Radiation Therapy With Durvalumab or Cetuximab in Treating Patients With Locoregionally Advanced Head and Neck Cancer Who Cannot Take Cisplatin

May 29, 2026 updated by: National Cancer Institute (NCI)

Randomized Phase II/III Trial of Radiotherapy With Concurrent MEDI4736 (Durvalumab) vs. Radiotherapy With Concurrent Cetuximab in Patients With Locoregionally Advanced Head and Neck Cancer With a Contraindication to Cisplatin

This phase II/III trial studies how well radiation therapy works with durvalumab or cetuximab in treating patients with head and neck cancer that has spread to a local and/or regional area of the body who cannot take cisplatin. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Immunotherapy with monoclonal antibodies, such as durvalumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Cetuximab is a monoclonal antibody that may interfere with the ability of tumor cells to grow and spread. It is not known if radiation therapy with durvalumab will work better than the usual therapy of radiation therapy with cetuximab in treating patients with head and neck cancer.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

PRIMARY OBJECTIVES:

I. To determine the safety of radiotherapy (RT) with concurrent and adjuvant anti-PD-L1 therapy (MEDI4736 [durvalumab]) is safe in patients with locoregionally advanced head and neck cancer (HNC) who have a contraindication to cisplatin. (Lead-in) II. To test the hypothesis that concurrent RT and anti-PD-L1 therapy improves progression free survival (PFS) compared to standard therapy (RT with concurrent cetuximab) in patients with locoregionally advanced HNC who have a contraindication to cisplatin. (Phase II) III. To test the hypothesis that concurrent RT and anti-PD-L1 therapy improves overall survival compared to standard therapy (RT with concurrent cetuximab) in patients with locoregionally advanced HNC who have a contraindication to cisplatin. (Phase III)

SECONDARY OBJECTIVES:

I. To compare toxicity using Common Terminology Criteria for Adverse Events (CTCAE) and Patient Reported Outcomes (PRO)-CTCAE between patients treated with RT + anti-PD-L1 therapy versus RT/cetuximab.

II. To test the effect of anti-PD-L1 therapy in the subpopulation of patients with tumors that overexpress PD-L1.

III. To compare overall survival, response (at 4-month fludeoxyglucose F-18 [FDG]-positron emission tomography [PET]-computed tomography [CT]), locoregional failure, distant metastasis, and competing mortality in the two arms by known risk factors, including p16 status and omega score.

IV. To test the hypothesis that MEDI4736 (durvalumab) therapy arm will have less decline in the physical function domain of European Organization for Research and Treatment of Cancer Core Questionnaire (EORTC QLQ-C30 version 3.0) based on the change in score from baseline to 12 months from end of RT, compared to the cetuximab-RT arm in patients with locoregionally advanced HNC who have a contraindication to cisplatin.

V. To test the hypothesis that MEDI4736 (durvalumab) therapy arm at 1 year (from end of RT) will have less decline in swallowing related quality of life (QOL) using the M. D. Anderson Dysphagia Inventory (MDADI) total composite score, based on the change in score from baseline to 12 months from end of RT, compared to the cetuximab-RT arm in patients who are medically unfit for cisplatin.

VI. To compare swallowing related performance and function short and long term using the Performance Status Scale for Head & Neck Cancer Patients (PSS-HN).

VII. To evaluate gastrostomy tube retention rates between arms.

EXPLORATORY OBJECTIVES:

I. To test the hypothesis that radiation combined with MEDI4736 (durvalumab) enhances the adaptive immune response using three types of immunophenotyping compared to radiation combined with cetuximab.

II. To compare overall QOL short term (end RT-8 months) and long term (12-24 months from end of RT) between arms using the EORTC QLQ-C30 version 3.0/HN35.

III. To evaluate swallowing related QOL short term (end RT-8 months) and long term (12-24 months from end of RT) using the EORTC Head and Neck (HN)35 swallowing domain and MDADI (subscales) between arms in patients with locoregionally advanced HNC who have a contraindication to cisplatin.

IV. To evaluate patient reported fatigue using the fatigue items in the EORTC QLQ and PRO-CTCAE.

V. To compare clinician and patient reported toxicity using CTCAE and PRO CTCAE.

VI. To explore health utilities between cetuximab and MEDI4736 (durvalumab) RT using the European Quality of Life 5 Dimensional-5 Level (EQ5D-5L).

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM I: Patients receive cetuximab intravenously (IV) weekly over 60-120 minutes. Treatment repeats every week for up to 8 cycles in the absence of disease progression or unacceptable toxicity. Beginning 5-7 days after first cetuximab dose, patients undergo intensity modulated radiation therapy (IMRT) 5 fractions per week for up to 7 weeks.

ARM II: Patients receive durvalumab IV over 60 minutes every 4 weeks. Treatment repeats every 4 weeks for up to 7 cycles in the absence of disease progression or unacceptable toxicity. Beginning week 2, patients undergo IMRT 5 fractions per week for up to 7 weeks.

After completion of study treatment, patients are followed up at 1 month, every 4 months for 1 year, every 6 months for 2 years, then annually thereafter.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
196

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • Ontario
      • London, Ontario, Canada, N6A 4L6
        • London Regional Cancer Program
      • Toronto, Ontario, Canada, M5G 2M9
        • University Health Network-Princess Margaret Hospital
    • Quebec
      • Montreal, Quebec, Canada, H3H 2R9
        • The Research Institute of the McGill University Health Centre (MUHC)
    • Saskatchewan
      • Regina, Saskatchewan, Canada, S4T 7T1
        • Allan Blair Cancer Centre
  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35233
        • University of Alabama at Birmingham Cancer Center
      • Mobile, Alabama, United States, 36688
        • University of South Alabama Mitchell Cancer Institute
    • Arizona
      • Gilbert, Arizona, United States, 85234
        • Banner MD Anderson Cancer Center
      • Goodyear, Arizona, United States, 85338
        • CTCA at Western Regional Medical Center
      • Tucson, Arizona, United States, 85719
        • Banner University Medical Center - Tucson
      • Tucson, Arizona, United States, 85719
        • University of Arizona Cancer Center-North Campus
    • California
      • Antioch, California, United States, 94531
        • Kaiser Permanente-Deer Valley Medical Center
      • Auburn, California, United States, 95603
        • Sutter Cancer Centers Radiation Oncology Services-Auburn
      • Berkeley, California, United States, 94704
        • Alta Bates Summit Medical Center-Herrick Campus
      • Duarte, California, United States, 91010
        • City of Hope Comprehensive Cancer Center
      • Dublin, California, United States, 94568
        • Kaiser Permanente Dublin
      • Fremont, California, United States, 94538
        • Kaiser Permanente-Fremont
      • Fresno, California, United States, 93720
        • Kaiser Permanente-Fresno
      • Fresno, California, United States, 93720
        • Fresno Cancer Center
      • La Jolla, California, United States, 92093
        • UC San Diego Moores Cancer Center
      • Los Angeles, California, United States, 90048
        • Cedars Sinai Medical Center
      • Modesto, California, United States, 95356
        • Kaiser Permanente-Modesto
      • Oakland, California, United States, 94611
        • Kaiser Permanente-Oakland
      • Oakland, California, United States, 94611
        • Kaiser Permanente Oakland-Broadway
      • Palo Alto, California, United States, 94304
        • VA Palo Alto Health Care System
      • Palo Alto, California, United States, 94304
        • Stanford Cancer Institute Palo Alto
      • Rancho Cordova, California, United States, 95670
        • Kaiser Permanente-Rancho Cordova Cancer Center
      • Richmond, California, United States, 94801
        • Kaiser Permanente-Richmond
      • 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
        • Kaiser Permanente-Roseville
      • 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, 95814
        • Kaiser Permanente Downtown Commons
      • Sacramento, California, United States, 95823
        • Kaiser Permanente-South Sacramento
      • Sacramento, California, United States, 95823
        • South Sacramento Cancer Center
      • San Francisco, California, United States, 94115
        • Kaiser Permanente-San Francisco
      • San Francisco, California, United States, 94158
        • UCSF Medical Center-Mission Bay
      • San Francisco, California, United States, 94115
        • UCSF Medical Center-Mount Zion
      • San Jose, California, United States, 95119
        • Kaiser Permanente-Santa Teresa-San Jose
      • San Leandro, California, United States, 94577
        • Kaiser Permanente San Leandro
      • San Rafael, California, United States, 94903
        • Kaiser San Rafael-Gallinas
      • Santa Clara, California, United States, 95051
        • Kaiser Permanente Medical Center - Santa Clara
      • Santa Rosa, California, United States, 95403
        • Kaiser Permanente-Santa Rosa
      • South Pasadena, California, United States, 91030
        • City of Hope South Pasadena
      • South San Francisco, California, United States, 94080
        • Kaiser Permanente Cancer Treatment Center
      • South San Francisco, California, United States, 94080
        • Kaiser Permanente-South San Francisco
      • Stockton, California, United States, 95210
        • Kaiser Permanente-Stockton
      • Torrance, California, United States, 90509
        • Torrance Memorial Medical Center
      • Torrance, California, United States, 90505
        • Torrance Memorial Physician Network - Cancer Care
      • Truckee, California, United States, 96161
        • Gene Upshaw Memorial Tahoe Forest Cancer Center
      • Vacaville, California, United States, 95688
        • Kaiser Permanente Medical Center-Vacaville
      • Vallejo, California, United States, 94589
        • Kaiser Permanente-Vallejo
      • Walnut Creek, California, United States, 94596
        • Kaiser Permanente-Walnut Creek
    • Colorado
      • Aurora, Colorado, United States, 80045
        • UCHealth University of Colorado Hospital
      • Colorado Springs, Colorado, United States, 80907
        • Penrose-Saint Francis Healthcare
      • Colorado Springs, Colorado, United States, 80909
        • UCHealth Memorial Hospital Central
      • Colorado Springs, Colorado, United States, 80920
        • Memorial Hospital North
      • Fort Collins, Colorado, United States, 80524
        • Poudre Valley Hospital
      • Loveland, Colorado, United States, 80539
        • Banner McKee Medical Center
    • Connecticut
      • Hamden, Connecticut, United States, 06518
        • Smilow Cancer Hospital-Hamden Care Center
      • New Haven, Connecticut, United States, 06520
        • Yale University
      • Trumbull, Connecticut, United States, 06611
        • Smilow Cancer Hospital Care Center-Trumbull
      • Waterford, Connecticut, United States, 06385
        • Smilow Cancer Hospital Care Center - Waterford
    • Delaware
      • Millville, Delaware, United States, 19967
        • Beebe South Coastal Health Campus
      • Newark, Delaware, United States, 19713
        • Helen F Graham Cancer Center
      • Rehoboth Beach, Delaware, United States, 19971
        • Beebe Health Campus
    • Florida
      • Coral Gables, Florida, United States, 33146
        • UM Sylvester Comprehensive Cancer Center at Coral Gables
      • Deerfield Beach, Florida, United States, 33442
        • UM Sylvester Comprehensive Cancer Center at Deerfield Beach
      • Jacksonville, Florida, United States, 32207
        • Baptist MD Anderson Cancer Center
      • Miami, Florida, United States, 33136
        • University of Miami Miller School of Medicine-Sylvester Cancer Center
      • Tampa, Florida, United States, 33612
        • Moffitt Cancer Center
    • 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, 30303
        • Grady Health System
      • Augusta, Georgia, United States, 30912
        • Augusta University Medical Center
    • Hawaii
      • Honolulu, Hawaii, United States, 96813
        • Queen's Medical Center
      • Honolulu, Hawaii, United States, 96817
        • The Cancer Center of Hawaii-Liliha
      • Honolulu, Hawaii, United States, 96813
        • Hawaii Cancer Care Inc - Waterfront Plaza
    • Idaho
      • Caldwell, Idaho, United States, 83605
        • Saint Alphonsus Cancer Care Center-Caldwell
      • Nampa, Idaho, United States, 83687
        • Saint Alphonsus Cancer Care Center-Nampa
    • Illinois
      • Chicago, Illinois, United States, 60611
        • Northwestern University
      • Chicago, Illinois, United States, 60612
        • Rush University Medical Center
      • Chicago, Illinois, United States, 60612
        • University of Illinois
      • Chicago, Illinois, United States, 60612
        • John H Stroger Jr Hospital of Cook County
      • Decatur, Illinois, United States, 62526
        • Decatur Memorial Hospital
      • Effingham, Illinois, United States, 62401
        • Crossroads Cancer Center
      • Galesburg, Illinois, United States, 61401
        • Western Illinois Cancer Treatment Center
      • Peoria, Illinois, United States, 61636
        • Methodist Medical Center of Illinois
      • Peoria, Illinois, United States, 61637
        • OSF Saint Francis Medical Center
      • Springfield, Illinois, United States, 62781
        • Springfield Memorial Hospital
      • Urbana, Illinois, United States, 61801
        • Carle Cancer Center
    • Indiana
      • Carmel, Indiana, United States, 46032
        • IU Health North Hospital
      • Fort Wayne, Indiana, United States, 46805
        • Parkview Hospital Randallia
      • Fort Wayne, Indiana, United States, 46845
        • Parkview Regional Medical Center
      • Indianapolis, Indiana, United States, 46202
        • Indiana University/Melvin and Bren Simon Cancer Center
      • Indianapolis, Indiana, United States, 46219
        • Community Cancer Center East
      • Indianapolis, Indiana, United States, 46227
        • Community Cancer Center South
      • Indianapolis, Indiana, United States, 46256
        • Community Cancer Center North
      • Indianapolis, Indiana, United States, 46202
        • Sidney and Lois Eskenazi Hospital
    • Iowa
      • Clive, Iowa, United States, 50325
        • Mercy Cancer Center-West Lakes
      • Des Moines, Iowa, United States, 50309
        • Iowa Methodist Medical Center
      • Des Moines, Iowa, United States, 50314
        • Mercy Medical Center - Des Moines
    • Kansas
      • Kansas City, Kansas, United States, 66160
        • University of Kansas Cancer Center
      • Overland Park, Kansas, United States, 66210
        • University of Kansas Cancer Center-Overland Park
      • Salina, Kansas, United States, 67401
        • Salina Regional Health Center
      • Westwood, Kansas, United States, 66205
        • University of Kansas Hospital-Westwood Cancer Center
      • Wichita, Kansas, United States, 67214
        • Ascension Via Christi Hospitals Wichita
    • Kentucky
      • Lexington, Kentucky, United States, 40536
        • University of Kentucky/Markey Cancer Center
      • Louisville, Kentucky, United States, 40202
        • Norton Hospital Pavilion and Medical Campus
      • Louisville, Kentucky, United States, 40202
        • The James Graham Brown Cancer Center at University of Louisville
      • Louisville, Kentucky, United States, 40241
        • Norton Brownsboro Hospital and Medical Campus
    • Louisiana
      • Metairie, Louisiana, United States, 70006
        • East Jefferson General Hospital
    • 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
        • Trinity Health Saint Joseph Mercy Hospital Ann Arbor
      • Bay City, Michigan, United States, 48706
        • McLaren Cancer Institute-Bay City
      • Brighton, Michigan, United States, 48114
        • Trinity Health Medical Center - Brighton
      • Brownstown, Michigan, United States, 48183
        • Henry Ford Cancer Institute-Downriver
      • Canton, Michigan, United States, 48188
        • Trinity Health Medical Center - Canton
      • Chelsea, Michigan, United States, 48118
        • Chelsea Hospital
      • Clarkston, Michigan, United States, 48346
        • McLaren Cancer Institute-Clarkston
      • Clinton Township, Michigan, United States, 48038
        • Henry Ford Macomb Hospital-Clinton Township
      • Detroit, Michigan, United States, 48202
        • Henry Ford Hospital
      • Detroit, Michigan, United States, 48201
        • Wayne State University/Karmanos Cancer Institute
      • Farmington Hills, Michigan, United States, 48334
        • Weisberg Cancer Treatment Center
      • Flint, Michigan, United States, 48532
        • McLaren Cancer Institute-Flint
      • Flint, Michigan, United States, 48532
        • Singh and Arora Hematology Oncology PC
      • Jackson, Michigan, United States, 49201
        • Allegiance Health
      • Lansing, Michigan, United States, 48912
        • Mid-Michigan Physicians-Lansing
      • Lansing, Michigan, United States, 48910
        • Karmanos Cancer Institute at McLaren Greater Lansing
      • Lansing, Michigan, United States, 48912
        • University of Michigan Health - Sparrow Lansing
      • Lapeer, Michigan, United States, 48446
        • McLaren Cancer Institute-Lapeer Region
      • Mount Clemens, Michigan, United States, 48043
        • McLaren Cancer Institute-Macomb
      • Petoskey, Michigan, United States, 49770
        • McLaren Cancer Institute-Northern Michigan
      • Port Huron, Michigan, United States, 48060
        • McLaren-Port Huron
      • Saginaw, Michigan, United States, 48601
        • MyMichigan Medical Center Saginaw
      • West Bloomfield, Michigan, United States, 48322
        • Henry Ford West Bloomfield Hospital
    • Minnesota
      • Bemidji, Minnesota, United States, 56601
        • Sanford Joe Lueken Cancer Center
      • Burnsville, Minnesota, United States, 55337
        • Fairview Ridges Hospital
      • Duluth, Minnesota, United States, 55805
        • Miller-Dwan Hospital
      • Edina, Minnesota, United States, 55435
        • Fairview Southdale Hospital
      • Fridley, Minnesota, United States, 55432
        • Unity Hospital
      • Minneapolis, Minnesota, United States, 55415
        • Hennepin County Medical Center
      • Rochester, Minnesota, United States, 55905
        • Mayo Clinic in Rochester
      • Saint Cloud, Minnesota, United States, 56303
        • Coborn Cancer Center at Saint Cloud Hospital
      • Saint Paul, Minnesota, United States, 55101
        • Regions Hospital
    • Missouri
      • Cape Girardeau, Missouri, United States, 63703
        • Saint Francis Medical Center
      • City of Saint Peters, Missouri, United States, 63376
        • Siteman Cancer Center at Saint Peters Hospital
      • Creve Coeur, Missouri, United States, 63141
        • Siteman Cancer Center at West County Hospital
      • St Louis, Missouri, United States, 63110
        • Washington University School of Medicine
      • St Louis, Missouri, United States, 63141
        • Mercy Hospital Saint Louis
    • Montana
      • Billings, Montana, United States, 59101
        • Billings Clinic Cancer Center
      • Kalispell, Montana, United States, 59901
        • Logan Health Medical Center
    • Nebraska
      • Grand Island, Nebraska, United States, 68803
        • Nebraska Cancer Specialists/Oncology Hematology West PC
    • New Hampshire
      • Lebanon, New Hampshire, United States, 03756
        • Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center
    • New Jersey
      • Basking Ridge, New Jersey, United States, 07920
        • Memorial Sloan Kettering Basking Ridge
      • Hackensack, New Jersey, United States, 07601
        • Hackensack University Medical Center
      • Middletown, New Jersey, United States, 07748
        • Memorial Sloan Kettering Monmouth
      • Montvale, New Jersey, United States, 07645
        • Memorial Sloan Kettering Bergen
    • New Mexico
      • Albuquerque, New Mexico, United States, 87109
        • New Mexico Oncology Hematology Consultants
      • Albuquerque, New Mexico, United States, 87106
        • University of New Mexico Cancer Center
    • New York
      • Buffalo, New York, United States, 14263
        • Roswell Park Cancer Institute
      • 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
      • New York, New York, United States, 10032
        • NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
      • New York, New York, United States, 10016
        • Laura and Isaac Perlmutter Cancer Center at NYU Langone
      • Rochester, New York, United States, 14642
        • University of Rochester
      • Stony Brook, New York, United States, 11794
        • Stony Brook University Medical Center
      • Syracuse, New York, United States, 13210
        • State University of New York Upstate Medical University
      • The Bronx, New York, United States, 10467
        • Montefiore Medical Center - Moses Campus
      • The Bronx, New York, United States, 10468
        • James J Peters VA Medical Center
      • Uniondale, New York, United States, 11553
        • Memorial Sloan Kettering Nassau
    • North Carolina
      • Albemarle, North Carolina, United States, 28002
        • Atrium Health Stanly/LCI-Albemarle
      • Chapel Hill, North Carolina, United States, 27599
        • UNC Lineberger Comprehensive Cancer Center
      • Charlotte, North Carolina, United States, 28203
        • Carolinas Medical Center/Levine Cancer Institute
      • Charlotte, North Carolina, United States, 28210
        • Atrium Health Pineville/LCI-Pineville
      • Concord, North Carolina, United States, 28025
        • Atrium Health Cabarrus/LCI-Concord
      • Hendersonville, North Carolina, United States, 28791
        • Margaret R Pardee Memorial Hospital
      • Monroe, North Carolina, United States, 28112
        • Atrium Health Union/LCI-Union
    • North Dakota
      • Fargo, North Dakota, United States, 58122
        • Sanford Roger Maris Cancer Center
    • Ohio
      • Canton, Ohio, United States, 44708
        • Cleveland Clinic Mercy Hospital
      • Canton, Ohio, United States, 44710
        • Aultman Health Foundation
      • Chardon, Ohio, United States, 44024
        • Geauga Hospital
      • Cincinnati, Ohio, United States, 45219
        • University of Cincinnati Cancer Center-UC Medical Center
      • Cleveland, Ohio, United States, 44106
        • Case Western Reserve University
      • Cleveland, Ohio, United States, 44109
        • MetroHealth Medical Center
      • Cleveland, Ohio, United States, 44195
        • Cleveland Clinic Foundation
      • Columbus, Ohio, United States, 43210
        • Ohio State University Comprehensive Cancer Center
      • Mansfield, Ohio, United States, 44906
        • Cleveland Clinic Cancer Center Mansfield
      • Mentor, Ohio, United States, 44060
        • UH Seidman Cancer Center at Lake Health Mentor Campus
      • Sandusky, Ohio, United States, 44870
        • North Coast Cancer Care
      • Sylvania, Ohio, United States, 43560
        • ProMedica Flower Hospital
      • West Chester, Ohio, United States, 45069
        • University of Cincinnati Cancer Center-West Chester
      • 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
    • Oregon
      • Corvallis, Oregon, United States, 97330
        • Good Samaritan Hospital
      • Portland, Oregon, United States, 97213
        • Providence Portland Medical Center
      • Portland, Oregon, United States, 97225
        • Providence Saint Vincent Medical Center
      • Portland, Oregon, United States, 97227
        • Kaiser Permanente Northwest
    • Pennsylvania
      • Abington, Pennsylvania, United States, 19001
        • Jefferson Abington Hospital
      • Broomall, Pennsylvania, United States, 19008
        • Crozer-Keystone Regional Cancer Center at Broomall
      • Chadds Ford, Pennsylvania, United States, 19317
        • Christiana Care Health System-Concord Health Center
      • Danville, Pennsylvania, United States, 17822
        • Geisinger Medical Center
      • Hershey, Pennsylvania, United States, 17033-0850
        • Penn State Milton S Hershey Medical Center
      • Lewisburg, Pennsylvania, United States, 17837
        • Geisinger Medical Oncology-Lewisburg
      • Lewistown, Pennsylvania, United States, 17044
        • Lewistown Hospital
      • Monroeville, Pennsylvania, United States, 15146
        • Forbes Hospital
      • Philadelphia, Pennsylvania, United States, 19111
        • Fox Chase Cancer Center
      • Philadelphia, Pennsylvania, United States, 19140
        • Temple University Hospital
      • Pittsburgh, Pennsylvania, United States, 15212
        • Allegheny General Hospital
      • Pittsburgh, Pennsylvania, United States, 15232
        • UPMC-Shadyside Hospital
      • Sayre, Pennsylvania, United States, 18840
        • Guthrie Medical Group PC-Robert Packer Hospital
      • West Reading, Pennsylvania, United States, 19611
        • Reading Hospital
      • Wexford, Pennsylvania, United States, 15090
        • Wexford Health and Wellness Pavilion
      • Wilkes-Barre, Pennsylvania, United States, 18711
        • Geisinger Wyoming Valley/Henry Cancer Center
      • Willow Grove, Pennsylvania, United States, 19090
        • Asplundh Cancer Pavilion
    • South Carolina
      • Charleston, South Carolina, United States, 29425
        • Medical University of South Carolina
      • Greer, South Carolina, United States, 29651
        • Gibbs Cancer Center-Pelham
      • Rock Hill, South Carolina, United States, 29730
        • Rock Hill Radiation Therapy Center
      • Spartanburg, South Carolina, United States, 29303
        • Spartanburg Medical Center
    • South Dakota
      • Sioux Falls, South Dakota, United States, 57105
        • Avera Cancer Institute
      • Sioux Falls, South Dakota, United States, 57117-5134
        • Sanford USD Medical Center - Sioux Falls
    • Texas
      • Houston, Texas, United States, 77030
        • M D Anderson Cancer Center
    • Vermont
      • Saint Johnsbury, Vermont, United States, 05819
        • Dartmouth Cancer Center - North
    • Virginia
      • Charlottesville, Virginia, United States, 22908
        • University of Virginia Cancer Center
      • Norfolk, Virginia, United States, 23507
        • Sentara Norfolk General Hospital
      • Richmond, Virginia, United States, 23235
        • VCU Massey Cancer Center at Stony Point
      • Richmond, Virginia, United States, 23298
        • VCU Massey Comprehensive Cancer Center
    • Washington
      • Seattle, Washington, United States, 98195
        • University of Washington Medical Center - Montlake
    • West Virginia
      • Morgantown, West Virginia, United States, 26506
        • West Virginia University Healthcare
    • Wisconsin
      • Antigo, Wisconsin, United States, 54409
        • Langlade Hospital and Cancer Center
      • Green Bay, Wisconsin, United States, 54311
        • Aurora BayCare Medical Center
      • 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
        • University of Wisconsin Carbone Cancer Center - Johnson Creek
      • Kenosha, Wisconsin, United States, 53142
        • Aurora Cancer Care-Kenosha South
      • La Crosse, Wisconsin, United States, 54601
        • Gundersen Lutheran Medical Center
      • Madison, Wisconsin, United States, 53792
        • University of Wisconsin Carbone Cancer Center - University Hospital
      • Marinette, Wisconsin, United States, 54143
        • Aurora Bay Area Medical Group-Marinette
      • Menomonee Falls, Wisconsin, United States, 53051
        • Froedtert Menomonee Falls Hospital
      • Milwaukee, Wisconsin, United States, 53226
        • Medical College of Wisconsin
      • Milwaukee, Wisconsin, United States, 53215
        • Aurora Saint Luke's Medical Center
      • Milwaukee, Wisconsin, United States, 53295
        • Zablocki Veterans Administration Medical Center
      • Mukwonago, Wisconsin, United States, 53149
        • ProHealth D N Greenwald Center
      • Oconomowoc, Wisconsin, United States, 53066
        • ProHealth Oconomowoc Memorial Hospital
      • Sheboygan, Wisconsin, United States, 53081
        • Vince Lombardi Cancer Clinic-Sheboygan
      • Summit, Wisconsin, United States, 53066
        • Aurora Medical Center in Summit
      • Waukesha, Wisconsin, United States, 53188
        • UW Cancer Center at ProHealth Care
      • Wausau, Wisconsin, United States, 54401
        • Aspirus Regional Cancer Center
      • West Allis, Wisconsin, United States, 53227
        • Aurora West Allis Medical Center
      • West Bend, Wisconsin, United States, 53095
        • Froedtert West Bend Hospital/Kraemer Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • PRIOR TO STEP 1 REGISTRATION INCLUSION CRITERIA

  • Patients must have pathologically confirmed, previously untreated, unresected squamous cell carcinoma of the larynx, hypopharynx, oropharynx, oral cavity, or carcinoma of unknown head/neck primary prior to step 1 registration; submission of hematoxylin and eosin (H&E) stained slides and formalin-fixed and paraffin-embedded (FFPE) tissue block (or punch biopsy of FFPE block) to the biospecimen bank at University of California, San Francisco (UCSF) for central review for oropharyngeal and unknown primaries and for p16 analysis for all other non-oropharyngeal primaries is mandatory for all patients; investigators should check with their pathology department regarding release of biospecimens before approaching patients about participation in the trial; for oropharyngeal and unknown primaries, submission of H&E and p16 stained slides (with the required block for PD-L1) to the biospecimen bank at UCSF for central review is also required prior to step 2 registration

    • Note: fine needle aspirates (FNA) samples are not acceptable since they do not provide enough material for PD-L1 and p16 testing; however, if a cell block derived from the FNA is available, it is allowable if there are sufficient cells present in the block for PD-L1 testing; Dr. Jordan will determine this upon receipt; for sites submitting FNA cell blocks for ALL patients they must do so within 7-10 business days from registering the patient; sites must confirm with their cytology/pathology labs to make sure they can provide the required material as the bank must be able to retain these samples for the mandatory testing

  • Patients must have locoregionally advanced head and neck squamous cell carcinoma (HNSCC)

    • For p16-positive oropharyngeal/unknown primaries, American Joint Committee on Cancer [AJCC] 8th edition stage III and selected stage I-II based on smoking status in pack-years
    • For laryngeal, hypopharyngeal, and oral cavity primaries and p16-negative oropharyngeal/unknown primaries, AJCC 8th edition stage III-IVB

    • Based on the following minimum diagnostic workup within 60 days prior to step 1 registration:

      • General history and physical examination by a radiation oncologist or medical oncologist or ear, nose and throat (ENT) or head & neck surgeon
      • For larynx, hypopharynx, and base of tongue primaries, a laryngopharyngoscopy (mirror and/or fiberoptic and/or direct procedure) is required, unless the patient cannot tolerate or refuses
    • Imaging of the head and neck with a neck CT or magnetic resonance imaging (MRI) (with contrast, unless contraindicated) or PET/CT; note that the CT portion of the PET/CT must be of diagnostic quality, including contrast administration unless contraindicated. If the CT portion of the PET/CT study is low-dose (non-diagnostic), then an additional CT or MRI study with contrast (unless contraindicated) is required
    • Chest imaging: chest CT with and without contrast (unless contraindicated) or PET/CT

  • Patients must have a contraindication to cisplatin as defined in the following bullet points; sites must complete the online tool at comogram.org prior to step 1 registration to determine if the patient is eligible; the scores must be recorded on a case report form (CRF)

    • Age >= 70 with moderate to severe comorbidity or vulnerability to cisplatin, defined as having one or more of the following conditions within 30 days prior to step 1 registration:

      • Modified Charlson Comorbidity Index >= 1
      • Adult Comorbidity Evaluation (ACE)-27 Index >= 1
      • Generalized Competing Event Model for Cancer Risk (GCE) omega PFS score < 0.80
      • Geriatric screening (G-8) score =< 14
      • Cancer and Aging Research Group (CARG) toxicity score >= 30%
      • Cumulative Illness Rating scale for Geriatrics (CIRS-G) score >= 4 OR

    • Age < 70 with severe comorbidity or vulnerability to cisplatin, defined as having two or more of the following conditions within 30 days prior to step 1 registration

      • Modified Charlson Comorbidity Index >= 1
      • ACE-27 Index >= 1
      • GCE omega PFS-score < 0.80
      • G-8 score =< 14
      • CARG Toxicity score >= 30%
      • CIRS-G score >= 4 OR

    • Age >= 18 with an absolute or relative contraindication to cisplatin, defined as one or more of the following within 30 days prior to step 1 registration:

      • Creatinine clearance (CC) > 30 and < 60 cc/min; for this calculation, use the Cockcroft-Gault formula
      • Zubrod performance status 2 prior to step 1 registration
      • Pre-existing peripheral neuropathy grade >= 1

      • History of hearing loss, defined as either:

        • Existing need of a hearing aid OR
        • >= 25 decibel shift over 2 contiguous frequencies on a pretreatment hearing test as clinically indicated
  • Absolute neutrophil count (ANC) >= 1,000 cells/mm^3 (within 14 days prior to step 1 registration)
  • Platelets >= 100,000 cells/mm^3 (within 14 days prior to step 1 registration)
  • Hemoglobin >= 9.0 g/dl (Note: the use of transfusion or other intervention to achieve hemoglobin [Hgb] >= 9.0 g/dl is acceptable) (within 14 days prior to step 1 registration)
  • Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) =< 2.5 times institutional upper limit of normal (within 14 days prior to step 1 registration)
  • Serum bilirubin =< 1.5 x institutional upper limit of normal (within 14 days prior to step 1 registration)
  • Measured creatinine clearance (CL) > 30 mL/min or calculated creatinine CL > 30 mL/min by the Cockcroft-Gault formula (Cockcroft and Gault 1976) or by 24-hour urine collection for determination of creatinine clearance (within 14 days prior to step 1 registration)

  • For women of childbearing potential, a negative serum or urine pregnancy test within 14 days prior to step 1 registration; Note: women will be considered post-menopausal if they have been amenorrheic for 12 months without an alternative medical cause; the following age-specific requirements apply:

    • Women < 50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and if they have luteinizing hormone and follicle-stimulating hormone levels in the post-menopausal range for the institution or underwent surgical sterilization (bilateral oophorectomy or hysterectomy)
    • Women >= 50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of all exogenous hormonal treatments, had radiation-induced menopause with last menses > 1 year ago, had chemotherapy-induced menopause with last menses > 1 year ago, or underwent surgical sterilization (bilateral oophorectomy, bilateral salpingectomy or hysterectomy)
  • The patient or a legally authorized representative must provide study-specific informed consent prior to step 1 registration
  • PRIOR TO STEP 2 REGISTRATION INCLUSION CRITERIA

  • For patients with oropharyngeal or unknown primaries: p16 determination by immunohistochemistry (defined as greater than 70% strong nuclear or nuclear and cytoplasmic staining of tumor cells), confirmed by central pathology review

    • Note: for patients with oral cavity, laryngeal, and hypopharyngeal primaries, analysis of p16 status prior to step 2 registration/randomization is not required (p16 status will be analyzed centrally post-hoc); step 2 registration for these patients can be completed after step 1 registration

Exclusion Criteria:

  • PRIOR TO STEP 1 REGISTRATION EXCLUSION CRITERIA
  • Prior invasive malignancy within the past 3 years (except for non-melanomatous skin cancer, and early stage treated prostate cancer); synchronous head and neck primaries are ineligible

  • Prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields

    • Note: Prior external beam radiotherapy is excluded, but iodine 131 is allowed
  • Prior immunotherapy
  • Prior systemic therapy, including cytotoxic chemotherapy, biologic/targeted therapy, or immune therapy for the study cancer
  • Major surgery within 28 days prior to step 1 registration
  • Proven evidence of distant metastases

  • If both of the following conditions are present, the patient is ineligible:

    • =< 10 pack-year smoking history

    • p16-positive carcinoma of the oropharynx or unknown primary that are T0-3, N0-1 (AJCC 8th Edition)

      • Note: in the event that a registered patient with =< 10 pack-years has a p16-positive result on central review with the tumor and nodal stage T0-3, N0-1 (AJCC 8th Edition), then the site will be notified that the patient is ineligible
  • Zubrod performance status >= 3
  • Body weight =< 30 kg
  • Patients with oral cavity cancer are excluded from participation if the patient is medically operable and resection of the primary tumor is considered technically feasible by an oral or head and neck cancers surgical subspecialist;(please consult the surgical oncology co-principal investigator [PI], Steven Chang, Doctor of Medicine [MD], if clarification is needed on an individual case)
  • Sodium < 130 mmol/L or > 155 mmol/L (within 14 days of step 1 registration, unless corrected prior to step 1 registration)
  • Potassium < 3.5 mmol/L or > 6 mmol/L (within 14 days of step 1 registration, unless corrected prior to step 1 registration)
  • Fasting glucose < 40 mg/dl or > 400 mg/dl (within 14 days of step 1 registration, unless corrected prior to step 1 registration)
  • Serum calcium (ionized or adjusted for albumin) < 7 mg/dl or > 12.5 mg/dl (within 14 days of step 1 registration, unless corrected prior to step 1 registration)
  • Magnesium < 0.9 mg/dl or > 3 mg/dl (within 14 days of step 1 registration, unless corrected prior to step 1 registration)
  • Unstable angina and/or congestive heart failure requiring hospitalization within 3 months prior to step 1 registration
  • Transmural myocardial infarction within 3 months prior to step 1 registration

  • Respiratory illness requiring hospitalization at the time of step 1 registration

    • Note: if the respiratory illness is resolved and the patient meets the eligibility status above, then the patient can be considered for the trial
  • Idiopathic pulmonary fibrosis or other severe interstitial lung disease that requires oxygen therapy or is thought to require oxygen therapy within 1 year prior to step 1 registration
  • History of (non-infectious) pneumonitis that required steroids or current pneumonitis
  • Clinically apparent jaundice and/or known coagulation defects

  • Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [e.g., colitis or Crohn's disease], diverticulitis [with the exception of diverticulosis], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome [granulomatosis with polyangiitis], Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc.)

    • The following are exceptions to this criterion:

      • Patients with vitiligo or alopecia;
      • Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement;
      • Any chronic skin condition that does not require systemic therapy;
      • Patients without active disease in the last 5 years may be included but only after consultation with the medical oncology study chair;
      • Patients with celiac disease controlled by diet alone
  • History of active primary immunodeficiency including, but not limited to acquired immune deficiency syndrome (AIDS) based upon current Centers for Disease Control and Prevention (CDC) definition; Note: human immunodeficiency virus (HIV) testing is not required for entry into this protocol; the need to exclude patients with AIDS from this protocol is necessary because the treatment involved in this protocol may be immunosuppressive; patients with known HIV, CD4 counts >= 200/uL, and undetectable viral loads who are stable on an antiretroviral regimen may be included
  • Current or prior use of immunosuppressive medication within 14 days before step 1 registration, with the exceptions of intranasal and inhaled corticosteroids or systemic corticosteroids at physiological doses, which are not to exceed 10 mg/day of prednisone, or an equivalent corticosteroid
  • Receipt of live attenuated vaccination within 30 days prior to step 1 registration
  • Medical or psychiatric illness which would compromise the patient's ability to tolerate treatment or limit compliance with study requirements
  • Pregnancy or women of childbearing potential and men who are sexually active and not willing/able to use medically acceptable forms of contraception during treatment and for 6 months after the last dose of cetuximab or MEDI14736 (durvalumab); this exclusion is necessary because the treatment involved in this study may be significantly teratogenic; women who are breastfeeding are also excluded
  • Prior allergic reaction or hypersensitivity to cetuximab or MEDI4736 (durvalumab) or any of study drug excipients
  • History of allogenic organ transplantation
  • Uncontrolled hypertension
  • Uncontrolled cardiac arrhythmia
  • Uncontrolled serious chronic gastrointestinal condition associated with diarrhea
  • Active infection including tuberculosis (clinical evaluation that includes clinical history, physical examination and radiographic findings, and tuberculosis [TB] testing in line with local practice), hepatitis B (known positive hepatitis B virus [HBV] surface antigen [HBsAg] result), hepatitis C; patients with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody [anti-HBc] and absence of HBsAg) are eligible; patients positive for hepatitis C (hepatitis C virus [HCV]) antibody are eligible only if polymerase chain reaction is negative for HCV ribonucleic acid (RNA)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Active Comparator: Arm I (cetuximab, radiation therapy)
Patients receive cetuximab IV weekly over 60-120 minutes. Treatment repeats every week for up to 8 cycles in the absence of disease progression or unacceptable toxicity. Beginning 5-7 days after first cetuximab dose, patients undergo IMRT 5 fractions per week for up to 7 weeks.
Other: Laboratory Biomarker Analysis
Correlative studies
Other: Quality-of-Life Assessment
Ancillary studies
Other Names:
  • Quality of Life Assessment
Other: Questionnaire Administration
Ancillary studies
Radiation: Intensity-Modulated Radiation Therapy
Undergo IMRT
Other Names:
  • IMRT
  • Intensity Modulated RT
  • Intensity-Modulated Radiotherapy
  • Radiation, Intensity-Modulated Radiotherapy
  • Intensity modulated radiation therapy (procedure)
Biological: Cetuximab
Given IV
Other Names:
  • C225
  • Erbitux
  • IMC-C225
  • Cetuximab Biosimilar CDP-1
  • Cetuximab Biosimilar CMAB009
  • Cetuximab Biosimilar KL 140
  • Chimeric Anti-EGFR Monoclonal Antibody
  • Chimeric MoAb C225
  • Chimeric Monoclonal Antibody C225
  • C-225
  • C 225
Experimental: Arm II (durvalumab, radiation therapy)
Patients receive durvalumab IV over 60 minutes every 4 weeks. Treatment repeats every 4 weeks for up to 7 cycles in the absence of disease progression or unacceptable toxicity. Beginning week 2, patients undergo IMRT 5 fractions per week for up to 7 weeks.
Other: Laboratory Biomarker Analysis
Correlative studies
Other: Quality-of-Life Assessment
Ancillary studies
Other Names:
  • Quality of Life Assessment
Other: Questionnaire Administration
Ancillary studies
Biological: Durvalumab
Given IV
Other Names:
  • Imfinzi
  • Immunoglobulin G1, Anti-(Human Protein B7-H1) (Human Monoclonal MEDI4736 Heavy Chain), Disulfide with Human Monoclonal MEDI4736 Kappa-chain, Dimer
  • MEDI-4736
  • MEDI4736
  • MEDI 4736
Radiation: Intensity-Modulated Radiation Therapy
Undergo IMRT
Other Names:
  • IMRT
  • Intensity Modulated RT
  • Intensity-Modulated Radiotherapy
  • Radiation, Intensity-Modulated Radiotherapy
  • Intensity modulated radiation therapy (procedure)

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Number of Participants With Dose-limiting Toxicity (DLT) [Lead-in Phase]
Time Frame: From start of durvalumab to 4 weeks after radiation therapy, approximately 13 weeks. Weekly during RT, at RT end, prior to adjuvant durvalumab, one month after end of RT.
DLTs were collected to verify the safety of durvalumab with RT in this population. Safety was determined if ≤ 2 of 8 participants in the cohort had any DLT, in which case the study would proceed to phase II with that dose schedule (DS). The probability for the DS to be deemed too toxic, given a true toxicity rate ≥ 45%, is at least 78%. With a true toxicity rate ≤ 20%, the probability for the DS do be deemed safe is 80%. The full DLT definition does not fit here, but includes all grade 5 AEs, grade 3 or 4 AEs definitely or probably related to durvalumab (DPRD) except for specified AEs and situations, and incomplete or > 2-week delay completing RT due to immune toxicity DPRD. AEs were graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0, which grade severity from 1=mild to 5=death. Two alternate DSs with a delayed 2nd dose (to reduce/avoid doses concurrent with RT) would be tried if the initial DS was too toxic.
From start of durvalumab to 4 weeks after radiation therapy, approximately 13 weeks. Weekly during RT, at RT end, prior to adjuvant durvalumab, one month after end of RT.
Progression-free Survival (Percentage of Participants Alive Without Progression) [Phase II Primary]
Time Frame: From randomization to last follow-up: weekly during RT, after end of RT: every 4 months for 1 year, every 6 months for 2 years, then annually. Additionally, every 4 weeks during adjuvant durvalumab. Maximum follow-up at time of analysis was 4.2 years.

Progression (failure) is defined as local, regional, or distant disease progression, or death from any cause. Progression was assessed by imaging, clinical assessment, or biopsy.

Failure time is defined as time from randomization to failure or last follow-up (censored). Failure rates are estimated using the Kaplan-Meier method. The protocol specifies that the distributions of failure times be compared between the arms, which is reported in the statistical analysis results. Two-year estimates are provided. Analysis was planned to occur after 69 failure events had been reported.
From randomization to last follow-up: weekly during RT, after end of RT: every 4 months for 1 year, every 6 months for 2 years, then annually. Additionally, every 4 weeks during adjuvant durvalumab. Maximum follow-up at time of analysis was 4.2 years.
Overall Survival (Percentage of Participants Alive) [Originally Phase III Primary / Now Phase II Secondary]
Time Frame: From randomization to last follow-up: weekly during RT, after end of RT: every 4 months for 1 year, every 6 months for 2 years, then annually. Additionally, every 4 weeks during adjuvant durvalumab. Maximum follow-up at time of analysis was 4.2 years.
Overall survival (OS) time is defined as time from randomization to the date of death from any cause or last known follow-up (censored). Overall survival rates are estimated by the Kaplan-Meier method. The protocol specifies that the distributions of failure times be compared between the arms, which is reported in the statistical analysis results. Two-year estimates are provided.
From randomization to last follow-up: weekly during RT, after end of RT: every 4 months for 1 year, every 6 months for 2 years, then annually. Additionally, every 4 weeks during adjuvant durvalumab. Maximum follow-up at time of analysis was 4.2 years.

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Locoregional Failure (Percentage of Participants With Locoregional Failure)
Time Frame: From randomization to last follow-up: weekly during RT, after end of RT: every 4 months for 1 year, every 6 months for 2 years, then annually. Additionally, every 4 weeks during adjuvant durvalumab. Maximum follow-up at time of analysis was 4.2 years.
Locoregional progression is defined as local or regional progression or recurrence, death due to study cancer or unknown causes without documented progression. Progression was assessed by imaging, clinical assessment, or biopsy. Failure time is defined as time from randomization to failure, distant metastasis (competing risk), deaths from other causes (competing risk), or last follow-up (censored). Failure rates are estimated using the cumulative incidence method. The protocol specifies that the distributions of failure times be compared between the arms, which is reported in the statistical analysis results. Two-year estimates are provided.
From randomization to last follow-up: weekly during RT, after end of RT: every 4 months for 1 year, every 6 months for 2 years, then annually. Additionally, every 4 weeks during adjuvant durvalumab. Maximum follow-up at time of analysis was 4.2 years.
Distant Metastasis (Percentage of Participants With Distant Metastasis)
Time Frame: From randomization to last follow-up: weekly during RT, after end of RT: every 4 months for 1 year, every 6 months for 2 years, then annually. Additionally, every 4 weeks during adjuvant durvalumab. Maximum follow-up at time of analysis was 4.2 years.
Failure is defined as the occurrence of distant metastasis. Failure time is defined as time from randomization to first occurrence of distant metastasis, local or regional progression or recurrence (competing risk), death (competing risk), or last follow-up (censored). Failure rates are estimated using the cumulative incidence method. The protocol specifies that the distributions of failure times be compared between the arms, which is reported in the statistical analysis results. Two-year estimates are provided.
From randomization to last follow-up: weekly during RT, after end of RT: every 4 months for 1 year, every 6 months for 2 years, then annually. Additionally, every 4 weeks during adjuvant durvalumab. Maximum follow-up at time of analysis was 4.2 years.
Competing Mortality (Percentage of Participants Who Died Due to Causes Other Than Study Cancer)
Time Frame: From randomization to last follow-up: weekly during RT, after end of RT: every 4 months for 1 year, every 6 months for 2 years, then annually. Additionally, every 4 weeks during adjuvant durvalumab. Maximum follow-up at time of analysis was 4.2 years.
Failure is defined as Death from second primary, protocol treatment, or "other cause". Failure time is defined as time from randomization to first occurrence of failure, death due to study cancer or unknown cause (competing risk), or last follow-up (censored). Failure rates are estimated using the cumulative incidence method. The protocol specifies that the distributions of failure times be compared between the arms, which is reported in the statistical analysis results. Two-year estimates are provided.
From randomization to last follow-up: weekly during RT, after end of RT: every 4 months for 1 year, every 6 months for 2 years, then annually. Additionally, every 4 weeks during adjuvant durvalumab. Maximum follow-up at time of analysis was 4.2 years.
Percentage of Participants With Complete or Partial Response at 4-month Scan Determined by Response Evaluation Criteria in Solid Tumors (RECIST) v. 1.1
Time Frame: Baseline and 4 months after end of RT (approximately 6.5 months)

Fludeoxyglucose F-18 positron emission tomography/computed tomography (FDG-PET/CT) scans at baseline and four months after the end of radiation therapy are compared.

Per RECIST 1.1:

  • Complete response:

    • Disappearance of all lesions and pathologic lymph nodes

  • Partial response:

    • ≥ 30% decrease sum of the longest diameters
    • No new lesions
    • No progression of non-target lesions
Baseline and 4 months after end of RT (approximately 6.5 months)
Number of Participants by Highest Grade Adverse Event Reported
Time Frame: From randomization to last follow-up: weekly during RT, RT end, from end of RT: months 1, (Cetuximab: 2, 3,) 4, 8, 12, 18, 24, 30, 36, then annually. Additionally, prior to each adjuvant durvalumab cycle. Maximum follow-up at time of analysis= 4.2 yr.
Common Terminology Criteria for Adverse Events (version 5.0) grades adverse event severity from 1=mild to 5=death. Summary data is provided in this outcome measure; see Adverse Events Module for specific adverse event data.
From randomization to last follow-up: weekly during RT, RT end, from end of RT: months 1, (Cetuximab: 2, 3,) 4, 8, 12, 18, 24, 30, 36, then annually. Additionally, prior to each adjuvant durvalumab cycle. Maximum follow-up at time of analysis= 4.2 yr.
Change in Quality of Life (QOL) Analysis
Time Frame: Baseline up to 12 months
Assessed using European Organization for Research and Treatment of Cancer Core Questionnaire (EORTC QLQ)/Head-and-Neck module (H&N35), EuroQol- 5 Dimension (EQ5D), M. D. Anderson Dysphagia Inventory (MDADI), patient reported outcomes (PRO)-CTCAE, geriatric screening (G8). The mean summary score of the EORTC QLQ/H&N35, EQ5D, MDADI, PRO-CTCAE, G8, CCI, and the subscales will be determined. The mean change from baseline at each time point will be summarized using mean and standard deviations for each arm. Mean change from baseline will be compared between the arms using a two sample t test. If data normality assumptions are not met, the Wilcoxon rank sum test will be used to test the hypothesis. Mean change from baseline will be tested using an omnibus F test followed by individual comparisons of change scores at different time points within each treatment group. The same analysis will be conducted for between group comparisons at each time point.
Baseline up to 12 months
Change in Swallowing QOL Using Total Composite M. D. Anderson Dysphagia Inventory (MDADI) Score
Time Frame: Baseline up to 1 year
The mean change from baseline at each time point will be summarized using mean and standard deviations for each arm. Mean change from baseline will be compared between the arms using a two sample t test. If data normality assumptions are not met, the Wilcoxon rank sum test will be used to test the hypothesis.
Baseline up to 1 year
Progression-free Survival (Percentage of Participants Alive Without Progression) by Baseline PD-L1 (Programmed Cell Death Ligand 1) Expression
Time Frame: From randomization to date of progression or last follow-up, whichever occurs first. Maximum follow-up at time of analysis was 4.2 years. Two-year PFS estimates are reported.
Failure for progression-free survival is defined as local, regional, or distant disease progression, or death from any cause. Progression was assessed by imaging, clinical assessment, or biopsy. Failure time is defined as time from randomization to failure or last follow-up (censored). PD-L1 expression is defined by a combined positive score (CPS) ≥ 1, assessed by masked central analysis of baseline tissue specimens. CPS = [(number of tumor cells positive for PD-L1) / (number of tumor cells positive for PD-L1 + number of tumor cells negative for PD-L1)] multiplied by 100, yielding a possible score of 0 to 100. Treatment effect hazard ratios within PD-L1 subgroup were estimated by Cox proportional hazards model and progression-free survival estimates were estimated by Kaplan-Meier method. Analysis was planned to occur after 69 failure events had been reported and tissue specimen analysis was complete.
From randomization to date of progression or last follow-up, whichever occurs first. Maximum follow-up at time of analysis was 4.2 years. Two-year PFS estimates are reported.
Progression-free Survival (Percentage of Participants Alive Without Progression) by Baseline p16 Status
Time Frame: From randomization to date of progression or last follow-up, whichever occurs first. Maximum follow-up at time of analysis was 4.2 years. Two-year PFS estimates are reported.
Failure for progression-free survival is defined as local, regional, or distant disease progression, or death from any cause. Progression was assessed by imaging, clinical assessment, or biopsy. Failure time is defined as time from randomization to failure or last follow-up (censored). Positive p16 status was defined as more than 70% strong nuclear or nuclear and cytoplasmic staining of tumor cells, confirmed by central pathology review. Treatment effect hazard ratios within p16 subgroup were estimated by Cox proportional hazards model and progression-free survival estimates were estimated by Kaplan-Meier method. Analysis was planned to occur after 69 failure events had been reported and tissue specimen analysis was complete.
From randomization to date of progression or last follow-up, whichever occurs first. Maximum follow-up at time of analysis was 4.2 years. Two-year PFS estimates are reported.

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Patient Reported Outcomes-Common Terminology Criteria for Adverse Events (PRO-CTCAE)
Time Frame: Up to 3 years
PRO-CTCAE is not intended for expedited reporting, real time review or safety reporting. PRO-CTCAE data are exploratory and not currently intended for use in data safety monitoring or adverse event stopping rules.
Up to 3 years
Secondary Biomarker Analysis
Time Frame: Baseline up to 4 months after RT
Will perform multiparametric flow cytometry on peripheral mononuclear cells (PBMC) from patient-derived blood samples to quantify changes in immune cell frequency and activation status before, during and after radiation combined with cetuximab or radiation combined with durvalumab. To assess the statistical significance of pre- to post-treatment changes in levels of immunoglobulin (Ig)Gs as well as other markers, normalized signal intensities (log2) will be tested using a paired t test within an arm and two sample t test between the two arms. If the distribution assumption is violated for the t tests, nonparametric tests, such as the Wilcoxon signed-rank test will be considered. Lastly, the association between PFS and OS and post-treatment changes in frequency and activation state of T-cells, clonality and diversity of T cell receptor (TCR), and IgG levels will be evaluated using a two-sided Wald test at 0.05 level on the basis of Cox models.
Baseline up to 4 months after RT
QOL Endpoints Using Other Items in EORTC QLQ/HN35, EQ5D and MDADI Subscales
Time Frame: Up to 12-24 months from end of RT
The mean change from baseline at each time point will be summarized using mean and standard deviations for each arm. Mean change from baseline will be compared between the arms using a two sample t test. If data normality assumptions are not met, the Wilcoxon rank sum test will be used to test the hypothesis. Mean change from baseline will be tested using an omnibus F test followed by individual comparisons of change scores at different time points within each treatment group. The same analysis will be conducted for between group comparisons at each time point.
Up to 12-24 months from end of RT

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
National Cancer Institute (NCI)

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
NRG Oncology
Canadian Cancer Trials Group

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Loren K Mell, NRG Oncology

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
April 3, 2018

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
September 20, 2022

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
September 4, 2025

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
August 22, 2017

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 22, 2017

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
August 23, 2017

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
June 2, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 29, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
May 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • NCI-2017-01522 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
  • U10CA180868 (U.S. NIH Grant/Contract)
  • NRG-HN004 (Other Identifier: CTEP)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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Sponsors and Collaborators

Medical Conditions

Drug Interventions

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

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