Chemotherapy and Radiation Therapy With or Without Surgery in Treating Patients With Head and Neck Cancer

A Phase III Trial of Concurrent Radiation and Chemotherapy for Advanced Head and Neck Carcinomas

RATIONALE: Radiation therapy (RT) uses high-energy x-rays to damage tumor cells. Giving radiation therapy in different ways and combining it with chemotherapy before surgery may kill more tumor cells. It is not yet known which radiation therapy regimen combined with chemotherapy with or without surgery is more effective for head and neck cancer.

PURPOSE: Randomized phase III trial to compare two different radiation therapy regimens combined with cisplatin with or without surgery in treating patients who have stage III or stage IV head and neck cancer.

Study Overview

• Status: Completed
• Conditions: Head and Neck Cancer
• Intervention / Treatment: Drug: cisplatin; Radiation: Standard fractionation RT; Procedure: Conventional surgery for select patients; Radiation: Accelerated fractionation radiation therapy

Detailed Description

OBJECTIVES:

Primary

• Compare overall survival of patients with stage III or IV squamous cell carcinoma of the head and neck treated with conventional vs accelerated radiotherapy and concurrent cisplatin with or without surgical resection.

Secondary

• Compare local-regional control of disease and disease-free rates in patients treated with these regimens.
• Compare the acute and late toxicity of these regimens in these patients.
• Compare quality of life, perception of side effects, and performance status of patients treated with these regimens.
• Determine whether epidermal growth factor receptor and cyclo-oxygenase-2 expressions are independent prognostic markers in patients treated with these regimens.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to tumor site (larynx vs other), nodal stage (N0 vs N1 or N2a or N2b vs N2c or N3), and Zubrod performance status (0 vs 1). Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients undergo standard fractionation radiotherapy 5 days a week for 7 weeks. Patients also receive cisplatin IV on days 1, 22, and 43.
• Arm II: Patients undergo accelerated fractionation radiotherapy 5 days a week for 3.5 weeks and then twice a day, 5 days a week, for 2.5 weeks. Patients also receive cisplatin IV on days 1 and 22.

Patients with biopsy-proven relapsed disease more than 3 months after completion of therapy undergo surgical resection of the primary tumor.

Quality of life is assessed at baseline, during one of the last 2 weeks of treatment, at 3 and 12 months, and then annually for 4 years.

Patients are followed at 6-8 weeks, every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 720 patients (360 per treatment arm) will be accrued for this study within 3 years.

• Study Type: Interventional
• Enrollment (Actual): 743
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • Comprehensive Cancer Center at University of Alabama at Birmingham
    • Mobile, Alabama, United States, 36607
      • Mobile Infirmary Medical Center
  • Arizona
    • Phoenix, Arizona, United States, 85013
      • Foundation for Cancer Research and Education
    • Scottsdale, Arizona, United States, 85259
      • CCOP - Mayo Clinic Scottsdale Oncology Program
    • Scottsdale, Arizona, United States, 85260
      • Scottsdale Healthcare - Shea
    • Scottsdale, Arizona, United States, 85260
      • Virginia G. Piper Cancer Center at Scottsdale Healthcare - Osborn
  • California
    • Burbank, California, United States, 91505
      • Providence Saint Joseph Medical Center - Burbank
    • Hayward, California, United States, 94545
      • Saint Rose Hospital
    • Inglewood, California, United States, 90301
      • Cancer Care Consultants Medical Associates at Daniel Freeman Memorial Hospital
    • Livermore, California, United States, 94550
      • Valley Memorial Hospital
    • Loma Linda, California, United States, 92354
      • Loma Linda University Cancer Institute at Loma Linda University Medical Center
    • Los Angeles, California, United States, 90033-0804
      • USC/Norris Comprehensive Cancer Center and Hospital
    • Mission Hills, California, United States, 91346-9600
      • Providence Holy Cross Cancer Center
    • Oakland, California, United States, 94602
      • Highland General Hospital
    • Oakland, California, United States, 94609
      • CCOP - Bay Area Tumor Institute
    • Oakland, California, United States, 94609
      • Summit Medical Center
    • Pomona, California, United States, 91767
      • Pomona Valley Hospital Medical Center
    • Sacramento, California, United States, 95817
      • University of California Davis Cancer Center
    • Sacramento, California, United States, 95815
      • Radiological Associates of Sacramento Medical Group, Inc.
    • San Diego, California, United States, 92134
      • Naval Medical Center - San Diego
    • San Pablo, California, United States, 94806
      • J.C. Robinson, M.D. Regional Cancer Center
  • Colorado
    • Colorado Springs, Colorado, United States, 80909
      • Memorial Hospital Cancer Center
    • Denver, Colorado, United States, 80217-3364
      • University of Colorado Cancer Center at University of Colorado Health Sciences Center
  • Delaware
    • Lewes, Delaware, United States, 19958
      • Beebe Medical Center
    • Newark, Delaware, United States, 19718
      • CCOP - Christiana Care Health Services
    • Wilmington, Delaware, United States, 19805
      • St. Francis Hospital
  • Florida
    • Fort Lauderdale, Florida, United States, 33308
      • Michael & Dianne Bienes Comprehensive Cancer Center at Holy Cross Hospital
    • Fort Myers, Florida, United States, 33901
      • 21st Century Oncology - Fort Myers
    • Gainesville, Florida, United States, 32610
      • Shands Cancer Center at the University of Florida - Jacksonville
    • Hollywood, Florida, United States, 33021
      • Memorial Cancer Institute at Memorial Regional Hospital
    • Jacksonville, Florida, United States, 32207
      • Baptist Cancer Institute - Jacksonville
    • Jacksonville, Florida, United States, 32209
      • University of Florida Shands Cancer Center
    • Jupiter, Florida, United States, 33458
      • Ella Milbank Foshay Cancer Center at Jupiter Medical Center
    • Miami Beach, Florida, United States, 33140
      • CCOP - Mount Sinai Medical Center
    • Panama City, Florida, United States, 32405
      • Gulf Coast Cancer Treatment Center
    • Tampa, Florida, United States, 33612
      • H. Lee Moffitt Cancer Center and Research Institute at University of South Florida
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University Hospital - Atlanta
    • Atlanta, Georgia, United States, 30303
      • Georgia Cancer Center for Excellence at Grady Memorial Hospital
    • Columbus, Georgia, United States, 31904
      • John B. Amos Community Cancer Center
    • Gainesville, Georgia, United States, 30501
      • Northeast Georgia Medical Center
    • Savannah, Georgia, United States, 31403
      • Curtis & Elizabeth Anderson Cancer Institute at Memorial Health University Medical Center
  • Idaho
    • Boise, Idaho, United States, 83706
      • Saint Alphonsus Cancer Care Center at Saint Alphonsus Regional Medical Center
  • Illinois
    • Arlington Heights, Illinois, United States, 60005
      • Northwest Community Hospital
    • Chicago, Illinois, United States, 60608
      • Mount Sinai Hospital Medical Center
    • Chicago, Illinois, United States, 60611
      • Robert H. Lurie Comprehensive Cancer Center at Northwestern University
    • Chicago, Illinois, United States, 60657
      • Creticos Cancer Center at Advocate Illinois Masonic Medical Center
    • Downers Grove, Illinois, United States, 60515
      • Cancer Care Center at Advocate Good Samaritan Hospital
    • Elk Grove Village, Illinois, United States, 60007
      • Alexian Brothers Cancer Care Center
    • Harvey, Illinois, United States, 60426
      • Ingalls Cancer Care Center at Ingalls Memorial Hospital
  • Indiana
    • Anderson, Indiana, United States, 46016
      • St. John's Cancer Center at St. John's Medical Center
    • Beech Grove, Indiana, United States, 46107
      • St. Francis Hospital and Health Centers
    • Elkhart, Indiana, United States, 46515
      • Elkhart General Hospital
    • Indianapolis, Indiana, United States, 46202
      • Indiana University Cancer Center
    • La Porte, Indiana, United States, 46350
      • Center for Cancer Therapy at LaPorte Hospital and Health Services
    • Plymouth, Indiana, United States, 46544
      • Saint Joseph Regional Medical Center - Plymouth Campus
    • 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
    • Bowling Green, Kentucky, United States, 42101
      • Cancer Treatment Center at the Medical Center - Bowling Green
    • Lexington, Kentucky, United States, 40536
      • Markey Cancer Center at University of Kentucky Chandler Medical Center
    • Louisville, Kentucky, United States, 40202
      • James Graham Brown Cancer Center at University of Louisville
  • Louisiana
    • Baton Rouge, Louisiana, United States, 70806
      • Baton Rouge General Regional Cancer Center
    • Baton Rouge, Louisiana, United States, 70809
      • Mary Bird Perkins Cancer Center - Baton Rouge
    • New Orleans, Louisiana, United States, 70112
      • MBCCOP - LSU Health Sciences Center
    • New Orleans, Louisiana, United States, 70112
      • Cancer Center at Medical Center of Louisiana - New Orleans
    • New Orleans, Louisiana, United States, 70112
      • Tulane Cancer Center
    • New Orleans, Louisiana, United States, 70115
      • New Orleans Cancer Institute at Memorial Medical Center
  • Maryland
    • Annapolis, Maryland, United States, 21401
      • DeCesaris Cancer Institute at Anne Arundel Medical Center
    • Elkton, Maryland, United States, 21921
      • Union Hospital Cancer Center at Union Hospital
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital Cancer Center
    • Boston, Massachusetts, United States, 02118
      • Cancer Research Center at Boston Medical Center
    • Fall River, Massachusetts, United States, 02721
      • Hudner Oncology Center at Saint Anne's Hospital
    • Hyannis, Massachusetts, United States, 02601
      • Cape Cod Hospital
    • Quincy, Massachusetts, United States, 02169
      • South Suburban Oncology Center
  • Michigan
    • Ann Arbor, Michigan, United States, 48106-0995
      • St. Joseph Mercy Cancer Center at St. Joseph Mercy Hospital
    • Ann Arbor, Michigan, United States, 48100
      • CCOP - Michigan Cancer Research Consortium
    • Dearborn, Michigan, United States, 48123
      • Oakwood Cancer Center at Oakwood Hospital and Medical Center
    • Detroit, Michigan, United States, 48201-1379
      • Barbara Ann Karmanos Cancer Institute
    • Detroit, Michigan, United States, 48236
      • Van Elslander Cancer Center at St. John Hospital and Medical Center
    • Flint, Michigan, United States, 48502
      • Hurley Medical Center
    • Flint, Michigan, United States, 48532
      • Genesys Hurley Cancer Institute
    • Flint, Michigan, United States, 48532
      • Great Lakes Cancer Institute at McLaren Regional Medical Center
    • Kalamazoo, Michigan, United States, 49007
      • West Michigan Cancer Center
    • Kalamazoo, Michigan, United States, 49007
      • Bronson Methodist Hospital
    • Kalamazoo, Michigan, United States, 49001
      • Borgess Medical Center
    • Kalamazoo, Michigan, United States, 49001
      • CCOP - Kalamazoo
    • Saginaw, Michigan, United States, 48601
      • Seton Cancer Institute - Saginaw
    • Warren, Michigan, United States, 48903
      • St. John Macomb Hospital
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic Cancer Center
  • Missouri
    • Cape Girardeau, Missouri, United States, 63703
      • Cancer Institute of Cape Girardeau
    • Columbia, Missouri, United States, 65203
      • Ellis Fischel Cancer Center at University of Missouri - Columbia
    • Kansas City, Missouri, United States, 64131
      • CCOP - Kansas City
    • Saint Louis, Missouri, United States, 63110
      • Saint Louis University Cancer Center
    • Saint Louis, Missouri, United States, 63110
      • Siteman Cancer Center at Barnes-Jewish Hospital
    • Springfield, Missouri, United States, 65802
      • CCOP - Cancer Research for the Ozarks
    • 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
    • Omaha, Nebraska, United States, 68114
      • Methodist Hospital Cancer Center at Nebraska Methodist Hospital - Omaha
  • Nevada
    • Las Vegas, Nevada, United States, 89106
      • CCOP - Southern Nevada Cancer Research Foundation
    • Las Vegas, Nevada, United States, 89102
      • University Medical Center of Southern Nevada
    • Reno, Nevada, United States, 89502
      • Washoe Cancer Services at Washoe Medical Center - Reno
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03756
      • Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center
  • New Jersey
    • Camden, New Jersey, United States, 08103
      • Cancer Institute of New Jersey at the Cooper University Hospital
    • Long Branch, New Jersey, United States, 07740
      • Monmouth Medical Center
    • Millville, New Jersey, United States, 08332
      • South Jersey Healthcare Regional Cancer Center
    • Mount Holly, New Jersey, United States, 08060
      • Fox Chase Virtua Health Cancer Program - Marlton
    • Toms River, New Jersey, United States, 08755
      • Community Medical Center
  • New York
    • Brooklyn, New York, United States, 11215
      • New York Methodist Hospital
    • Buffalo, New York, United States, 14263
      • Roswell Park Cancer Institute
    • Manhasset, New York, United States, 11030
      • CCOP - North Shore University Hospital
    • Plattsburgh, New York, United States, 12901
      • Fitzpatrick Cancer Center at Champlain Valley Physicians Hospital Medical Center
    • Syracuse, New York, United States, 13210
      • SUNY Upstate Medical University Hospital
  • North Carolina
    • Asheboro, North Carolina, United States, 27203
      • Randolph Hospital
    • Eden, North Carolina, United States, 27288
      • John Smith, Jr./Dalton McMichael Cancer Center at Morehead Memorial Hospital
    • Goldsboro, North Carolina, United States, 27534
      • Wayne Radiation Oncology
    • Goldsboro, North Carolina, United States, 27534
      • Wayne Memorial Hospital, Incorporated
    • Greensboro, North Carolina, United States, 27401
      • Moses Cone Regional Cancer Center at Wesley Long Community Hospital
    • Reidsville, North Carolina, United States, 27320
      • Annie Penn Cancer Center
    • Rutherfordton, North Carolina, United States, 28139
      • Rutherford Hospital
    • Wilson, North Carolina, United States, 27893
      • Wilson Medical Center
    • Winston-Salem, North Carolina, United States, 27157
      • Comprehensive Cancer Center at Wake Forest University
  • North Dakota
    • Minot, North Dakota, United States, 58701
      • Trinity Cancer Care Center
  • Ohio
    • Akron, Ohio, United States, 44307
      • McDowell Cancer Center at Akron General Medical Center
    • Akron, Ohio, United States, 44304
      • Akron City Hospital at Summa Health System
    • Canton, Ohio, United States, 44710-1799
      • Aultman Hospital Cancer Center at Aultman Health Foundation
    • Dayton, Ohio, United States, 45428
      • Veterans Affairs Medical Center - Dayton
    • Dayton, Ohio, United States, 45409
      • Miami Valley Hospital
    • Dayton, Ohio, United States, 45405
      • Grandview Hospital
    • Dayton, Ohio, United States, 45406
      • Good Samaritan Hospital
    • Dayton, Ohio, United States, 45415
      • Samaritan North Cancer Care Center
    • Dayton, Ohio, United States, 45429
      • CCOP - Dayton
    • Kettering, Ohio, United States, 45429
      • Charles F. Kettering Memorial Hospital
    • Lima, Ohio, United States, 45801
      • St. Rita's Medical Center
    • Middletown, Ohio, United States, 45044
      • Middletown Regional Hospital
    • Salem, Ohio, United States, 44460
      • Cancer Research UK Medical Oncology Unit at Churchill Hospital & Weatherall Institute of Molecular Medicine - Oxford
    • Troy, Ohio, United States, 45373
      • UVMC Cancer Care Center at Upper Valley Medical Center
    • Wooster, Ohio, United States, 44691
      • Cancer Treatment Center
    • Xenia, Ohio, United States, 45385
      • Ruth G. McMillan Cancer Center at Greene Memorial Hospital
  • Oklahoma
    • Tulsa, Oklahoma, United States, 74136
      • Natalie Warren Bryant Cancer Center at St. Francis Hospital
    • Tulsa, Oklahoma, United States, 74104
      • LaFortune Cancer Center at St. John Health System
  • Pennsylvania
    • Abington, Pennsylvania, United States, 19001
      • Abington Memorial Hospital
    • Bryn Mawr, Pennsylvania, United States, 19010
      • Bryn Mawr Hospital
    • Hershey, Pennsylvania, United States, 17033-0850
      • Penn State Cancer Institute at Milton S. Hershey Medical Center
    • Paoli, Pennsylvania, United States, 19301
      • Cancer Center at Paoli Memorial Hospital
    • Philadelphia, Pennsylvania, United States, 19111-2497
      • Fox Chase Cancer Center
    • Philadelphia, Pennsylvania, United States, 19141
      • Albert Einstein Cancer Center
    • Philadelphia, Pennsylvania, United States, 19107
      • Kimmel Cancer Center at Thomas Jefferson University - Philadelphia
    • Pittsburgh, Pennsylvania, United States, 15219
      • Mercy Hospital of Pittsburgh
    • Scranton, Pennsylvania, United States, 18501
      • Mercy Hospital Cancer Center - Scranton
    • Wynnewood, Pennsylvania, United States, 19096
      • CCOP - MainLine Health
    • Wynnewood, Pennsylvania, United States, 19096
      • Lankenau Cancer Center at Lankenau Hospital
  • South Carolina
    • Anderson, South Carolina, United States, 29621
      • Rose Ramer Cancer Clinic at Anderson Area Medical Center
    • Greenville, South Carolina, United States, 29615
      • CCOP - Greenville
    • Greenville, South Carolina, United States, 29601
      • Bon Secours St. Francis Health System
    • Greenville, South Carolina, United States, 29605
      • Greenville Hospital System Cancer Center
    • Spartanburg, South Carolina, United States, 29303
      • Gibbs Regional Cancer Center at Spartanburg Regional Medical Center
    • Spartanburg, South Carolina, United States, 29304
      • CCOP - Upstate Carolina
  • South Dakota
    • Rapid City, South Dakota, United States, 57701
      • Rapid City Regional Hospital
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt-Ingram Cancer Center at Vanderbilt Medical Center
  • Texas
    • Amarillo, Texas, United States, 79106
      • Harrington Cancer Center
    • Fort Sam Houston, Texas, United States, 78234
      • Brooke Army Medical Center
    • Houston, Texas, United States, 77030
      • M.D. Anderson Cancer Center at University of Texas
    • Lackland Air Force Base, Texas, United States, 78236
      • Wilford Hall Medical Center
  • Utah
    • Murray, Utah, United States, 84107
      • Cottonwood Hospital Medical Center
    • Ogden, Utah, United States, 84403
      • McKay-Dee Hospital Center
    • Provo, Utah, United States, 84603
      • Utah Valley Regional Medical Center - Provo
    • Saint George, Utah, United States, 84770
      • Dixie Regional Medical Center
    • Salt Lake City, Utah, United States, 84143
      • LDS Hospital
    • 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
  • Vermont
    • Burlington, Vermont, United States, 05401
      • Fletcher Allen Health Care - University Health Center Campus
  • Virginia
    • Danville, Virginia, United States, 24541
      • Danville Regional Medical Center
    • Kilmarnock, Virginia, United States, 22482
      • Rappahannock General Hospital
    • Portsmouth, Virginia, United States, 23708-2197
      • Naval Medical Center - Portsmouth
    • Richmond, Virginia, United States, 23249
      • Veterans Affairs Medical Center - Richmond
    • Richmond, Virginia, United States, 23298-0037
      • Massey Cancer Center at Virginia Commonwealth University
    • South Hill, Virginia, United States, 23970-0090
      • Community Memorial Health Center
  • Washington
    • Yakima, Washington, United States, 98902
      • North Star Lodge Cancer Center
    • Yakima, Washington, United States, 98902
      • Washington Hematology - Oncology Specialists
  • West Virginia
    • Wheeling, West Virginia, United States, 26003
      • Schiffler Cancer Center at Wheeling Hospital
  • Wisconsin
    • Green Bay, Wisconsin, United States, 54303
      • Green Bay Oncology, Limited at St. Mary's Hospital
    • Green Bay, Wisconsin, United States, 54301-3526
      • Green Bay Oncology, Limited at St. Vincent Hospital
    • Green Bay, Wisconsin, United States, 54301
      • St. Vincent Hospital
    • Green Bay, Wisconsin, United States, 54303
      • St. Mary's Hospital Medical Center
    • La Crosse, Wisconsin, United States, 54601
      • Gundersen Lutheran Cancer Center at Gundersen Lutheran Medical Center
    • Madison, Wisconsin, United States, 53792
      • University of Wisconsin Comprehensive Cancer Center
    • Manitowoc, Wisconsin, United States, 54221
      • Holy Family Memorial Medical Center
    • Marinette, Wisconsin, United States, 54143
      • Bay Area Cancer Care Center at Bay Area Medical Center
    • Menomonee Falls, Wisconsin, United States, 53051
      • Community Memorial Hospital
    • Milwaukee, Wisconsin, United States, 53295
      • Veterans Affairs Medical Center - Milwaukee (Zablocki)
    • Milwaukee, Wisconsin, United States, 53226
      • Medical College of Wisconsin Cancer Center
    • Milwaukee, Wisconsin, United States, 53211
      • St. Mary's Cancer Center at Columbia St. Mary's Hospital - Milwaukee Campus
    • Oconomowoc, Wisconsin, United States, 53066-3896
      • Oconomowoc Memorial Hospital
    • Racine, Wisconsin, United States, 53405
      • All Saints Cancer Center at All Saints Healthcare
    • Waukesha, Wisconsin, United States, 53188
      • Waukesha Memorial Hospital 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 of the oral cavity, oropharynx, hypopharynx, or larynx

  • Stage III or IV (T2, N2-3, M0 or T3-4, any N, M0)
• No metastases below the clavicle or more distant by clinical exam or radiology

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• Zubrod 0-1

Life expectancy

• Not specified

Hematopoietic

• Absolute granulocyte count at least 2,000/mm^3
• Platelet count at least 100,000/mm^3

Hepatic

• Bilirubin no greater than 1.5 mg/dL
• Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) no greater than 2 times upper limit of normal

Renal

• Creatinine no greater than 1.5 mg/dL
• Creatinine clearance at least 50 mL/min
• Calcium normal

Cardiovascular

• No symptomatic coronary artery disease (angina)
• No myocardial infarction within the past 6 months

Other

• No other invasive malignancy within the past 3 years except nonmelanoma skin cancer
• No simultaneous primary tumors
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Not specified

Chemotherapy

• No prior chemotherapy

Endocrine therapy

• Not specified

Radiotherapy

• No prior radiotherapy to the head and neck except radioactive iodine therapy

Surgery

• No prior surgery to the primary tumor or nodes except diagnostic biopsy or nodal sampling of neck disease

  • No radical or modified neck dissection

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
Other: Standard fractionation RT + cisplatin; Standard fractionation radiation therapy with concurrent cisplatin followed by conventional surgery for select patients.	Drug: cisplatin; 100 mg/m^2 intravenously on days 1, 22; Radiation: Standard fractionation RT; Radiation will be delivered in 2 Gy per fraction, five fractions a week. The primary tumor and clinically/radiologically involved nodes will receive 70 Gy in 7 weeks and uninvolved nodes will receive 50 Gy in 5 weeks. The anterior lower neck field will be treated with 2 Gy per fraction at 3-cm depth to a total dose of 50 Gy.; Procedure: Conventional surgery for select patients; Surgical removal (salvage resection) of the primary tumor should be performed if biopsy-proven cancer remains more than three months after completion of therapy. The nature of the surgical resection should be dictated by the extent of tumor at the initial evaluation. The operation should be conducted using accepted criteria for primary surgical treatment of the cancer. A planned neck dissection for patients with multiple neck nodes or with lymph nodes exceeding 3 cm in diameter (N2a, N2b, N3) is mandatory, regardless of the clinical and/or radiographic response. A neck dissection is required for patients with N1 disease if a palpable or worrisome radiographic abnormality persists in the neck six weeks after completion of therapy. Surgery should be performed within 2 weeks once the decision for neck dissection is made.
Experimental: Accelerated fractionation RT + cisplatin; Accelerated fractionation radiation therapy by concomitant boost with concurrent cisplatin followed by conventional surgery for select patients.	Drug: cisplatin; 100 mg/m^2 intravenously on days 1, 22; Procedure: Conventional surgery for select patients; Surgical removal (salvage resection) of the primary tumor should be performed if biopsy-proven cancer remains more than three months after completion of therapy. The nature of the surgical resection should be dictated by the extent of tumor at the initial evaluation. The operation should be conducted using accepted criteria for primary surgical treatment of the cancer. A planned neck dissection for patients with multiple neck nodes or with lymph nodes exceeding 3 cm in diameter (N2a, N2b, N3) is mandatory, regardless of the clinical and/or radiographic response. A neck dissection is required for patients with N1 disease if a palpable or worrisome radiographic abnormality persists in the neck six weeks after completion of therapy. Surgery should be performed within 2 weeks once the decision for neck dissection is made.; Radiation: Accelerated fractionation radiation therapy; Radiation to the initial target volume encompassing the gross and subclinical disease sites will be delivered in 1.8 Gy per fraction, five fractions a week to 54 Gy in 30 fractions over 6 weeks. At 32.4 Gy/18 Fx (i.e., latter part of week 4), the boost volume covering gross tumor and clinically/radiologically involved nodes will receive boost irradiation of 1.5 Gy/Fx as second daily fraction (at least 6 h interval) for a total of 12 treatment days (18 Gy total). The primary tumor and clinically/radiologically involved nodes will receive 72 Gy in 42 fractions over 6 weeks and uninvolved nodes will receive 54 Gy in 6 weeks. Clinically/radiologically negative posterior neck should receive a minimum dose of 50.4 Gy at 3 cm. The anterior lower neck field will be treated with 1.8 Gy per fraction at 3-cm depth to a total dose of 50.4 Gy in 28 fractions in 5.6 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (Percentage of Participants Alive)	Overall survival time is defined as time from randomization to the date of death (failure) or last known follow-up (censored). Overall survival rates are estimated by the Kaplan-Meier method. The full distribution is the outcome of interest, and the protocol specifies that the distributions of failure times be compared between the arms, which is reported in the statistical analysis results. Three-year estimates are provided as a summary of the distributions. Analysis was planned to occur after 309 deaths had been reported.	From randomization to last follow-up. Follow-up schedule from end of treatment: 6-8 weeks, every 3 mo. for 2 yr., then every 6 mo. for 3 yr., then yearly. Maximum follow-up at time of analysis was 6.5 years. Three-year rates are reported here.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Correlation of Epidermal Growth Factor Receptor(EGFR) With Outcomes		From randomization to date of death or last follow-up
Correlation of COX-2 With Outcomes		From randomization to date of death or last follow-up
Local-regional Failure (Percentage of Participants With Local-regional Failure)	Local-regional failure time is defined as time from randomization to persistent disease in the primary tumor or regional nodes (considered an event at day 1), relapse/progression in either of those sites (considered an event at the time of relapse/progression), death (competing event), or last follow-up (censored). Progression is defined as an estimated increase in the size of the tumor of greater than 25% or appearance of new areas of malignant disease. The full distribution is the outcome of interest, and the protocol specifies that the distributions of failure times be compared between the arms, which is reported in the statistical analysis results. Three-year estimates are provided as a summary of the distributions. Analysis was planned to occur after 309 deaths had been reported.	From randomization to last follow-up. Follow-up schedule from end of treatment: 6-8 weeks, every 3 mo. for 2 yr., then every 6 mo. for 3 yr., then yearly. Maximum follow-up at time of analysis was 6.5 years. Three-year rates are reported here.
Local-regional Failure (Alternate Definition) [Percentage of Participants With Local-regional Failure]	Local-regional failure time is defined as time from randomization to relapse/progression in the primary tumor or regional nodes (event), death due to study cancer or unknown causes (event), death due to other causes (competing event), distant metastasis (competing event), or last follow-up (censored). Progression is defined as an estimated increase in the size of the tumor of greater than 25% or appearance of new areas of malignant disease. The full distribution is the outcome of interest, and the protocol specifies that the distributions of failure times be compared between the arms, which is reported in the statistical analysis results. Three-year estimates are provided as a summary of the distributions. Analysis was planned to occur after 309 deaths had been reported.	From randomization to last follow-up. Follow-up schedule from end of treatment: 6-8 weeks, every 3 mo. for 2 yr., then every 6 mo. for 3 yr., then yearly. Maximum follow-up at time of analysis was 6.5 years. Three-year rates are reported here.
Disease-free Survival (Percentage of Participants Alive Without Disease)	Disease-free survival time is defined as time from randomization to persistent disease in the primary tumor or regional nodes (considered an event at day 1), relapse/progression in either of those sites (considered an event at the time of relapse/progression), distant metastasis (event), second primary tumor (event), death (event), or last follow-up (censored). Progression is defined as an estimated increase in the size of the tumor of greater than 25% or appearance of new areas of malignant disease. The full distribution is the outcome of interest, and the protocol specifies that the distributions of failure times be compared between the arms, which is reported in the statistical analysis results. Three-year estimates are provided as a summary of the distributions. Analysis was planned to occur after 309 deaths had been reported.	From randomization to last follow-up. Follow-up schedule from end of treatment: 6-8 weeks, every 3 mo. for 2 yr., then every 6 mo. for 3 yr., then yearly. Maximum follow-up at time of analysis was 6.5 years. Three-year rates are reported here.
Progression-free Survival (Alternate Definition of Disease-free Survival) [Percentage of Participants Alive Without Progression]	Progression-free survival time is defined as time from randomization to relapse/progression in the primary site or regional nodes (event), distant metastasis (event), death (event), or last follow-up (censored). Progression is defined as an estimated increase in the size of the tumor of greater than 25% or appearance of new areas of malignant disease. The full distribution is the outcome of interest, and the protocol specifies that the distributions of failure times be compared between the arms, which is reported in the statistical analysis results. Three-year estimates are provided as a summary of the distributions. Analysis was planned to occur after 309 deaths had been reported.	From randomization to last follow-up. Follow-up schedule from end of treatment: 6-8 weeks, every 3 mo. for 2 yr., then every 6 mo. for 3 yr., then yearly. Maximum follow-up at time of analysis was 6.5 years. Three-year rates are reported here.
Percentage of Participants With Toxicity Grade 3 or Higher	Acute radiation therapy toxicities (within 90 days from start of radiation therapy) and systemic effects at any time were scored using Common Toxicity Criteria (CTC) version 2.0. Late RT toxicities (> 90 days from start of radiation therapy) were scored by the Radiation Therapy Oncology Group (RTOG)/European Organisation for. Research and Treatment of Cancer (EORTC) criteria. Both criteria grades toxicity severity from 1=mild to 5=death. Summary data is provided in this outcome measure; see Adverse Events Module for specific adverse event/toxicity data.	From randomization to last follow-up. Follow-up schedule from end of treatment: 6-8 weeks, every 3 mo. for 2 yr., then every 6 mo. for 3 yr., then yearly. Maximum follow-up at time of analysis was 6.5 years.
Performance Status Scale for Head and Neck Cancer (PSS-HN) Normalcy of Diet Score - Area Under the Curve (AUC) at One Year	The PSS-HN is a clinician-rated evaluation conducted as an unstructured interview format that assesses three functions: Normalcy of Diet (this outcome measure), Public Eating, and Understandability of Speech. Each function is scored from 0 to 100 and analyzed separately. Higher scores indicate better performance status. Treatment effect was analyzed as time-weighted average between baseline (pre-treatment) and one year calculated by use of area under the curve (AUC).	Baseline (pretreatment), sometime during the last two weeks of treatment, three months from start of treatment, and one year from start of treatment.
PSS-HN Public Eating Score - AUC at One Year	The Performance Status Scale for Head and Neck Cancer (PSS-HN) is a clinician-rated evaluation conducted as an unstructured interview format that assesses three functions: Normalcy of Diet , Public Eating (this outcome measure), and Understandability of Speech. Each function is scored from 0 to 100 and analyzed separately. Higher scores indicate better performance status. Treatment effect was analyzed as time-weighted average between baseline (pretreatment) and one year calculated by use of area under the curve (AUC).	Baseline (pretreatment), sometime during the last two weeks of treatment, three months from start of treatment, and one year from start of treatment.
PSS-HN Understandability of Speech Score - AUC at One Year	The Performance Status Scale for Head and Neck Cancer (PSS-HN) is a clinician-rated evaluation conducted as an unstructured interview format that assesses three functions: Normalcy of Diet , Public Eating, and Understandability of Speech (this outcome measure). Each function is scored from 0 to 100 and analyzed separately. Higher scores indicate better performance status. Treatment effect was analyzed as time-weighted average between baseline (pretreatment) and one year calculated by use of area under the curve (AUC).	Baseline (pretreatment), sometime during the last two weeks of treatment, three months from start of treatment, and one year from start of treatment.
Head and Neck Radiotherapy Questionnaire (HNRQ) - AUC at One Year	The HNRQ is a patient-reported questionnaire administrated through a paper format; it measures radiation-related side effects and the overall well-being of head and neck cancer patients in the past week. The overall score is the mean of the 22 questions, with a range of 1 to 7. Higher scores indicate better quality of life. Treatment effect was analyzed as time-weighted average between baseline (pre-treatment) and 1 year calculated by use of area under the curve (AUC).	Baseline (pretreatment), sometime during the last two weeks of treatment, three months from start of treatment, and one year from start of treatment.

Collaborators and Investigators

• Sponsor: Radiation Therapy Oncology Group
• Collaborators: National Cancer Institute (NCI); NRG Oncology
• Investigators: Principal Investigator: Phuc Felix Nguyen-Tan, MD, Chum Hospital Notre Dame

Publications and helpful links

General Publications

• Gillison ML, Zhang Q, Jordan R, Xiao W, Westra WH, Trotti A, Spencer S, Harris J, Chung CH, Ang KK. Tobacco smoking and increased risk of death and progression for patients with p16-positive and p16-negative oropharyngeal cancer. J Clin Oncol. 2012 Jun 10;30(17):2102-11. doi: 10.1200/JCO.2011.38.4099. Epub 2012 May 7.
• Wuthrick EJ, Zhang Q, Machtay M, et al.: The influence of institutional head and neck cancer (HNC) clinical trial accrual on overall survival (OS): An analysis of RTOG 0129. [Abstract] J Clin Oncol 30 (Suppl 15): A-5530, 2012.
• Ang KK, Harris J, Wheeler R, Weber R, Rosenthal DI, Nguyen-Tan PF, Westra WH, Chung CH, Jordan RC, Lu C, Kim H, Axelrod R, Silverman CC, Redmond KP, Gillison ML. Human papillomavirus and survival of patients with oropharyngeal cancer. N Engl J Med. 2010 Jul 1;363(1):24-35. doi: 10.1056/NEJMoa0912217. Epub 2010 Jun 7.
• Ang K, Zhang Q, Wheeler RH, et al.: A phase III trial (RTOG 0129) of two radiation-cisplatin regimens for head and neck carcinomas (HNC): impact of radiation and cisplatin intensity on outcome. [Abstract] J Clin Oncol 28 (Suppl 15): A-5507, 2010.
• Gillison ML, Harris J, Westra W, et al.: Survival outcomes by tumor human papillomavirus (HPV) status in stage III-IV oropharyngeal cancer (OPC) in RTOG 0129. [Abstract] J Clin Oncol 27 (Suppl 15): A-6003, 2009.
• Ang K, Pajak T, Rosenthal DI, et al.: A phase III trial to compare standard versus accelerated fractionation in combination with concurrent cisplatin for head and neck carcinomas (RTOG 0129): report of compliance and toxicity. [Abstract] Int J Radiat Oncol Biol Phys 69 (3 Suppl): A-21, S12-13, 2007.
• Mell LK, Shen H, Nguyen-Tan PF, Rosenthal DI, Zakeri K, Vitzthum LK, Frank SJ, Schiff PB, Trotti AM 3rd, Bonner JA, Jones CU, Yom SS, Thorstad WL, Wong SJ, Shenouda G, Ridge JA, Zhang QE, Le QT. Nomogram to Predict the Benefit of Intensive Treatment for Locoregionally Advanced Head and Neck Cancer. Clin Cancer Res. 2019 Dec 1;25(23):7078-7088. doi: 10.1158/1078-0432.CCR-19-1832. Epub 2019 Aug 16.
• Beitler JJ, Switchenko JM, Dignam JJ, McDonald MW, Saba NF, Shin DM, Magliocca KR, Cassidy RJ, El-Deiry MW, Patel MR, Steuer CE, Xiao C, Hudgins PA, Aiken AH, Curran WJ Jr, Le QT. Smoking, age, nodal disease, T stage, p16 status, and risk of distant metastases in patients with squamous cell cancer of the oropharynx. Cancer. 2019 Mar 1;125(5):704-711. doi: 10.1002/cncr.31820. Epub 2018 Dec 11.
• Wuthrick EJ, Zhang Q, Machtay M, Rosenthal DI, Nguyen-Tan PF, Fortin A, Silverman CL, Raben A, Kim HE, Horwitz EM, Read NE, Harris J, Wu Q, Le QT, Gillison ML. Institutional clinical trial accrual volume and survival of patients with head and neck cancer. J Clin Oncol. 2015 Jan 10;33(2):156-64. doi: 10.1200/JCO.2014.56.5218. Epub 2014 Dec 8.
• Nguyen-Tan PF, Zhang Q, Ang KK, Weber RS, Rosenthal DI, Soulieres D, Kim H, Silverman C, Raben A, Galloway TJ, Fortin A, Gore E, Westra WH, Chung CH, Jordan RC, Gillison ML, List M, Le QT. Randomized phase III trial to test accelerated versus standard fractionation in combination with concurrent cisplatin for head and neck carcinomas in the Radiation Therapy Oncology Group 0129 trial: long-term report of efficacy and toxicity. J Clin Oncol. 2014 Dec 1;32(34):3858-66. doi: 10.1200/JCO.2014.55.3925. Epub 2014 Nov 3.

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2002
• Primary Completion (Actual): June 1, 2010
• Study Completion (Actual): May 20, 2022

Study Registration Dates

• First Submitted: October 3, 2002
• First Submitted That Met QC Criteria: January 26, 2003
• First Posted (Estimated): January 27, 2003

Study Record Updates

• Last Update Posted (Actual): July 7, 2023
• Last Update Submitted That Met QC Criteria: July 3, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Keywords: stage III squamous cell carcinoma of the lip and oral cavity; stage IV squamous cell carcinoma of the lip and 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 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; Neoplasms by Site; Head and Neck Neoplasms; Antineoplastic Agents; Cisplatin
• Other Study ID Numbers: RTOG 0129; CDR0000257233; RTOG-H-0129

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO