
Green Bay Oncology, Limited at St. Mary's Hospital
🇺🇸Green Bay, Wisconsin, United States
CCOP - Virginia Mason Research Center
🇺🇸Seattle, Washington, United States
St. Joseph Cancer Center
🇺🇸Bellingham, Washington, United States
Gundersen Lutheran Cancer Center at Gundersen Lutheran Medical Center
🇺🇸La Crosse, Wisconsin, United States
St. Vincent Hospital Regional Cancer Center
🇺🇸Green Bay, Wisconsin, United States
Bay Area Cancer Care Center at Bay Area Medical Center
🇺🇸Marinette, Wisconsin, United States
Josephine Ford Cancer Center at Henry Ford Hospital
🇺🇸Detroit, Michigan, United States
University of Alabama at Birmingham Comprehensive Cancer Center
🇺🇸Birmingham, Alabama, United States
Oregon Health & Science University Cancer Institute
🇺🇸Portland, Oregon, United States
University of Colorado Cancer Center at University of Colorado Health Sciences Center
🇺🇸Aurora, Colorado, United States
Mayo Clinic Cancer Center
🇺🇸Rochester, Minnesota, United States
Methodist Cancer Center at Methodist Hospital - Omaha
🇺🇸Omaha, Nebraska, United States
Medical College of Wisconsin Cancer Center
🇺🇸Milwaukee, Wisconsin, United States
St. John's Regional Health Center
🇺🇸Springfield, Missouri, United States
Latter Day Saints Hospital
🇺🇸Salt Lake City, Utah, United States
Utah Valley Regional Medical Center - Provo
🇺🇸Provo, Utah, United States
Ridgeview Medical Center
🇺🇸Waconia, Minnesota, United States
Borgess Medical Center
🇺🇸Kalamazoo, Michigan, United States
Bronson Methodist Hospital
🇺🇸Kalamazoo, Michigan, United States
H. Lee Moffitt Cancer Center and Research Institute at University of South Florida
🇺🇸Tampa, Florida, United States
Torrance Memorial Medical Center
🇺🇸Torrance, California, United States
Mercy Cancer Institute at Mercy Hospital
🇺🇸Pittsburgh, Pennsylvania, United States
Radiological Associates of Sacramento Medical Group, Incorporated
🇺🇸Sacramento, California, United States
University of California Davis Cancer Center
🇺🇸Sacramento, California, United States
Mercy General Hospital
🇺🇸Sacramento, California, United States
St. Joseph Mercy Cancer Center at St. Joseph Mercy Hospital
🇺🇸Ann Arbor, Michigan, United States
Forsyth Regional Cancer Center at Forsyth Medical Center
🇺🇸Winston-Salem, North Carolina, United States
Auburn Radiation Oncology
🇺🇸Auburn, California, United States
Hudner Oncology Center at Saint Anne's Hospital - Fall River
🇺🇸Fall River, Massachusetts, United States
Mobile Infirmary Medical Center
🇺🇸Mobile, Alabama, United States
Lynn Regional Cancer Center at Boca Raton Community Hospital - Main Center
🇺🇸Boca Raton, Florida, United States
Memorial Hospital of South Bend
🇺🇸South Bend, Indiana, United States
Mercy and Unity Cancer Center at Unity Hospital
🇺🇸Fridley, Minnesota, United States
Southeast Missouri Regional Cancer Center at Southeast Missouri Hospital
🇺🇸Cape Girardeau, Missouri, United States
Roswell Park Cancer Institute
🇺🇸Buffalo, New York, United States
David C. Pratt Cancer Center at St. John's Mercy
🇺🇸Saint Louis, Missouri, United States
Cancer Institute of New Jersey at Cooper University Hospital - Camden
🇺🇸Camden, New Jersey, United States
J. Phillip Citta Regional Cancer Center at Community Medical Center
🇺🇸Toms River, New Jersey, United States
Hubert H. Humphrey Cancer Center at North Memorial Medical Center
🇺🇸Robbinsdale, Minnesota, United States
Mount Nittany Medical Center
🇺🇸State College, Pennsylvania, United States
Guthrie Cancer Center at Guthrie Clinic Sayre
🇺🇸Sayre, Pennsylvania, United States
Reading Hospital and Medical Center
🇺🇸Reading, Pennsylvania, United States
CCOP - MainLine Health
🇺🇸Wynnewood, Pennsylvania, United States
Bon Secours St. Francis Health System
🇺🇸Greenville, South Carolina, United States
Gibbs Regional Cancer Center at Spartanburg Regional Medical Center
🇺🇸Spartanburg, South Carolina, United States
Rapid City Regional Hospital
🇺🇸Rapid City, South Dakota, United States
St. Mary's Hospital Medical Center - Green Bay
🇺🇸Green Bay, Wisconsin, United States
All Saints Cancer Center at All Saints Healthcare
🇺🇸Racine, Wisconsin, United States
Hospital of Saint Raphael
🇺🇸New Haven, Connecticut, United States
M.D. Anderson Cancer Center Orlando
🇺🇸Orlando, Florida, United States
CCOP - Kansas City
🇺🇸Kansas City, Missouri, United States
Hollings Cancer Center at Medical University of South Carolina
🇺🇸Charleston, South Carolina, United States
Christine LaGuardia Phillips Cancer Center at Wellmont Holston Valley Medical Center
🇺🇸Kingsport, Tennessee, United States
Arizona Oncology Services Foundation
🇺🇸Phoenix, Arizona, United States
Virginia G. Piper Cancer Center at Scottsdale Healthcare - Osborn
🇺🇸Scottsdale, Arizona, United States
Memorial Sloan-Kettering Cancer Center
🇺🇸New York, New York, United States
CCOP - Greenville
🇺🇸Greenville, South Carolina, United States
CCOP - Upstate Carolina
🇺🇸Spartanburg, South Carolina, United States
Fox Chase Virtua Health Cancer Program at Virtua West Jersey
🇺🇸Voorhees, New Jersey, United States
Fox Chase Virtua Health Cancer Program at Virtua Memorial Hospital Marlton
🇺🇸Marlton, New Jersey, United States
Thompson Cancer Survival Center
🇺🇸Knoxville, Tennessee, United States
John D. Cronin Cancer Center
🇺🇸Lexington, Kentucky, United States
Markey Cancer Center at University of Kentucky Chandler Medical Center
🇺🇸Lexington, Kentucky, United States
Veterans Affairs Medical Center - Richmond
🇺🇸Richmond, Virginia, United States
Virginia Commonwealth University Massey Cancer Center
🇺🇸Richmond, Virginia, United States
University of Wisconsin Comprehensive Cancer Center
🇺🇸Madison, Wisconsin, United States
Virginia G. Piper Cancer Center at Scottsdale Healthcare - Shea
🇺🇸Scottsdale, Arizona, United States
Mayo Clinic Scottsdale
🇺🇸Scottsdale, Arizona, United States
CCOP - Mount Sinai Medical Center
🇺🇸Miami Beach, Florida, United States
Good Samaritan Cancer Center at Good Samaritan Hospital
🇺🇸Kearney, Nebraska, United States
Providence Holy Cross Cancer Center
🇺🇸Mission Hills, California, United States
Veterans Affairs Medical Center - East Orange
🇺🇸East Orange, New Jersey, United States