Reduced-Dose Intensity-Modulated Radiation Therapy With or Without Cisplatin in Treating Patients With Advanced Oropharyngeal Cancer

A Randomized Phase II Trial for Patients With p16 Positive, Non-Smoking Associated, Locoregionally Advanced Oropharyngeal Cancer

This randomized phase II trial studies the side effects and how well modestly reduced-dose intensity-modulated radiation therapy (IMRT) with or without cisplatin works in treating patients with oropharyngeal cancer that has spread to other places in the body (advanced). Radiation therapy uses high energy x rays to kill tumor cells. Drugs used in chemotherapy, such as cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. It is not yet known whether IMRT is more effective with or without cisplatin in treating patients with oropharyngeal cancer.

Study Overview

• Status: Active, not recruiting
• Conditions: Tongue Carcinoma; Stage IVA Oropharyngeal Squamous Cell Carcinoma; Stage IVB Oropharyngeal Squamous Cell Carcinoma; Stage IVC Oropharyngeal Squamous Cell Carcinoma; Stage III Oropharyngeal Squamous Cell Carcinoma
• Intervention / Treatment: Drug: Cisplatin; Radiation: IMRT 6 weeks; Radiation: IMRT 5 weeks

Detailed Description

PRIMARY OBJECTIVES:

-To select the arm(s) achieving a 2-year progression-free survival rate of >= 85% without unacceptable swallowing toxicity at 1 year.

SECONDARY OBJECTIVES:

• To determine patterns of failure (locoregional relapse versus distant) and survival -(overall and progression-free) at 6 months and 2 years.
• To determine acute toxicity profiles at the end of radiation therapy and at 1 and 6 months.
• To determine late toxicity profiles at 1 and 2 years.
• To determine patient-reported swallowing outcomes at 6 months and 1 and 2 years.
• To determine the predictive value of 12-14 week, post-treatment fludeoxyglucose F 18 (FDG)-positron emission tomography (PET)/computed tomography (CT) for locoregional control and progression free survival (PFS) at 2 years.
• To determine the predictive value of blood and tissue biomarkers for disease outcomes at 2 years.
• To determine swallowing recovery per videofluoroscopy imaging at 2 years.

After completion of study treatment, patients are followed at 1 and 3 months then every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.

• Study Type: Interventional
• Enrollment (Actual): 316
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 4N2
      • Tom Baker Cancer Centre
    • Edmonton, Alberta, Canada, T6G 1Z2
      • Cross Cancer Institute
  • British Columbia
    • Victoria, British Columbia, Canada, V8R 6V5
      • BCCA-Vancouver Island Cancer Centre
  • Ontario
    • Hamilton, Ontario, Canada, L8V 5C2
      • Juravinski Cancer Centre at Hamilton Health Sciences
    • Kingston, Ontario, Canada, K7L 2V7
      • Kingston Health Sciences Centre
    • Toronto, Ontario, Canada, M5G 2M9
      • University Health Network-Princess Margaret Hospital
    • Toronto, Ontario, Canada, M4N 3M5
      • Odette Cancer Centre- Sunnybrook Health Sciences Centre
    • Windsor, Ontario, Canada, N8W 2X3
      • Windsor Regional Cancer Centre
  • Quebec
    • Montreal, Quebec, Canada, H3T 1E2
      • Jewish General Hospital
    • Montreal, Quebec, Canada, H2L 4M1
      • CHUM - Hopital Notre-Dame
    • Montreal, Quebec, Canada, H2W 1S6
      • McGill University Department of Oncology
  • Saskatchewan
    • Regina, Saskatchewan, Canada, S4T 7T1
      • Allan Blair Cancer Centre
    • Saskatoon, Saskatchewan, Canada, S7N 4H4
      • Saskatoon Cancer Centre
• Ireland
  • Co Dublin
    • Dublin, Co Dublin, Ireland, 6
      • Saint Lukes Hospital
• Saudi Arabia
  • Riyadh, Saudi Arabia, 11211
    • King Faisal Specialist Hospital and Research Centre
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • University of Alabama at Birmingham Cancer Center
  • Arizona
    • Gilbert, Arizona, United States, 85234
      • Banner MD Anderson Cancer Center
    • Tucson, Arizona, United States, 85719
      • Banner University Medical Center - Tucson
  • California
    • Berkeley, California, United States, 94704
      • Alta Bates Summit Medical Center-Herrick Campus
    • Burlingame, California, United States, 94010
      • Mills-Peninsula Medical Center
    • Cameron Park, California, United States, 95682
      • Sutter Cancer Centers Radiation Oncology Services-Cameron Park
    • Duarte, California, United States, 91010
      • City of Hope Comprehensive Cancer Center
    • Greenbrae, California, United States, 94904
      • Marin General Hospital
    • La Jolla, California, United States, 92093
      • UC San Diego Moores Cancer Center
    • Los Angeles, California, United States, 90027
      • Kaiser Permanente Los Angeles Medical Center
    • Modesto, California, United States, 95355
      • Memorial Medical Center
    • Oakland, California, United States, 94611
      • Kaiser Permanente Oakland-Broadway
    • Orange, California, United States, 92868
      • UC Irvine Health/Chao Family Comprehensive Cancer Center
    • Palo Alto, California, United States, 94304
      • Stanford Cancer Institute Palo Alto
    • Palo Alto, California, United States, 94301
      • Palo Alto Medical Foundation Health Care
    • Rancho Cordova, California, United States, 95670
      • Kaiser Permanente-Rancho Cordova Cancer Center
    • Rohnert Park, California, United States, 94928
      • Rohnert Park Cancer Center
    • Roseville, California, United States, 95678
      • The Permanente Medical Group-Roseville Radiation Oncology
    • Roseville, California, United States, 95661
      • Sutter Cancer Centers Radiation Oncology Services-Roseville
    • Sacramento, California, United States, 95816
      • Sutter Medical Center Sacramento
    • Sacramento, California, United States, 95817
      • University of California Davis Comprehensive Cancer Center
    • Sacramento, California, United States, 95823
      • South Sacramento Cancer Center
    • Saint Helena, California, United States, 94574
      • Saint Helena Hospital
    • San Diego, California, United States, 92134
      • Naval Medical Center -San Diego
    • San Francisco, California, United States, 94115
      • UCSF Medical Center-Mount Zion
    • San Jose, California, United States, 95124
      • Stanford Cancer Center South Bay
    • Santa Clara, California, United States, 95051
      • Kaiser Permanente Medical Center - Santa Clara
    • South Pasadena, California, United States, 91030
      • City of Hope South Pasadena
    • South San Francisco, California, United States, 94080
      • Kaiser Permanente Cancer Treatment Center
    • Sunnyvale, California, United States, 94086
      • Palo Alto Medical Foundation-Sunnyvale
    • Truckee, California, United States, 96161
      • Gene Upshaw Memorial Tahoe Forest Cancer Center
    • Walnut Creek, California, United States, 94598
      • John Muir Medical Center-Walnut Creek
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Hospital
    • Boulder, Colorado, United States, 80304
      • Rocky Mountain Cancer Centers-Boulder
    • Colorado Springs, Colorado, United States, 80907
      • Penrose-Saint Francis Healthcare
    • Englewood, Colorado, United States, 80113
      • Swedish Medical Center
    • Fort Collins, Colorado, United States, 80524
      • Poudre Valley Hospital
    • Greeley, Colorado, United States, 80631
      • North Colorado Medical Center
    • Parker, Colorado, United States, 80138
      • Parker Adventist Hospital
  • Connecticut
    • New Haven, Connecticut, United States, 06520
      • Yale University
  • Delaware
    • Newark, Delaware, United States, 19718
      • Christiana Care Health System-Christiana Hospital
    • Rehoboth Beach, Delaware, United States, 19971
      • Beebe Health Campus
  • Florida
    • Hollywood, Florida, United States, 33021
      • Memorial Regional Hospital/Joe DiMaggio Children's Hospital
    • Miami, Florida, United States, 33136
      • University of Miami Miller School of Medicine-Sylvester Cancer Center
    • Miami, Florida, United States, 33176
      • Miami Cancer Institute
    • Pembroke Pines, Florida, United States, 33028
      • Memorial Hospital West
    • Tampa, Florida, United States, 33612
      • Moffitt Cancer Center
    • Weston, Florida, United States, 33331
      • Cleveland Clinic-Weston
  • Georgia
    • Atlanta, Georgia, United States, 30308
      • Emory University Hospital Midtown
    • Atlanta, Georgia, United States, 30322
      • Emory University Hospital/Winship Cancer Institute
    • Atlanta, Georgia, United States, 30342
      • Emory Saint Joseph's Hospital
    • Atlanta, Georgia, United States, 30303
      • Grady Health System
    • Atlanta, Georgia, United States, 30309
      • Piedmont Hospital
    • Savannah, Georgia, United States, 31405
      • Lewis Cancer and Research Pavilion at Saint Joseph's/Candler
  • Hawaii
    • Honolulu, Hawaii, United States, 96813
      • Queen's Medical Center
    • Honolulu, Hawaii, United States, 96817
      • The Cancer Center of Hawaii-Liliha
  • Idaho
    • Boise, Idaho, United States, 83706
      • Saint Alphonsus Cancer Care Center-Boise
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University
    • Chicago, Illinois, United States, 60612
      • John H Stroger Jr Hospital of Cook County
    • Decatur, Illinois, United States, 62526
      • Decatur Memorial Hospital
    • Evanston, Illinois, United States, 60201
      • NorthShore University HealthSystem-Evanston Hospital
    • Glenview, Illinois, United States, 60026
      • NorthShore University HealthSystem-Glenbrook Hospital
    • Highland Park, Illinois, United States, 60035
      • NorthShore University HealthSystem-Highland Park Hospital
    • Maywood, Illinois, United States, 60153
      • Loyola University Medical Center
  • Indiana
    • Fort Wayne, Indiana, United States, 46805
      • Parkview Hospital Randallia
    • Fort Wayne, Indiana, United States, 46804
      • Radiation Oncology Associates PC
    • South Bend, Indiana, United States, 46601
      • Memorial Hospital of South Bend
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • University of Kansas Cancer Center
    • Lawrence, Kansas, United States, 66044
      • Lawrence Memorial Hospital
    • Olathe, Kansas, United States, 66061
      • Olathe Medical Center
    • Overland Park, Kansas, United States, 66210
      • University of Kansas Cancer Center-Overland Park
    • Wichita, Kansas, United States, 67214
      • Ascension Via Christi Hospitals Wichita
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • The James Graham Brown Cancer Center at University of Louisville
    • Louisville, Kentucky, United States, 40245
      • Jewish Hospital Medical Center Northeast
  • Maryland
    • Baltimore, Maryland, United States, 21204
      • Greater Baltimore Medical Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02118
      • Boston Medical Center
    • Burlington, Massachusetts, United States, 01805
      • Lahey Hospital and Medical Center
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan Comprehensive Cancer Center
    • Ann Arbor, Michigan, United States, 48106
      • Saint Joseph Mercy Hospital
    • Brownstown, Michigan, United States, 48183
      • Henry Ford Cancer Institute-Downriver
    • Clinton Township, Michigan, United States, 48038
      • Henry Ford Macomb Hospital-Clinton Township
    • Detroit, Michigan, United States, 48202
      • Henry Ford Hospital
    • Grand Rapids, Michigan, United States, 49503
      • Mercy Health Saint Mary's
    • Livonia, Michigan, United States, 48154
      • Saint Mary Mercy Hospital
    • Muskegon, Michigan, United States, 49444
      • Mercy Health Mercy Campus
    • Saint Joseph, Michigan, United States, 49085
      • Lakeland Medical Center Saint Joseph
    • West Bloomfield, Michigan, United States, 48322
      • Henry Ford West Bloomfield Hospital
  • Minnesota
    • Coon Rapids, Minnesota, United States, 55433
      • Mercy Hospital
    • Saint Cloud, Minnesota, United States, 56303
      • Coborn Cancer Center at Saint Cloud Hospital
    • Saint Louis Park, Minnesota, United States, 55416
      • Park Nicollet Clinic - Saint Louis Park
    • Saint Paul, Minnesota, United States, 55101
      • Regions Hospital
    • Saint Paul, Minnesota, United States, 55102
      • United Hospital
    • Shakopee, Minnesota, United States, 55379
      • Saint Francis Regional Medical Center
  • Missouri
    • Creve Coeur, Missouri, United States, 63141
      • Siteman Cancer Center at West County Hospital
    • Kansas City, Missouri, United States, 64116
      • North Kansas City Hospital
    • Kansas City, Missouri, United States, 64131
      • The University of Kansas Cancer Center-South
    • Kansas City, Missouri, United States, 64154
      • The University of Kansas Cancer Center-North
    • Lee's Summit, Missouri, United States, 64064
      • The University of Kansas Cancer Center-Lee's Summit
    • Rolla, Missouri, United States, 65401
      • Delbert Day Cancer Institute at PCRMC
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine
    • Saint Louis, Missouri, United States, 63141
      • Mercy Hospital Saint Louis
    • Saint Peters, Missouri, United States, 63376
      • Siteman Cancer Center at Saint Peters Hospital
    • Springfield, Missouri, United States, 65807
      • CoxHealth South Hospital
    • Springfield, Missouri, United States, 65804
      • Mercy Hospital Springfield
  • Montana
    • Billings, Montana, United States, 59101
      • Billings Clinic Cancer Center
    • Great Falls, Montana, United States, 59405
      • Benefis Healthcare- Sletten Cancer Institute
    • Missoula, Montana, United States, 59804
      • Community Medical Hospital
  • Nebraska
    • Grand Island, Nebraska, United States, 68803
      • CHI Health Saint Francis
    • Omaha, Nebraska, United States, 68114
      • Nebraska Methodist Hospital
    • Omaha, Nebraska, United States, 68198
      • University of Nebraska Medical Center
    • Omaha, Nebraska, United States, 68124
      • Alegent Health Bergan Mercy Medical Center
    • Omaha, Nebraska, United States, 68130
      • Alegent Health Lakeside Hospital
  • Nevada
    • Las Vegas, Nevada, United States, 89106
      • Radiation Oncology Centers of Nevada Central
    • Reno, Nevada, United States, 89502
      • Renown Regional Medical Center
    • Reno, Nevada, United States, 89503
      • Saint Mary's Regional Medical Center
  • New Hampshire
    • Dover, New Hampshire, United States, 03820
      • Wentworth-Douglass Hospital
    • Lebanon, New Hampshire, United States, 03756
      • Dartmouth Hitchcock Medical Center
  • New Jersey
    • Basking Ridge, New Jersey, United States, 07920
      • Memorial Sloan Kettering Basking Ridge
    • Livingston, New Jersey, United States, 07039
      • Saint Barnabas Medical Center
    • Mount Holly, New Jersey, United States, 08060
      • Virtua Memorial
    • Voorhees, New Jersey, United States, 08043
      • Virtua Voorhees
  • New Mexico
    • Albuquerque, New Mexico, United States, 87102
      • University of New Mexico Cancer Center
  • New York
    • Commack, New York, United States, 11725
      • Memorial Sloan Kettering Commack
    • Harrison, New York, United States, 10604
      • Memorial Sloan Kettering Westchester
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering Cancer Center
    • Uniondale, New York, United States, 11553
      • Memorial Sloan Kettering Nassau
    • White Plains, New York, United States, 10601
      • Dickstein Cancer Treatment Center
  • North Carolina
    • Asheville, North Carolina, United States, 28801
      • Mission Hospital Inc-Memorial Campus
    • Kinston, North Carolina, United States, 28501
      • Vidant Oncology-Kinston
    • Supply, North Carolina, United States, 28462
      • NHRMC Radiation Oncology - Supply
    • Wilmington, North Carolina, United States, 28401
      • NHRMC Radiation Oncology - 16th Street
  • Ohio
    • Beachwood, Ohio, United States, 44122
      • UHHS-Chagrin Highlands Medical Center
    • Chardon, Ohio, United States, 44024
      • Geauga Hospital
    • Cincinnati, Ohio, United States, 45219
      • University of Cincinnati/Barrett Cancer Center
    • Cleveland, Ohio, United States, 44106
      • Case Western Reserve University
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Foundation
    • Cleveland, Ohio, United States, 44111
      • Cleveland Clinic Cancer Center/Fairview Hospital
    • Columbus, Ohio, United States, 43210
      • Ohio State University Comprehensive Cancer Center
    • Elyria, Ohio, United States, 44035
      • Mercy Cancer Center-Elyria
    • Independence, Ohio, United States, 44131
      • Cleveland Clinic Cancer Center Independence
    • Mayfield Heights, Ohio, United States, 44124
      • Hillcrest Hospital Cancer Center
    • Mentor, Ohio, United States, 44060
      • UH Seidman Cancer Center at Lake Health Mentor Campus
    • Middleburg Heights, Ohio, United States, 44130
      • UH Seidman Cancer Center at Southwest General Hospital
    • Parma, Ohio, United States, 44129
      • University Hospitals Parma Medical Center
    • Sandusky, Ohio, United States, 44870
      • North Coast Cancer Care
    • Sandusky, Ohio, United States, 44870
      • UH Seidman Cancer Center at Firelands Regional Medical Center
    • Strongsville, Ohio, United States, 44136
      • Cleveland Clinic Cancer Center Strongsville
    • Sylvania, Ohio, United States, 43560
      • ProMedica Flower Hospital
    • West Chester, Ohio, United States, 45069
      • University Pointe
    • Westlake, Ohio, United States, 44145
      • UHHS-Westlake Medical Center
    • Wooster, Ohio, United States, 44691
      • Cleveland Clinic Wooster Family Health and Surgery Center
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • University of Oklahoma Health Sciences Center
    • Oklahoma City, Oklahoma, United States, 73120
      • Mercy Hospital Oklahoma City
  • Oregon
    • Gresham, Oregon, United States, 97030
      • Legacy Mount Hood Medical Center
  • Pennsylvania
    • Abington, Pennsylvania, United States, 19001
      • Abington Memorial Hospital
    • Beaver, Pennsylvania, United States, 15009
      • UPMC-Heritage Valley Health System Beaver
    • Greensburg, Pennsylvania, United States, 15601
      • UPMC Cancer Centers - Arnold Palmer Pavilion
    • Hershey, Pennsylvania, United States, 17033-0850
      • Penn State Milton S Hershey Medical Center
    • Johnstown, Pennsylvania, United States, 15901
      • UPMC-Johnstown/John P. Murtha Regional Cancer Center
    • McKeesport, Pennsylvania, United States, 15132
      • UPMC Cancer Center at UPMC McKeesport
    • Moon, Pennsylvania, United States, 15108
      • UPMC-Coraopolis/Heritage Valley Radiation Oncology
    • Philadelphia, Pennsylvania, United States, 19111
      • Fox Chase Cancer Center
    • Pittsburgh, Pennsylvania, United States, 15232
      • UPMC-Shadyside Hospital
    • Pittsburgh, Pennsylvania, United States, 15215
      • UPMC-Saint Margaret
    • Pittsburgh, Pennsylvania, United States, 15237
      • UPMC-Passavant Hospital
    • Seneca, Pennsylvania, United States, 16346
      • UPMC Cancer Center at UPMC Northwest
    • Uniontown, Pennsylvania, United States, 15401
      • UPMC Uniontown Hospital Radiation Oncology
    • Washington, Pennsylvania, United States, 15301
      • UPMC Washington Hospital Radiation Oncology
    • West Reading, Pennsylvania, United States, 19611
      • Reading Hospital
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina
    • Greenville, South Carolina, United States, 29605
      • Greenville Health System Cancer Institute-Faris
    • Greenville, South Carolina, United States, 29615
      • Greenville Health System Cancer Institute-Eastside
    • Greer, South Carolina, United States, 29650
      • Greenville Health System Cancer Institute-Greer
    • Seneca, South Carolina, United States, 29672
      • Greenville Health System Cancer Institute-Seneca
    • Spartanburg, South Carolina, United States, 29303
      • Spartanburg Medical Center
    • Spartanburg, South Carolina, United States, 29307
      • Greenville Health System Cancer Institute-Spartanburg
  • Tennessee
    • Knoxville, Tennessee, United States, 37909
      • Tennessee Cancer Specialists-Dowell Springs
  • Texas
    • Galveston, Texas, United States, 77555-0565
      • University of Texas Medical Branch
    • Houston, Texas, United States, 77030
      • M D Anderson Cancer Center
    • Houston, Texas, United States, 77094
      • MD Anderson in Katy
    • League City, Texas, United States, 77573
      • UTMB Cancer Center at Victory Lakes
    • Nassau Bay, Texas, United States, 77058
      • MD Anderson League City
    • The Woodlands, Texas, United States, 77384
      • MD Anderson in The Woodlands
  • Utah
    • Murray, Utah, United States, 84107
      • Intermountain Medical Center
    • Ogden, Utah, United States, 84403
      • McKay-Dee Hospital Center
    • Salt Lake City, Utah, United States, 84112
      • Huntsman Cancer Institute/University of Utah
    • Salt Lake City, Utah, United States, 84106
      • Utah Cancer Specialists-Salt Lake City
  • Vermont
    • Saint Johnsbury, Vermont, United States, 05819
      • Norris Cotton Cancer Center-North
  • Virginia
    • Charlottesville, Virginia, United States, 22908
      • University of Virginia Cancer Center
    • Richmond, Virginia, United States, 23298
      • Virginia Commonwealth University/Massey Cancer Center
  • Washington
    • Gig Harbor, Washington, United States, 98332
      • Tacoma/Valley Radiation Oncology Centers-Gig Harbor
    • Seattle, Washington, United States, 98101
      • Virginia Mason Medical Center
    • Tacoma, Washington, United States, 98405
      • MultiCare Tacoma General Hospital
    • Tacoma, Washington, United States, 98405
      • Tacoma/Valley Radiation Oncology Centers-Saint Joe's
    • Tacoma, Washington, United States, 97405
      • Tacoma/Valley Radiation Oncology Centers-Jackson Hall
    • Vancouver, Washington, United States, 98686
      • Legacy Salmon Creek Hospital
  • Wisconsin
    • Green Bay, Wisconsin, United States, 54301
      • Saint Vincent Hospital Cancer Center Green Bay
    • Green Bay, Wisconsin, United States, 54303
      • Saint Vincent Hospital Cancer Center at Saint Mary's
    • Johnson Creek, Wisconsin, United States, 53038
      • UW Cancer Center Johnson Creek
    • La Crosse, Wisconsin, United States, 54601
      • Gundersen Lutheran Medical Center
    • Madison, Wisconsin, United States, 53792
      • University of Wisconsin Hospital and Clinics
    • Menomonee Falls, Wisconsin, United States, 53051
      • Community Memorial Hospital
    • Milwaukee, Wisconsin, United States, 53226
      • Medical College of Wisconsin
    • Racine, Wisconsin, United States, 53405
      • Ascension All Saints Hospital
    • Sheboygan, Wisconsin, United States, 53081
      • HSHS Saint Nicholas Hospital
    • West Bend, Wisconsin, United States, 53095
      • The Alyce and Elmore Kraemer Cancer Care Center
    • Wisconsin Rapids, Wisconsin, United States, 54494
      • Aspirus UW Cancer Center

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria

Step 1: Registration:

1. Pathologically (histologically or cytologically) proven diagnosis of squamous cell carcinoma (including the histological variants papillary squamous cell carcinoma and basaloid squamous cell carcinoma) of the oropharynx (tonsil, base of tongue, soft palate, or oropharyngeal walls); cytologic diagnosis from a cervical lymph node is sufficient in the presence of clinical evidence of a primary tumor in the oropharynx. Clinical evidence should be documented, may consist of palpation, imaging, or endoscopic evaluation, and should be sufficient to estimate the size of the primary (for T stage).
2. Patients must have clinically or radiographically evident measurable disease at the primary site or at nodal stations. Tonsillectomy or local excision of the primary without removal of nodal disease is permitted, as is excision removing gross nodal disease but with intact primary site. Limited neck dissections retrieving ≤ 4 nodes are permitted and considered as non-therapeutic nodal excisions.
3. Immunohistochemical staining for p16 must be performed on tissue, and this tissue must be submitted for central review. Fine needle aspiration (FNA) biopsy specimens may be used as the sole diagnostic tissue if formalin-fixed paraffin-embedded cell block material is available for p16 immunohistochemistry. FNA specimens prepared with adequate p16 testing in this manner are acceptable to submit for central review. If the p16 preparation is not adequate, additional specimens will be required to establish p16 status. Centers are encouraged to contact the pathology chairs for clarification.

4. Clinical stage T1-T2, N1-N2b or T3, N0-N2b (AJCC, 7th ed.) including no distant metastases based on the following diagnostic workup:

   • General history and physical examination within 56 days prior to registration;
   • Fiberoptic exam with laryngopharyngoscopy (mirror and/or fiberoptic and/or direct procedure) within 70 days prior to registration;

   • One of the following combinations of imaging is required within 56 days prior to registration:

     1. A computed tomography (CT) scan of the neck (with contrast) and a chest CT scan (with or without contrast);
     2. or an MRI of the neck (with contrast) and a chest CT scan (with or without contrast);
     3. or a CT scan of neck (with contrast) and a PET/CT of neck and chest (with or without contrast);
     4. or an MRI of the neck (with contrast) and a PET/CT of neck and chest (with or without contrast).

   Note: A CT scan of neck and/or a PET/CT performed for the purposes of radiation planning may serve as both staging and planning tools.

5. Patients must provide their personal smoking history prior to registration. The lifetime cumulative history cannot exceed 10 pack-years. The following formula is used to calculate the pack-years during the periods of smoking in the patient's life; the cumulative total of the number of pack-years during each period of active smoking is the lifetime cumulative history.

   Number of pack-years = [Frequency of smoking (number of cigarettes per day) × duration of cigarette smoking (years)] / 20

   Note: Twenty cigarettes is considered equivalent to one pack. The effect of non-cigarette tobacco products on the survival of patients with p16-positive oropharyngeal cancers is undefined. While there are reportedly increased risks of head and neck cancer associated with sustained heavy cigar and pipe use (Wyss 2013), such sustained use of non-cigarette products is unusual and does not appear to convey added risk with synchronous cigarette smoking. Cigar and pipe tobacco consumption is therefore not included in calculating the lifetime pack-years. Marijuana consumption is likewise not considered in this calculation. There is no clear scientific evidence regarding the role of chewing tobacco-containing products in this disease, although this is possibly more concerning given the proximity of the oral cavity and oropharynx. In any case, investigators are discouraged from enrolling patients with a history of very sustained use (such as several years or more) of non-cigarette tobacco products alone.

6. Zubrod Performance Status of 0-1 within 56 days prior to registration;
7. Age ≥ 18;
8. The trial is open to both genders;

9. Adequate hematologic function within 14 days prior to registration, defined as follows:

   • Absolute neutrophil count (ANC) ≥ 1,500 cells/mm3;
   • Platelets ≥ 100,000 cells/mm3;
   • Hemoglobin (Hgb) ≥ 8.0 g/dl; Note: The use of transfusion or other intervention to achieve Hgb ≥ 8.0 g/dl is acceptable.

10. Adequate renal function within 14 days prior to registration, defined as follows:

    • Serum creatinine (Cr) < 1.5 mg/dl or creatinine clearance (CC) ≥ 50 ml/min determined by 24-hour collection or estimated by Cockcroft-Gault formula:

    • CC male = [(140 - age) x (wt in kg)] / [(Serum Cr mg/dl) x (72)]
    • CC female = 0.85 x (CC male)

11. Adequate hepatic function within 14 days prior to registration defined as follows:

    • Bilirubin < 2 mg/dl;
    • Aspartate transaminase (AST) or alanine transaminase (ALT) < 3 x the upper limit of normal.
12. Negative serum pregnancy test within 14 days prior to registration for women of childbearing potential;
13. Patients who are HIV positive but have no prior Acquired Immune Deficiency Syndrome (AIDS) -defining illness and have CD4 cells of at least 350/mm3 are eligible. HIV-positive patients must not have multi-drug resistant HIV infection or other concurrent AIDS-defining conditions. Patients must not be sero-positive for Hepatitis B (Hepatitis B surface antigen positive or anti-hepatitis B core antigen positive) or sero-positive for Hepatitis C (anti-Hepatitis C antibody positive). However, patients who are immune to hepatitis B (anti-Hepatitis B surface antibody positive) are eligible (e.g. patients immunized against hepatitis B).
14. The patient must provide study-specific informed consent prior to study entry, including consent for mandatory submission of tissue for required, central p16 review.

15. Patients who speak English (or read one of the languages for which a translation is available (see Section 10.2) must consent to complete the mandatory dysphagia-related patient reported instrument (MDADI). If the patient cannot understand spoken English and reads only languages not available in the MDADI translations, the patient can still participate in the trial, as this has been factored into the trial statistics. For all other patients, the MDADI is mandatory as it is included in the primary endpoint to be studied.

    Step 2: Randomization:

16. p16 positive by immunohistochemistry (defined as greater than 70% strong nuclear or nuclear and cytoplasmic staining of tumor cells), confirmed by central pathology review; (see Section 10.1 for details).

Exclusion Criteria

Step 1: Registration:

1. Cancers considered to be from an oral cavity site (oral tongue, floor mouth, alveolar ridge, buccal or lip), or the nasopharynx, hypopharynx, or larynx, even if p16 positive, or histologies of adenosquamous, verrucous, or spindle cell carcinomas;
2. Carcinoma of the neck of unknown primary site origin (even if p16 positive);
3. Radiographically matted nodes, defined as 3 abutting nodes with loss of the intervening fat plane;
4. Supraclavicular nodes, defined as nodes visualized on the same axial imaging slice as the clavicle;
5. Definitive clinical or radiologic evidence of metastatic disease or adenopathy below the clavicles;
6. Gross total excision of both primary and nodal disease with curative intent; this includes tonsillectomy, local excision of primary site, and nodal excision that removes all clinically and radiographically evident disease. In other words, to participate in this protocol, the patient must have clinically or radiographically evident gross disease for which disease response can be assessed.
7. Patients with simultaneous primary cancers or separate bilateral primary tumor sites are excluded with the exception of patients with bilateral tonsil cancers;
8. Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for a minimum of 1095 days (3 years) (for example, carcinoma in situ of the breast, oral cavity, or cervix are all permissible);
9. Prior systemic chemotherapy for the study cancer; note that prior chemotherapy for a different cancer is allowable;
10. Prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields;

11. Severe, active co-morbidity defined as follows:

    • Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months;
    • Transmural myocardial infarction within the last 6 months;
    • Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration;
    • Chronic Obstructive Pulmonary Disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy within 30 days of registration;
    • Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects; note, however, that laboratory tests for liver function and coagulation parameters are not required for entry into this protocol other than those requested in Section 3.2.10.
    • Acquired Immune Deficiency Syndrome (AIDS) based upon current Centers for Disease Control and Prevention (CDC) definition with immune compromise greater than that noted in Inclusion Criterion 13; note, however, that HIV testing is not required for entry into this protocol. The need to exclude patients with AIDS from this protocol is necessary because the treatments involved in this protocol may be significantly immunosuppressive. Protocol-specific requirements may also exclude immuno-compromised patients.
12. Pregnancy; this exclusion is necessary because the treatment involved in this study may be significantly teratogenic.
13. Prior allergic reaction to cisplatin.

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: IMRT 6 weeks + cisplatin; IMRT 6 weeks with concurrent cisplatin	Drug: Cisplatin; 40 mg/m2 IV (intravenously) weekly for 6 weeks; Radiation: IMRT 6 weeks; Intensity-modulated radiation therapy (IMRT), 30 fractions over 6 weeks, 5 fractions per week, 2 Gray per fraction to total dose of 60 Gy; Other Names: Intensity-Modulated Radiotherapy
Experimental: IMRT 5 weeks	Radiation: IMRT 5 weeks; Intensity-modulated radiation therapy (IMRT), 30 fractions over 5 weeks, 6 fractions per week, 2 Gray per fraction to total dose of 60 Gy; Other Names: Intensity-Modulated Radiotherapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Alive Without Progression at Two Years (Progression-free Survival)	Progression is defined as local, regional, or distant disease progression or death due to any cause. Percentage is estimated using the binomial distribution.	From randomization to 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Local-regional Failure	Local-regional failure is defined as local or regional progression, salvage surgery of the primary tumor with tumor present/unknown, salvage neck dissection with tumor present/unknown > 20 weeks after the end of radiation therapy, death due to study cancer without documented progression, or death due to unknown causes without documented progression. Distant metastasis and death due to other causes are considered competing risks. Local-regional failure time is defined as time from randomization to the date of first progression/death or last known follow-up (censored). Rates are estimated by the cumulative incidence method.	From randomization to 2 years
Percentage of Participants With Distant Metastasis	Distant metastasis is defined as distant progression. Local-regional failure and death due to any cause are considered competing risks. Distant metastasis time is defined as time from randomization to the date of progression/death or last known follow-up (censored). Rates are estimated by the cumulative incidence method.	From randomization to 2 years
Percentage of Participants Alive	Overall survival time is defined as time from randomization to the date of death or last known follow-up (censored). Overall survival rates are estimated by the Kaplan-Meier method.	from randomization to 2 years
Percentage of Participants With Grade 3+ Adverse Events	Adverse events were graded using the Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Grade refers to the severity of the AE. The CTCAE v4.0 assigns Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1 Mild, Grade 2 Moderate, Grade 3 Severe, Grade 4 Life-threatening or disabling, Grade 5 Death related to AE.	End of radiation therapy (RT) (approximately 6 weeks for Arm 1 and 5 weeks for Arm 2), then 1 month, 6 months, 1 year, and two years after end of RT
Mean One-year Total MD Anderson Dysphagia Inventory (MDADI) Score (Patient-reported Swallowing Outcome)	The MDADI is a 20-item tool with each item scored as Strongly agree; Agree; No opinion; Disagree; or Strongly disagree. There is 1 global item (G1), 6 emotional subscale items (E2-E7), 5 functional subscale items (F1-F5), and 8 physical subscale items (P1-P8). For all items except E7 and F2, Strongly agree corresponds to a score of 1, Agree 2, No opinion 3, Disagree 4, and Strongly disagree 5. For E7 and F2, the scores are reversed; these 2 items are rescored to match the others before calculating summary scores. The composite (total) score is the mean of the 19 items (other than G1) X 20. Composite scores range from 20 to 100 with higher scores indicating less dysphagia.	One year post-RT. Radiation therapy (RT) ends at approximately 6 weeks for Arm 1 and 5 weeks for Arm 2
Negative Predictive Value (NPV) of Post-treatment FDG-PET/CT Scan [Fluorodeoxyglucose (FDG) Positron Emission Tomography (PET)/Computed Tomography (CT)] for Progression-free Survival and Local-regional Control at Two Years	NPV is the percentage of participants alive and failure-free at 2 years among those with a negative post-treatment scan, as evaluated by central review. Negative scan determined as follows: primary site, right neck, left neck evaluated using a 5-point ordinal scale: 1-Definite complete metabolic response (CMR), 2-Likely CMR, 3-Likely inflammatory, 4-Likely residual metabolic disease (RMD), and 5-Definite RMD. 'Negative'= 1 or 2, 'Indeterminate'=3, 'Positive' = 4 or 5. 'Negative' for all three evaluation sites = overall score of 'Negative.' Progression (failure) is defined as local, regional, or distant disease progression (PR) or any death. Local-regional progression (failure) is defined as local or regional PR, salvage surgery of the primary tumor with tumor present/unknown, salvage neck dissection with tumor present/unknown > 20 weeks post RT, death due to study cancer or unknown causes without documented PR. The protocol specified that both arms would be combined for analysis.	3 months (scan) and two years after the end of RT (approximately 6 weeks for Arm 1 and 5 weeks for Arm 2)
Human Papillomavirus (HPV) Deoxyribonucleic Acid (DNA) Detection Rate	With a two-sided type error rate of 5% and based on chi-squared test for proportions, there is a greater than 99% power to detect HPV DNA detection rate of 65% and 95% between the 2 groups (n=140 in each arm). The rate of detection for each group will be summarized based on binomial distributions and a 95% confidence intervals (CI) will be provided.	Baseline to up to 2 weeks after the completion of treatment
HPV DNA Rate Decline	With a two-sided type error rate of 5% and based on paired t test for means, there is 99% power to detect HPV DNA rate decline of 0.375 (effect size) within each arm (n=140). The HPV DNA rate for each group will be summarized using means and standard deviations.	Baseline to up to 2 weeks after the completion of treatment
HPV DNA Copy Number	Correlation between HPV DNA copy number and the nodal metabolic volume will be calculated using Spearman's correlation coefficient and R2, and the corresponding 95% CI will be provided.	Baseline to up to 2 weeks after the completion of treatment
Variance for HPV DNA	Univariable and multivariable cause specific analysis will be performed using the Cox proportional hazards model for rate of relapse.	Baseline to up to 2 weeks after the completion of treatment

Collaborators and Investigators

• Sponsor: NRG Oncology
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Sue Yom, NRG Oncology

Publications and helpful links

General Publications

• Yom SS, Torres-Saavedra P, Caudell JJ, Waldron JN, Gillison ML, Xia P, Truong MT, Kong C, Jordan R, Subramaniam RM, Yao M, Chung CH, Geiger JL, Chan JW, O'Sullivan B, Blakaj DM, Mell LK, Thorstad WL, Jones CU, Banerjee RN, Lominska C, Le QT. Reduced-Dose Radiation Therapy for HPV-Associated Oropharyngeal Carcinoma (NRG Oncology HN002). J Clin Oncol. 2021 Mar 20;39(9):956-965. doi: 10.1200/JCO.20.03128. Epub 2021 Jan 28.

Study record dates

Study Major Dates

• Study Start: October 1, 2014
• Primary Completion (Actual): June 10, 2019
• Study Completion (Estimated): May 31, 2024

Study Registration Dates

• First Submitted: September 29, 2014
• First Submitted That Met QC Criteria: September 29, 2014
• First Posted (Estimated): October 1, 2014

Study Record Updates

• Last Update Posted (Actual): September 22, 2023
• Last Update Submitted That Met QC Criteria: September 13, 2023
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Head and Neck Neoplasms; Pharyngeal Diseases; Stomatognathic Diseases; Otorhinolaryngologic Diseases; Neoplasms, Squamous Cell; Carcinoma; Carcinoma, Squamous Cell; Squamous Cell Carcinoma of Head and Neck; Oropharyngeal Neoplasms; Antineoplastic Agents; Cisplatin
• Other Study ID Numbers: NRG-HN002 (Other Identifier: CTEP); U10CA180868 (U.S. NIH Grant/Contract); NCI-2014-01279 (Registry Identifier: CTRP (Clinical Trial Reporting Program))