A Phase III Study of Postoperative Radiation Therapy (IMRT) +/- Cetuximab for Locally-Advanced Resected Head and Neck Cancer
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.
Interventional
Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Overall survival
From randomization to date of death or last follow-up. Analysis occurs after 372 events have been reported.
No
Mitchell Machtay, MD
Study Chair
University Hospitals Seidman Cancer Center
United States: Food and Drug Administration
RTOG 0920
NCT00956007
November 2009
Name | Location |
---|---|
Memorial Sloan-Kettering Cancer Center | New York, New York 10021 |
University of Michigan Comprehensive Cancer Center | Ann Arbor, Michigan 48109-0752 |
Mayo Clinic Cancer Center | Rochester, Minnesota 55905 |
Cardinal Bernardin Cancer Center at Loyola University Medical Center | Maywood, Illinois 60153-5500 |
University of Texas Health Science Center at San Antonio | San Antonio, Texas 78284-7811 |
CCOP - Christiana Care Health Services | Wilmington, Delaware 19899 |
CCOP - Carle Cancer Center | Urbana, Illinois 61801 |
Penrose Cancer Center at Penrose Hospital | Colorado Springs, Colorado 80933 |
Porter Adventist Hospital | Denver, Colorado 80210 |
Siouxland Hematology-Oncology Associates, LLP | Sioux City, Iowa 51101 |
West Michigan Cancer Center | Kalamazoo, Michigan 49007-3731 |
Mercy and Unity Cancer Center at Mercy Hospital | Coon Rapids, Minnesota 55433 |
Mercy and Unity Cancer Center at Unity Hospital | Fridley, Minnesota 55432 |
Mercy Cancer Center at Mercy Medical Center | Canton, Ohio 44708 |
Case Comprehensive Cancer Center | Cleveland, Ohio 44106-5065 |
MetroHealth Cancer Care Center at MetroHealth Medical Center | Cleveland, Ohio 44109 |
Vanderbilt-Ingram Cancer Center | Nashville, Tennessee 37232-6838 |
University of Wisconsin Paul P. Carbone Comprehensive Cancer Center | Madison, Wisconsin 53792-6164 |
Medical College of Wisconsin Cancer Center | Milwaukee, Wisconsin 53226 |
Rapid City Regional Hospital | Rapid City, South Dakota 57709 |
Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill | Chapel Hill, North Carolina 27599-7570 |
Charles M. Barrett Cancer Center at University Hospital | Cincinnati, Ohio 45267-0526 |
CCOP - Columbia River Oncology Program | Portland, Oregon 97225 |
Kimmel Cancer Center at Thomas Jefferson University - Philadelphia | Philadelphia, Pennsylvania 19107 |
Cancer Research Center of Hawaii | Honolulu, Hawaii 96813 |
Cleveland Clinic Taussig Cancer Center | Cleveland, Ohio 44195 |
Veterans Affairs Medical Center - Portland | Portland, Oregon 97207 |
CCOP - Northwest | Tacoma, Washington 98405-0986 |
Veterans Affairs Medical Center - Richmond | Richmond, Virginia 23249 |
Rebecca and John Moores UCSD Cancer Center | La Jolla, California 92093-0658 |
University of California Davis Cancer Center | Sacramento, California 95817 |
City of Hope Comprehensive Cancer Center | Duarte, California 91010 |
Kansas Masonic Cancer Research Institute at the University of Kansas Medical Center | Kansas City, Kansas 66160-7353 |
James Graham Brown Cancer Center at University of Louisville | Louisville, Kentucky 40202 |
Hulston Cancer Center at Cox Medical Center South | Springfield, Missouri 65807 |
McDowell Cancer Center at Akron General Medical Center | Akron, Ohio 44307 |
Lake/University Ireland Cancer Center | Mentor, Ohio 44060 |
Yale Cancer Center | New Haven, Connecticut 06520-8028 |
Florida Hospital Cancer Institute at Florida Hospital Orlando | Orlando, Florida 32803-1273 |
Winship Cancer Institute of Emory University | Atlanta, Georgia 30322 |
Mission Hospitals - Memorial Campus | Asheville, North Carolina 28801 |
Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas | Dallas, Texas 75390 |
Lahey Clinic Medical Center - Burlington | Burlington, Massachusetts 01805 |
Saint Peter's University Hospital | New Brunswick, New Jersey 08901-1780 |
James P. Wilmot Cancer Center at University of Rochester Medical Center | Rochester, New York 14642 |
Utah Cancer Specialists at UCS Cancer Center | Salt Lake City, Utah 84106 |
Cancer Care Northwest - Spokane South | Spokane, Washington 99202 |
UCSF Helen Diller Family Comprehensive Cancer Center | San Francisco, California 94115 |
Lucille P. Markey Cancer Center at University of Kentucky | Lexington, Kentucky 40536-0093 |
Tulane Cancer Center Office of Clinical Research | Alexandria, Louisiana 71315-3198 |
Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis | St. Louis, Missouri 63110 |
University of New Mexico Cancer Center | Albuquerque, New Mexico 87131-5636 |
Beth Israel Medical Center - Petrie Division | New York, New York 10003-3803 |
Oklahoma University Cancer Institute | Oklahoma City, Oklahoma 73104 |
Knight Cancer Institute at Oregon Health and Science University | Portland, Oregon 97239-3098 |
M. D. Anderson Cancer Center at University of Texas | Houston, Texas 77030-4009 |
Virginia Commonwealth University Massey Cancer Center | Richmond, Virginia 23298-0037 |
Methodist Estabrook Cancer Center | Omaha, Nebraska 68114-4199 |
Huntsman Cancer Institute at University of Utah | Salt Lake City, Utah 84112 |
Cleveland Clinic Cancer Center at Fairview Hospital | Cleveland, Ohio 44111 |
Hillcrest Cancer Center at Hillcrest Hospital | Mayfield Heights, Ohio 44124 |
Morgan Cancer Center at Lehigh Valley Hospital - Cedar Crest | Allentown, Pennsylvania 18105 |
Fox Chase Cancer Center - Philadelphia | Philadelphia, Pennsylvania 19111-2497 |
Fox Valley Hematology and Oncology - East Grant Street | Appleton, Wisconsin 54911-3496 |
Saint Alphonsus Cancer Care Center at Saint Alphonsus Regional Medical Center | Boise, Idaho 83706 |
Ingalls Cancer Care Center at Ingalls Memorial Hospital | Harvey, Illinois 60426 |
Highland Hospital of Rochester | Rochester, New York 14620 |
St. Charles Mercy Hospital | Oregon, Ohio 43616 |
North Coast Cancer Care, Incorporated | Sandusky, Ohio 44870 |
Providence Cancer Center at Providence Portland Medical Center | Portland, Oregon 97213-2967 |
Providence St. Vincent Medical Center | Portland, Oregon 97225 |
Dixie Regional Medical Center - East Campus | Saint George, Utah 84770 |
Southwest Washington Medical Center Cancer Center | Vancouver, Washington 98668 |
William W. Backus Hospital | Norwich, Connecticut 06360 |
Cancer Center at Ball Memorial Hospital | Muncie, Indiana 47303 |
Regional Cancer Center at Singing River Hospital | Pascagoula, Mississippi 39581 |
Missouri Baptist Cancer Center | St. Louis, Missouri 63131 |
UAB Comprehensive Cancer Center | Birmingham, Alabama 35294 |
Nancy N. and J. C. Lewis Cancer and Research Pavilion at St. Joseph's/Candler | Savannah, Georgia 31405 |
McFarland Clinic, PC | Ames, Iowa 50010 |
Seton Cancer Institute at Saint Mary's - Saginaw | Saginaw, Michigan 48601 |
Frederick R. and Betty M. Smith Cancer Treatment Center | Sparta, New Jersey 07871 |
Summa Center for Cancer Care at Akron City Hospital | Akron, Ohio 44309-2090 |
Barberton Citizens Hospital | Barberton, Ohio 44203 |
Arthur G. James Cancer Hospital and Richard J. Solove Research Institute at Ohio State University Comprehensive Cancer Center | Columbus, Ohio 43210-1240 |
Flower Hospital Cancer Center | Sylvania, Ohio 43560 |
Legacy Good Samaritan Hospital & Comprehensive Cancer Center | Portland, Oregon 97210 |
Salem Hospital Regional Cancer Care Services | Salem, Oregon 97309-5014 |
McGlinn Family Regional Cancer Center at Reading Hospital and Medical Center | Reading, Pennsylvania 19612-6052 |
York Cancer Center at Apple Hill Medical Center | York, Pennsylvania 17405 |
Radiological Associates of Sacramento Medical Group, Incorporated | Sacramento, California 95815 |
St. Vincent's Medical Center | Bridgeport, Connecticut 06606 |
Queen's Cancer Institute at Queen's Medical Center | Honolulu, Hawaii 96813 |
Parkview Regional Cancer Center at Parkview Health | Fort Wayne, Indiana 46805 |
Gibbs Regional Cancer Center at Spartanburg Regional Medical Center | Spartanburg, South Carolina 29303 |
Kinston Medical Specialists | Kinston, North Carolina 28501 |
Regional Cancer Center - Erie | Erie, Pennsylvania 16505 |
Cancer Institute at St. John's Hospital | Springfield, Illinois 62701 |
Sentara Cancer Institute at Sentara Norfolk General Hospital | Norfolk, Virginia 23507 |
Solano Radiation Oncology Center | Vacaville, California 95687 |
Boston University Cancer Research Center | Boston, Massachusetts 02118 |
Mercy General Hospital | Sacramento, California 95819 |
Memorial Medical Center | Modesto, California 95355 |
Hawaii Medical Center - East | Honolulu, Hawaii 96817 |
Center for Cancer Care at Exeter Hospital | Exeter, New Hampshire 03833 |
Dale and Frances Hughes Cancer Center at Pocono Medical Center | East Stroudsburg, Pennsylvania 18301 |
University of Colorado Cancer Center at UC Health Sciences Center | Aurora, Colorado 80045 |
Center for Cancer Care at Goshen General Hospital | Goshen, Indiana 46526 |
Cancer Institute of Cape Girardeau, LLC | Cape Girardeau, Missouri 63703 |
Veterans Affairs Medical Center - Milwaukee | Milwaukee, Wisconsin 53295 |
Cancer Centers of North Carolina - Raleigh | Raleigh, North Carolina 27607 |
Precision Radiotherapy at University Pointe | West Chester, Ohio 45069 |
Central Maine Comprehensive Cancer Center at Central Maine Medical Center | Lewiston, Maine 04240 |
Minnesota Oncology - Maplewood | Maplewood, Minnesota 55109 |
Emory Crawford Long Hospital | Atlanta, Georgia 30308 |
New York Oncology Hematology, PC at Albany Regional Cancer Care | Albany, New York 12208 |
Auburn Radiation Oncology | Auburn, California 95603 |
Radiation Oncology Centers - Cameron Park | Cameron Park, California 95682 |
Radiation Oncology Center - Roseville | Roseville, California 95661 |
Bassett Healthcare Regional Cancer Program at Mary Imogene Bassett Hospital | Cooperstown, New York 13326 |
Northwest Cancer Specialists at Vancouver Cancer Center | Vancouver, Washington 98684 |
Mercy Cancer Center at Mercy San Juan Medical Center | Carmichael, California 95608 |
Barnes-Jewish West County Hospital | Saint Louis, Missouri 63141 |
Siteman Cancer Center at Barnes-Jewish St. Peters Hospital - St. Peters | Saint Peters, Missouri 63376 |
Renown Institute for Cancer at Renown Regional Medical Center | Reno, Nevada 89502 |
Sands Cancer Center | Canandiaqua, New York 14424 |
University Radiation Oncology at Parkridge Hospital | Rochester, New York 14626 |
Community Regional Cancer Care at Community Hospital North | Indianapolis, Indiana 46256 |
Community Regional Cancer Care at Community Hospital East | Indianapolis, Indiana 46219 |
Langlade Memorial Hospital | Antigo, Wisconsin 54409 |
Southwest General Health Center | Middleburgh Heights, Ohio 44130 |
Clackamas Radiation Oncology Center | Clackamas, Oregon 97015 |
Saint Helena Hospital | Saint Helena, California 94574 |
Radiation Oncology Associates Southwest | Fort Wayne, Indiana 46804 |
Willamette Valley Cancer Center - Eugene | Eugene, Oregon 97401 |
Texas Oncology, PA at Harris Center HEB | Bedford, Texas 76022 |
Texas Oncology, PA at Texas Cancer Center - Denton South | Denton, Texas 76210 |
Klabzuba Cancer Center at Harris Methodist Fort Worth Hospital | Fort Worth, Texas 76104 |
Cancer Care Centers of South Texas - Northeast | San Antonio, Texas 78217 |
Texas Oncology, PA at Texas Cancer Center - Sherman | Sherman, Texas 75090 |
Texas Oncology, PA at Texas Oncology Cancer Center Sugar Land | Sugar Land, Texas 77479 |
Memorial Sloan-Kettering Cancer Center at Phelps Memorial Hospital Center | Sleepy Hollow, New York 10591 |
Nebraska Medical Center | Omaha, Nebraska 68198 |
Arizona Oncology - Tucson | Tucson, Arizona 85704 |
Rocky Mountain Cancer Centers - Aurora | Aurora, Colorado 80012 |
Adams Cancer Center | Gettysburg, Pennsylvania 17325 |
Robinson Radiation Oncology | Ravenna, Ohio 44266 |
Saint Elizabeth Cancer Institute at Saint Elizabeth Regional Medical Center | Lincoln, Nebraska 68510 |
Coastal Cancer Center at Sentara Virginia Beach General Hospital | Virginia Beach, Virginia 23454 |
Memorial Sloan-Kettering Cancer Center - Basking Ridge | Basking Ridge, New Jersey 07920 |
Memorial Sloan-Kettering Cancer Center - Rockville Centre | Rockville Centre, New York 11570 |
Memorial Hermann Hospital - Memorial City | Houston, Texas 77024 |
Texas Oncology, PA - Wichita Falls | Wichita Falls, Texas 76310 |