AzTrials
AzTrials

Clinical Stage III HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8Phase 2/3NCT03258554

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

A Phase 2/3 study testing Cetuximab, Durvalumab and Intensity-Modulated Radiation Therapy in people with Clinical Stage III HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8 and Head and Neck Squamous Cell Carcinoma, run by National Cancer Institute (NCI) at 256 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Cetuximab, Durvalumab and Intensity-Modulated Radiation Therapy
Could I receive a placebo?
No, everyone receives an active treatment
How many people
196 participants
Where
256 sitesin 2 countries
Study dates
3 Apr 2018to 4 Sep 2025
Phase
Phase 2/3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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

Who cannot join

  • 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
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  • 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)

Trial locations and contacts

256 sites in 2 countries.

256 sites in 2 countries

United States252 sites

  • Jefferson Abington Hospital

    Abington, Pennsylvania, 19001

  • Atrium Health Stanly/LCI-Albemarle

    Albemarle, North Carolina, 28002

  • University of New Mexico Cancer Center

    Albuquerque, New Mexico, 87106

  • New Mexico Oncology Hematology Consultants

    Albuquerque, New Mexico, 87109

  • Trinity Health Saint Joseph Mercy Hospital Ann Arbor

    Ann Arbor, Michigan, 48106

  • University of Michigan Comprehensive Cancer Center

    Ann Arbor, Michigan, 48109

  • Langlade Hospital and Cancer Center

    Antigo, Wisconsin, 54409

  • Kaiser Permanente-Deer Valley Medical Center

    Antioch, California, 94531

  • Grady Health System

    Atlanta, Georgia, 30303

  • Emory University Hospital Midtown

    Atlanta, Georgia, 30308

  • Emory University Hospital/Winship Cancer Institute

    Atlanta, Georgia, 30322

  • Sutter Cancer Centers Radiation Oncology Services-Auburn

    Auburn, California, 95603

  • Augusta University Medical Center

    Augusta, Georgia, 30912

  • UCHealth University of Colorado Hospital

    Aurora, Colorado, 80045

  • Greater Baltimore Medical Center

    Baltimore, Maryland, 21204

  • Memorial Sloan Kettering Basking Ridge

    Basking Ridge, New Jersey, 07920

  • McLaren Cancer Institute-Bay City

    Bay City, Michigan, 48706

  • Sanford Joe Lueken Cancer Center

    Bemidji, Minnesota, 56601

  • Alta Bates Summit Medical Center-Herrick Campus

    Berkeley, California, 94704

  • Billings Clinic Cancer Center

    Billings, Montana, 59101

  • University of Alabama at Birmingham Cancer Center

    Birmingham, Alabama, 35233

  • Boston Medical Center

    Boston, Massachusetts, 02118

  • Trinity Health Medical Center - Brighton

    Brighton, Michigan, 48114

  • Crozer-Keystone Regional Cancer Center at Broomall

    Broomall, Pennsylvania, 19008

  • Henry Ford Cancer Institute-Downriver

    Brownstown, Michigan, 48183

  • Roswell Park Cancer Institute

    Buffalo, New York, 14263

  • Lahey Hospital and Medical Center

    Burlington, Massachusetts, 01805

  • Fairview Ridges Hospital

    Burnsville, Minnesota, 55337

  • Saint Alphonsus Cancer Care Center-Caldwell

    Caldwell, Idaho, 83605

  • Trinity Health Medical Center - Canton

    Canton, Michigan, 48188

  • Cleveland Clinic Mercy Hospital

    Canton, Ohio, 44708

  • Aultman Health Foundation

    Canton, Ohio, 44710

  • Saint Francis Medical Center

    Cape Girardeau, Missouri, 63703

  • IU Health North Hospital

    Carmel, Indiana, 46032

  • Christiana Care Health System-Concord Health Center

    Chadds Ford, Pennsylvania, 19317

  • UNC Lineberger Comprehensive Cancer Center

    Chapel Hill, North Carolina, 27599

  • Geauga Hospital

    Chardon, Ohio, 44024

  • Medical University of South Carolina

    Charleston, South Carolina, 29425

  • Carolinas Medical Center/Levine Cancer Institute

    Charlotte, North Carolina, 28203

  • Atrium Health Pineville/LCI-Pineville

    Charlotte, North Carolina, 28210

  • University of Virginia Cancer Center

    Charlottesville, Virginia, 22908

  • Chelsea Hospital

    Chelsea, Michigan, 48118

  • Northwestern University

    Chicago, Illinois, 60611

  • John H Stroger Jr Hospital of Cook County

    Chicago, Illinois, 60612

  • Rush University Medical Center

    Chicago, Illinois, 60612

  • University of Illinois

    Chicago, Illinois, 60612

  • University of Cincinnati Cancer Center-UC Medical Center

    Cincinnati, Ohio, 45219

  • Siteman Cancer Center at Saint Peters Hospital

    City of Saint Peters, Missouri, 63376

  • McLaren Cancer Institute-Clarkston

    Clarkston, Michigan, 48346

  • Case Western Reserve University

    Cleveland, Ohio, 44106

  • MetroHealth Medical Center

    Cleveland, Ohio, 44109

  • Cleveland Clinic Foundation

    Cleveland, Ohio, 44195

  • Henry Ford Macomb Hospital-Clinton Township

    Clinton Township, Michigan, 48038

  • Mercy Cancer Center-West Lakes

    Clive, Iowa, 50325

  • Penrose-Saint Francis Healthcare

    Colorado Springs, Colorado, 80907

  • UCHealth Memorial Hospital Central

    Colorado Springs, Colorado, 80909

  • Memorial Hospital North

    Colorado Springs, Colorado, 80920

  • Ohio State University Comprehensive Cancer Center

    Columbus, Ohio, 43210

  • Memorial Sloan Kettering Commack

    Commack, New York, 11725

  • Atrium Health Cabarrus/LCI-Concord

    Concord, North Carolina, 28025

  • UM Sylvester Comprehensive Cancer Center at Coral Gables

    Coral Gables, Florida, 33146

  • Good Samaritan Hospital

    Corvallis, Oregon, 97330

  • Siteman Cancer Center at West County Hospital

    Creve Coeur, Missouri, 63141

  • Geisinger Medical Center

    Danville, Pennsylvania, 17822

  • Decatur Memorial Hospital

    Decatur, Illinois, 62526

  • UM Sylvester Comprehensive Cancer Center at Deerfield Beach

    Deerfield Beach, Florida, 33442

  • Iowa Methodist Medical Center

    Des Moines, Iowa, 50309

  • Mercy Medical Center - Des Moines

    Des Moines, Iowa, 50314

  • Wayne State University/Karmanos Cancer Institute

    Detroit, Michigan, 48201

  • Henry Ford Hospital

    Detroit, Michigan, 48202

  • City of Hope Comprehensive Cancer Center

    Duarte, California, 91010

  • Kaiser Permanente Dublin

    Dublin, California, 94568

  • Miller-Dwan Hospital

    Duluth, Minnesota, 55805

  • Fairview Southdale Hospital

    Edina, Minnesota, 55435

  • Crossroads Cancer Center

    Effingham, Illinois, 62401

  • Sanford Roger Maris Cancer Center

    Fargo, North Dakota, 58122

  • Weisberg Cancer Treatment Center

    Farmington Hills, Michigan, 48334

  • McLaren Cancer Institute-Flint

    Flint, Michigan, 48532

  • Singh and Arora Hematology Oncology PC

    Flint, Michigan, 48532

  • Poudre Valley Hospital

    Fort Collins, Colorado, 80524

  • Parkview Hospital Randallia

    Fort Wayne, Indiana, 46805

  • Parkview Regional Medical Center

    Fort Wayne, Indiana, 46845

  • Kaiser Permanente-Fremont

    Fremont, California, 94538

  • Fresno Cancer Center

    Fresno, California, 93720

  • Kaiser Permanente-Fresno

    Fresno, California, 93720

  • Unity Hospital

    Fridley, Minnesota, 55432

  • Western Illinois Cancer Treatment Center

    Galesburg, Illinois, 61401

  • Banner MD Anderson Cancer Center

    Gilbert, Arizona, 85234

  • CTCA at Western Regional Medical Center

    Goodyear, Arizona, 85338

  • Nebraska Cancer Specialists/Oncology Hematology West PC

    Grand Island, Nebraska, 68803

  • Saint Vincent Hospital Cancer Center Green Bay

    Green Bay, Wisconsin, 54301

  • Saint Vincent Hospital Cancer Center at Saint Mary's

    Green Bay, Wisconsin, 54303

  • Aurora BayCare Medical Center

    Green Bay, Wisconsin, 54311

  • Gibbs Cancer Center-Pelham

    Greer, South Carolina, 29651

  • Hackensack University Medical Center

    Hackensack, New Jersey, 07601

  • Smilow Cancer Hospital-Hamden Care Center

    Hamden, Connecticut, 06518

  • Memorial Sloan Kettering Westchester

    Harrison, New York, 10604

  • Margaret R Pardee Memorial Hospital

    Hendersonville, North Carolina, 28791

  • Penn State Milton S Hershey Medical Center

    Hershey, Pennsylvania, 17033-0850

  • Hawaii Cancer Care Inc - Waterfront Plaza

    Honolulu, Hawaii, 96813

  • Queen's Medical Center

    Honolulu, Hawaii, 96813

  • The Cancer Center of Hawaii-Liliha

    Honolulu, Hawaii, 96817

  • M D Anderson Cancer Center

    Houston, Texas, 77030

  • Indiana University/Melvin and Bren Simon Cancer Center

    Indianapolis, Indiana, 46202

  • Sidney and Lois Eskenazi Hospital

    Indianapolis, Indiana, 46202

  • Community Cancer Center East

    Indianapolis, Indiana, 46219

  • Community Cancer Center South

    Indianapolis, Indiana, 46227

  • Community Cancer Center North

    Indianapolis, Indiana, 46256

  • Allegiance Health

    Jackson, Michigan, 49201

  • Baptist MD Anderson Cancer Center

    Jacksonville, Florida, 32207

  • University of Wisconsin Carbone Cancer Center - Johnson Creek

    Johnson Creek, Wisconsin, 53038

  • Logan Health Medical Center

    Kalispell, Montana, 59901

  • University of Kansas Cancer Center

    Kansas City, Kansas, 66160

  • Aurora Cancer Care-Kenosha South

    Kenosha, Wisconsin, 53142

  • Gundersen Lutheran Medical Center

    La Crosse, Wisconsin, 54601

  • UC San Diego Moores Cancer Center

    La Jolla, California, 92093

  • Karmanos Cancer Institute at McLaren Greater Lansing

    Lansing, Michigan, 48910

  • Mid-Michigan Physicians-Lansing

    Lansing, Michigan, 48912

  • University of Michigan Health - Sparrow Lansing

    Lansing, Michigan, 48912

  • McLaren Cancer Institute-Lapeer Region

    Lapeer, Michigan, 48446

  • Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center

    Lebanon, New Hampshire, 03756

  • Geisinger Medical Oncology-Lewisburg

    Lewisburg, Pennsylvania, 17837

  • Lewistown Hospital

    Lewistown, Pennsylvania, 17044

  • University of Kentucky/Markey Cancer Center

    Lexington, Kentucky, 40536

  • Cedars Sinai Medical Center

    Los Angeles, California, 90048

  • Norton Hospital Pavilion and Medical Campus

    Louisville, Kentucky, 40202

  • The James Graham Brown Cancer Center at University of Louisville

    Louisville, Kentucky, 40202

  • Norton Brownsboro Hospital and Medical Campus

    Louisville, Kentucky, 40241

  • Banner McKee Medical Center

    Loveland, Colorado, 80539

  • University of Wisconsin Carbone Cancer Center - University Hospital

    Madison, Wisconsin, 53792

  • Cleveland Clinic Cancer Center Mansfield

    Mansfield, Ohio, 44906

  • Aurora Bay Area Medical Group-Marinette

    Marinette, Wisconsin, 54143

  • Froedtert Menomonee Falls Hospital

    Menomonee Falls, Wisconsin, 53051

  • UH Seidman Cancer Center at Lake Health Mentor Campus

    Mentor, Ohio, 44060

  • East Jefferson General Hospital

    Metairie, Louisiana, 70006

  • University of Miami Miller School of Medicine-Sylvester Cancer Center

    Miami, Florida, 33136

  • Memorial Sloan Kettering Monmouth

    Middletown, New Jersey, 07748

  • Beebe South Coastal Health Campus

    Millville, Delaware, 19967

  • Aurora Saint Luke's Medical Center

    Milwaukee, Wisconsin, 53215

  • Medical College of Wisconsin

    Milwaukee, Wisconsin, 53226

  • Zablocki Veterans Administration Medical Center

    Milwaukee, Wisconsin, 53295

  • Hennepin County Medical Center

    Minneapolis, Minnesota, 55415

  • University of South Alabama Mitchell Cancer Institute

    Mobile, Alabama, 36688

  • Kaiser Permanente-Modesto

    Modesto, California, 95356

  • Atrium Health Union/LCI-Union

    Monroe, North Carolina, 28112

  • Forbes Hospital

    Monroeville, Pennsylvania, 15146

  • Memorial Sloan Kettering Bergen

    Montvale, New Jersey, 07645

  • West Virginia University Healthcare

    Morgantown, West Virginia, 26506

  • McLaren Cancer Institute-Macomb

    Mount Clemens, Michigan, 48043

  • ProHealth D N Greenwald Center

    Mukwonago, Wisconsin, 53149

  • Saint Alphonsus Cancer Care Center-Nampa

    Nampa, Idaho, 83687

  • Yale University

    New Haven, Connecticut, 06520

  • Laura and Isaac Perlmutter Cancer Center at NYU Langone

    New York, New York, 10016

  • NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center

    New York, New York, 10032

  • Memorial Sloan Kettering Cancer Center

    New York, New York, 10065

  • Helen F Graham Cancer Center

    Newark, Delaware, 19713

  • Sentara Norfolk General Hospital

    Norfolk, Virginia, 23507

  • Kaiser Permanente Oakland-Broadway

    Oakland, California, 94611

  • Kaiser Permanente-Oakland

    Oakland, California, 94611

  • ProHealth Oconomowoc Memorial Hospital

    Oconomowoc, Wisconsin, 53066

  • University of Oklahoma Health Sciences Center

    Oklahoma City, Oklahoma, 73104

  • University of Kansas Cancer Center-Overland Park

    Overland Park, Kansas, 66210

  • Stanford Cancer Institute Palo Alto

    Palo Alto, California, 94304

  • VA Palo Alto Health Care System

    Palo Alto, California, 94304

  • Methodist Medical Center of Illinois

    Peoria, Illinois, 61636

  • OSF Saint Francis Medical Center

    Peoria, Illinois, 61637

  • McLaren Cancer Institute-Northern Michigan

    Petoskey, Michigan, 49770

  • Fox Chase Cancer Center

    Philadelphia, Pennsylvania, 19111

  • Temple University Hospital

    Philadelphia, Pennsylvania, 19140

  • Allegheny General Hospital

    Pittsburgh, Pennsylvania, 15212

  • UPMC-Shadyside Hospital

    Pittsburgh, Pennsylvania, 15232

  • McLaren-Port Huron

    Port Huron, Michigan, 48060

  • Providence Portland Medical Center

    Portland, Oregon, 97213

  • Providence Saint Vincent Medical Center

    Portland, Oregon, 97225

  • Kaiser Permanente Northwest

    Portland, Oregon, 97227

  • Kaiser Permanente-Rancho Cordova Cancer Center

    Rancho Cordova, California, 95670

  • Beebe Health Campus

    Rehoboth Beach, Delaware, 19971

  • Kaiser Permanente-Richmond

    Richmond, California, 94801

  • VCU Massey Cancer Center at Stony Point

    Richmond, Virginia, 23235

  • VCU Massey Comprehensive Cancer Center

    Richmond, Virginia, 23298

  • Mayo Clinic in Rochester

    Rochester, Minnesota, 55905

  • University of Rochester

    Rochester, New York, 14642

  • Rock Hill Radiation Therapy Center

    Rock Hill, South Carolina, 29730

  • Rohnert Park Cancer Center

    Rohnert Park, California, 94928

  • Kaiser Permanente-Roseville

    Roseville, California, 95661

  • Sutter Cancer Centers Radiation Oncology Services-Roseville

    Roseville, California, 95661

  • The Permanente Medical Group-Roseville Radiation Oncology

    Roseville, California, 95678

  • Kaiser Permanente Downtown Commons

    Sacramento, California, 95814

  • Sutter Medical Center Sacramento

    Sacramento, California, 95816

  • University of California Davis Comprehensive Cancer Center

    Sacramento, California, 95817

  • Kaiser Permanente-South Sacramento

    Sacramento, California, 95823

  • South Sacramento Cancer Center

    Sacramento, California, 95823

  • MyMichigan Medical Center Saginaw

    Saginaw, Michigan, 48601

  • Coborn Cancer Center at Saint Cloud Hospital

    Saint Cloud, Minnesota, 56303

  • Dartmouth Cancer Center - North

    Saint Johnsbury, Vermont, 05819

  • Regions Hospital

    Saint Paul, Minnesota, 55101

  • Salina Regional Health Center

    Salina, Kansas, 67401

  • Kaiser Permanente-San Francisco

    San Francisco, California, 94115

  • UCSF Medical Center-Mount Zion

    San Francisco, California, 94115

  • UCSF Medical Center-Mission Bay

    San Francisco, California, 94158

  • Kaiser Permanente-Santa Teresa-San Jose

    San Jose, California, 95119

  • Kaiser Permanente San Leandro

    San Leandro, California, 94577

  • Kaiser San Rafael-Gallinas

    San Rafael, California, 94903

  • North Coast Cancer Care

    Sandusky, Ohio, 44870

  • Kaiser Permanente Medical Center - Santa Clara

    Santa Clara, California, 95051

  • Kaiser Permanente-Santa Rosa

    Santa Rosa, California, 95403

  • Guthrie Medical Group PC-Robert Packer Hospital

    Sayre, Pennsylvania, 18840

  • University of Washington Medical Center - Montlake

    Seattle, Washington, 98195

  • Vince Lombardi Cancer Clinic-Sheboygan

    Sheboygan, Wisconsin, 53081

  • Avera Cancer Institute

    Sioux Falls, South Dakota, 57105

  • Sanford USD Medical Center - Sioux Falls

    Sioux Falls, South Dakota, 57117-5134

  • City of Hope South Pasadena

    South Pasadena, California, 91030

  • Kaiser Permanente Cancer Treatment Center

    South San Francisco, California, 94080

  • Kaiser Permanente-South San Francisco

    South San Francisco, California, 94080

  • Spartanburg Medical Center

    Spartanburg, South Carolina, 29303

  • Springfield Memorial Hospital

    Springfield, Illinois, 62781

  • Washington University School of Medicine

    St Louis, Missouri, 63110

  • Mercy Hospital Saint Louis

    St Louis, Missouri, 63141

  • Kaiser Permanente-Stockton

    Stockton, California, 95210

  • Stony Brook University Medical Center

    Stony Brook, New York, 11794

  • Aurora Medical Center in Summit

    Summit, Wisconsin, 53066

  • ProMedica Flower Hospital

    Sylvania, Ohio, 43560

  • State University of New York Upstate Medical University

    Syracuse, New York, 13210

  • Moffitt Cancer Center

    Tampa, Florida, 33612

  • Montefiore Medical Center - Moses Campus

    The Bronx, New York, 10467

  • James J Peters VA Medical Center

    The Bronx, New York, 10468

  • Torrance Memorial Physician Network - Cancer Care

    Torrance, California, 90505

  • Torrance Memorial Medical Center

    Torrance, California, 90509

  • Gene Upshaw Memorial Tahoe Forest Cancer Center

    Truckee, California, 96161

  • Smilow Cancer Hospital Care Center-Trumbull

    Trumbull, Connecticut, 06611

  • Banner University Medical Center - Tucson

    Tucson, Arizona, 85719

  • University of Arizona Cancer Center-North Campus

    Tucson, Arizona, 85719

  • Memorial Sloan Kettering Nassau

    Uniondale, New York, 11553

  • Carle Cancer Center

    Urbana, Illinois, 61801

  • Kaiser Permanente Medical Center-Vacaville

    Vacaville, California, 95688

  • Kaiser Permanente-Vallejo

    Vallejo, California, 94589

  • Kaiser Permanente-Walnut Creek

    Walnut Creek, California, 94596

  • Smilow Cancer Hospital Care Center - Waterford

    Waterford, Connecticut, 06385

  • UW Cancer Center at ProHealth Care

    Waukesha, Wisconsin, 53188

  • Aspirus Regional Cancer Center

    Wausau, Wisconsin, 54401

  • Aurora West Allis Medical Center

    West Allis, Wisconsin, 53227

  • Froedtert West Bend Hospital/Kraemer Cancer Center

    West Bend, Wisconsin, 53095

  • Henry Ford West Bloomfield Hospital

    West Bloomfield, Michigan, 48322

  • University of Cincinnati Cancer Center-West Chester

    West Chester, Ohio, 45069

  • Reading Hospital

    West Reading, Pennsylvania, 19611

  • UHHS-Westlake Medical Center

    Westlake, Ohio, 44145

  • University of Kansas Hospital-Westwood Cancer Center

    Westwood, Kansas, 66205

  • Wexford Health and Wellness Pavilion

    Wexford, Pennsylvania, 15090

  • Ascension Via Christi Hospitals Wichita

    Wichita, Kansas, 67214

  • Geisinger Wyoming Valley/Henry Cancer Center

    Wilkes-Barre, Pennsylvania, 18711

  • Asplundh Cancer Pavilion

    Willow Grove, Pennsylvania, 19090

  • Cleveland Clinic Wooster Family Health and Surgery Center

    Wooster, Ohio, 44691

Other trials in United States

Canada4 sites

  • London Regional Cancer Program

    London, Ontario, N6A 4L6

  • The Research Institute of the McGill University Health Centre (MUHC)

    Montreal, Quebec, H3H 2R9

  • Allan Blair Cancer Centre

    Regina, Saskatchewan, S4T 7T1

  • University Health Network-Princess Margaret Hospital

    Toronto, Ontario, M5G 2M9

Other trials in Canada

About this study

Official title: 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.

Read the detailed description

PRIMARY OBJECTIVES:

  1. 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:

  1. 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.

  1. 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:

  1. 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.

  1. 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.

Being tested
Cetuximab, Durvalumab, Intensity-Modulated Radiation Therapy, Laboratory Biomarker Analysis, Quality-of-Life Assessment
Medical subject headings
Oropharyngeal Neoplasms, Squamous Cell Carcinoma of Head and Neck, Hypopharyngeal Neoplasms, Laryngeal Neoplasms, Mouth Neoplasms, Carcinoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CetuximabBiological

    Also called C 225, C-225, C225, Cetuximab Biosimilar CDP-1

    Given IV

  • DurvalumabBiological

    Also called Imfinzi, Immunoglobulin G1, Anti-(Human Protein B7-H1) (Human Monoclonal MEDI4736 Heavy Chain), Disulfide with Human Monoclonal MEDI4736 Kappa-chain, Dimer, MEDI 4736, MEDI-4736

    Given IV

  • Intensity-Modulated Radiation TherapyRadiation

    Also called IMRT, Intensity modulated radiation therapy (procedure), Intensity Modulated RT, Intensity-Modulated Radiotherapy

    Undergo IMRT

  • Laboratory Biomarker AnalysisOther

    Correlative studies

  • Quality-of-Life AssessmentOther

    Also called Quality of Life Assessment

    Ancillary studies

  • Questionnaire AdministrationOther

    Ancillary studies

Study groups in NCT03258554
Study groupRoleWhat they receive
Arm I (cetuximab, radiation therapy)Active comparatorPatients 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.
Receives: Biological: Cetuximab; Radiation: Intensity-Modulated Radiation Therapy; Other: Laboratory Biomarker Analysis; Other: Quality-of-Life Assessment; Other: Questionnaire Administration
Arm II (durvalumab, radiation therapy)ExperimentalPatients 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.
Receives: Biological: Durvalumab; Radiation: Intensity-Modulated Radiation Therapy; Other: Laboratory Biomarker Analysis; Other: Quality-of-Life Assessment; Other: Questionnaire Administration

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of Participants With Dose-limiting Toxicity (DLT) [Lead-in Phase]

    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.

    Measured: 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.

  2. Progression-free Survival (Percentage of Participants Alive Without Progression) [Phase II Primary]

    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.

    Measured: 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.

  3. Overall Survival (Percentage of Participants Alive) [Originally Phase III Primary / Now Phase II Secondary]

    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.

    Measured: 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 outcomes (12)

  1. Locoregional Failure (Percentage of Participants With Locoregional Failure)

    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.

    Measured: 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.

  2. Distant Metastasis (Percentage of Participants With Distant Metastasis)

    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.

    Measured: 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.

  3. Competing Mortality (Percentage of Participants Who Died Due to Causes Other Than Study Cancer)

    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.

    Measured: 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.

  4. Percentage of Participants With Complete or Partial Response at 4-month Scan Determined by Response Evaluation Criteria in Solid Tumors (RECIST) v. 1.1

    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

    Measured: Baseline and 4 months after end of RT (approximately 6.5 months)

  5. Number of Participants by Highest Grade Adverse Event Reported

    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.

    Measured: 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.

  6. Change in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ C30) Physical Functioning Score at One Year

    The EORTC QLQ C30 Physical Functioning score measures patient reported limitations in physical activities. Possible scores for each score range from 0 to 100, with higher scores indicating better physical functioning. Change is defined as the time point score minus the baseline score, where positive values indicate improvement for and negative values indicate.

    Measured: Baseline and one year after end of radiation therapy (approximately 7 weeks)

  7. Change in MD Anderson Dysphagia Inventory (MDADI) Composite Score at One Year

    The MDADI Composite score measures overall swallowing related quality of life derived from the emotional, functional, and physical scores, excluding the global item. Possible scores range from 20 to 100, with higher scores indicating better swallowing related quality of life. Change is defined as the time point score minus the baseline score, where positive values indicate improvement and negative values indicate decline.

    Measured: Baseline and one year after end of radiation therapy (approximately 7 weeks)

  8. Change in Performance Status Scale for Head and Neck Cancer (PSS HN) Normalcy of Diet Score at One Year

    The PSS HN Normalcy of Diet score measures clinician rated normalcy of diet. Possible scores range from 0 to 100, with higher scores indicating better dietary function. Change is defined as the time point score minus the baseline score, where positive values indicate improvement and negative values indicate worsening function.

    Measured: Baseline and one year after end of radiation therapy (approximately 7 weeks)

  9. Change in PSS HN Eating in Public Score at One Year

    The PSS HN Eating in Public score measures clinician rated public eating. Possible scores range from 0 to 100, with higher scores indicating better eating function. Change is defined as the time point score minus the baseline score, where positive values indicate improvement and negative values indicate worsening function.

    Measured: Baseline and one year after end of radiation therapy (approximately 7 weeks)

  10. Change in PSS HN Understandability of Speech Score at One Year

    The PSS HN Understandability of Speech score measures clinician rated speech. Possible scores range from 0 to 100, with higher scores indicating better speech function. Change is defined as the time point score minus the baseline score, where positive values indicate improvement and negative values indicate worsening function.

    Measured: Baseline and one year after end of radiation therapy (approximately 7 weeks)

  11. Progression-free Survival (Percentage of Participants Alive Without Progression) by Baseline PD-L1 (Programmed Cell Death Ligand 1) Expression

    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.

    Measured: 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.

  12. Progression-free Survival (Percentage of Participants Alive Without Progression) by Baseline p16 Status

    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.

    Measured: 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.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted23 Aug 2017
  2. Study start3 Apr 2018
  3. Primary completion20 Sep 2022
  4. Study completion4 Sep 2025

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2/3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
196 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03258554
Sponsor's protocol ID
NCI-2017-01522
Other IDs
NCI-2017-01522, NRG-HN004, NRG-HN004, U10CA180868
Status last verified
Aug 2026
First submitted
22 Aug 2017
Last updated
27 Aug 2026
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • Mell LK, Torres-Saavedra PA, Wong SJ, Kish JA, Chang SS, Jordan RC, Liu T, Truong MT, Winquist EW, Takiar V, Wise-Draper T, Robbins JR, Rodriguez CP, Awan MJ, Beadle BM, Henson C, Narayan S, Spencer SA, Powell S, Dunlap N, Sacco AG, Hu KS, Park HS, Bauman JE, Harris J, Yom SS, Le QT. Radiotherapy with cetuximab or durvalumab for locoregionally advanced head and neck cancer in patients with a contraindication to cisplatin (NRG-HN004): an open-label, multicentre, parallel-group, randomised, phase 2/3 trial. Lancet Oncol. 2024 Dec;25(12):1576-1588. doi: 10.1016/S1470-2045(24)00507-2. Epub 2024 Nov 14.

    PubMed 39551064

Questions about this trial

What is this clinical trial studying?

A Phase 2/3 study testing Cetuximab, Durvalumab and Intensity-Modulated Radiation Therapy in people with Clinical Stage III HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8 and Head and Neck Squamous Cell Carcinoma, run by National Cancer Institute (NCI) at 256 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 46 inclusion and 45 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 27 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 256 sites in United States, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 25 Oct 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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.). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03258554, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Aug 2026.

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