AzTrials
AzTrials

Basaloid Squamous Cell CarcinomaPhase 2/3NCT03952585

De-intensified Radiation Therapy With Chemotherapy (Cisplatin) or Immunotherapy (Nivolumab) in Treating Patients With Early-Stage, HPV-Positive, Non-Smoking Associated Oropharyngeal Cancer

A Phase 2/3 study testing Biopsy Procedure, Biospecimen Collection and Cisplatin in people with Basaloid Squamous Cell Carcinoma and Clinical Stage I HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8, run by National Cancer Institute (NCI) at 494 sites in 2 countries.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial summary

This phase II/III trial studies how well a reduced dose of radiation therapy works with nivolumab compared to cisplatin in treating patients with human papillomavirus (HPV)-positive oropharyngeal cancer that is early in its growth and may not have spread to other parts of the body (early-stage), and is not associated… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Biopsy Procedure, Biospecimen Collection and Cisplatin
Could I receive a placebo?
No, everyone receives an active treatment
How many people
384 participants
Where
494 sitesin 2 countries
Study dates
9 Oct 2019to 11 Dec 2026
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

  • Pathologically (histologically or cytologically) proven diagnosis of squamous cell carcinoma (including the histological variants papillary squamous cell carcinoma and basaloid squamous cell carcinoma but not neuroendocrine phenotype) of the oropharynx (tonsil, base of tongue, soft palate, or oropharyngeal walls); cytologic diagnosis from a cervical lymph node is sufficient in the presence of clinical evidence of a primary tumor in the oropharynx. Clinical evidence should be documented, may consist of palpation, imaging, or endoscopic evaluation, and should be sufficient to estimate the size of the primary (for T stage)
  • Patients must have clinically or radiographically evident measurable disease at the primary site or at nodal stations. Simple tonsillectomy or local excision of the primary without removal of nodal disease is permitted, as is excision removing gross nodal disease but with intact primary site. Limited neck dissections retrieving =< 4 nodes are permitted and considered as non-therapeutic nodal excisions
  • P16-positive based on local site immunohistochemical tissue staining (defined as greater than 70% strong diffuse nuclear or nuclear and cytoplasmic staining of tumor cells). Fine needle aspiration (FNA) biopsy specimens may be used as the sole diagnostic tissue. Centers are encouraged to contact the pathology chair for clarification
  • Note: Institutions must screen patients, whose tumors must be p16-positive by immunohistochemistry (IHC) in order to be eligible for the trial using a Clinical Laboratory Improvement Amendments (CLIA)-certified laboratory. A rigorous laboratory accreditation process similar to the United States (U.S.) CLIA certification, such as the provincial accreditation status offered by the Ontario Laboratory Accreditation (OLA) Program in Canada, the College of American Pathologists (CAP), or an equivalent accreditation in other countries, is acceptable. The p16-positive results must be reported on the pathology report being submitted
  • Note: If p16 result is equivocal, positive HPV deoxyribonucleic acid (DNA) test of tumor specimen is acceptable and fulfills the eligibility criteria
  • Clinical stage T1-2, N1, M0 (American Joint Committee on Cancer [AJCC], 8th edition [ed.]) or T3, N0-N1, M0 (AJCC, 8th ed.) including no distant metastases based on the following diagnostic workup:
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  • General history and physical examination within 56 days prior to registration;
  • Exam with laryngopharyngoscopy (mirror or in office direct procedure acceptable) within 70 days prior to registration;
  • One of the following imaging studies is required within 56 days prior to registration:
  • FDG-PET/CT of the neck and chest (with or without contrast); FDG-PET/CT scan is strongly preferred and highly recommended to be used for eligibility OR
  • Chest CT (with or without contrast)
  • One of the following imaging studies is required within 28 days prior to registration:
  • A diagnostic CT scan of neck (with contrast and of diagnostic quality) OR
  • An magnetic resonance imaging (MRI) of the neck (with contrast and of diagnostic quality)
  • Note: A diagnostic quality CT or MRI with contrast or FDG-PET/CT scan of neck performed for the purposes of radiation planning may serve as both staging and planning tools
  • Patients must provide their personal smoking history prior to registration. The lifetime cumulative history cannot exceed 10 pack-years. The following formula is used to calculate the pack-years during the periods of smoking in the patient's life; the cumulative total of the number of pack-years during each period of active smoking is the lifetime cumulative history
  • Number of pack-years = [Frequency of smoking (number of cigarettes per day) x duration of cigarette smoking (years)] / 20
  • Note: Twenty cigarettes is considered equivalent to one pack. The effect of non-cigarette tobacco products on the survival of patients with p16-positive oropharyngeal cancers is undefined. While there are reportedly increased risks of head and neck cancer associated with sustained heavy cigar and pipe use (Wyss 2013), such sustained use of non-cigarette products is unusual and does not appear to convey added risk with synchronous cigarette smoking. Cigar and pipe tobacco consumption is therefore not included in calculating the lifetime pack-years. Marijuana consumption is likewise not considered in this calculation. There is no clear scientific evidence regarding the role of chewing tobacco-containing products in this disease, although this is possibly more concerning given the proximity of the oral cavity and oropharynx. In any case, investigators are discouraged from enrolling patients with a history of very sustained use (such as several years or more) of non-cigarette tobacco products alone
  • Zubrod performance status of 0-1 within 14 days prior to registration
  • Age >= 18
  • Absolute neutrophil count >= 1,500/mcL (within 14 days prior to registration)
  • Platelets >= 100,000/mcL (within 14 days prior to registration)
  • Hemoglobin >= 8.0 g/dL (within 14 days prior to registration) (Note: use of transfusion or other intervention to achieve hemoglobin [Hgb] >= 8.0 g/dL is acceptable)
  • Total bilirubin =< 1.5 x institutional upper limit of normal (ULN) (within 14 days prior to registration)
  • Aspartate aminotransferase (AST)(serum glutamic-oxaloacetic transaminase [SGOT]) or alanine aminotransferase (ALT)(serum glutamate pyruvate transaminase [SGPT]) =< 3.0 x institutional ULN (within 14 days prior to registration)
  • Serum creatinine =< 1.5 x ULN OR creatinine clearance (CrCl) >= 50 mL/min (if using the Cockcroft-Gault formula) (within 14 days prior to registration)
  • Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
  • For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
  • Note: Known positive test for hepatitis B virus surface antigen (HBV sAg) indicating acute or chronic infection would make the patient ineligible unless the viral load becomes undetectable on suppressive therapy. Patients who are immune to hepatitis B (anti-hepatitis B surface antibody positive) are eligible (e.g. patients immunized against hepatitis B)
  • Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment for the hepatitis, they are eligible if they have an undetectable HCV viral load.
  • Note: Known positive test for hepatitis C virus ribonucleic acid (HCV RNA) indicating acute or chronic infection would make the patient ineligible unless the viral load becomes undetectable on suppressive therapy
  • For women of childbearing potential (WOCBP), negative serum or urine pregnancy test within 24 hours prior to registration
  • Women of childbearing potential (WOCBP) is defined as any female who has experienced menarche and who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy) or who is not postmenopausal. Menopause is defined clinically as 12 months of amenorrhea in a woman over 45 in the absence of other biological or physiological causes. In addition, women under the age of 55 must have a documented serum follicle stimulating hormone (FSH) level less than 40 mIU/mL
  • Women of childbearing potential (WOCBP) and men who are sexually active with WOCBP must be willing to use an adequate method of contraception during and after treatment
  • The patient or a legally authorized representative must provide study-specific informed consent prior to study entry
  • Only English, Spanish, or French speaking patients are eligible to participate as these are the only languages for which the mandatory dysphagia-related patient reported instrument (MDADI) is available

Who cannot join

  • Clinical stages T0; T4; T1-2, N0; or any N2 (AJCC, 8th ed)
  • Recurrent disease
  • Definitive clinical or radiologic evidence of metastatic disease or adenopathy below the clavicles
  • Cancers considered to be from an oral cavity site (oral tongue, floor mouth, alveolar ridge, buccal or lip), or the nasopharynx, hypopharynx, or larynx, even if p16-positive, or histologies of adenosquamous, verrucous, or spindle cell carcinomas
  • Carcinoma of the neck of unknown primary site origin (T0 is ineligible, even if p16-positive)
  • Radiographically matted nodes, defined as 3 abutting nodes with loss of the intervening fat plane
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  • Supraclavicular nodes, defined as nodes centered below the level of the cricoid cartilage
  • Gross total excision of both primary and nodal disease; this includes tonsillectomy, local excision of primary site, and nodal excision that removes all clinically and radiographically evident disease. In other words, to participate in this protocol, the patient must have clinically or radiographically evident gross disease for which disease response can be assessed
  • Patients with simultaneous primary cancers or separate bilateral primary tumor sites are excluded with the exception of patients with bilateral tonsil cancers
  • Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for a minimum of 1095 days (3 years) (of note, the exclusion applies only for invasive cancers such that carcinoma in situ of the breast, oral cavity, or cervix are all permissible)
  • Prior systemic chemotherapy for the study cancer; note that prior chemotherapy for a different cancer is allowable
  • Prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields
  • Prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways
  • History of severe hypersensitivity reaction to any monoclonal antibody.
  • Severe, active co-morbidity defined as follows:
  • Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months
  • Transmural myocardial infarction within the last 6 months
  • Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration
  • Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy within 30 days of registration
  • Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects
  • Acquired immune deficiency syndrome (AIDS) based upon current Centers for Disease Control and Prevention (CDC) definition with immune compromise greater than that noted; note, however, that HIV testing is not required for entry into this protocol. The need to exclude patients with AIDS from this protocol is necessary because the treatments involved in this protocol may be significantly immunosuppressive. Protocol-specific requirements may also exclude immuno-compromised patients
  • Condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of registration. Inhaled or topical steroids and adrenal replacement doses < 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease
  • Patients with active autoimmune disease requiring systemic treatment (i.e. disease modifying agents, corticosteroids, or immunosuppressive drugs) should be excluded. These include but are not limited to patients with a history of immune related neurologic disease, multiple sclerosis, autoimmune (demyelinating) neuropathy, Guillain-Barre syndrome, myasthenia gravis; systemic autoimmune disease such as systemic lupus erythematosus (SLE), rheumatoid arthritis, connective tissue diseases, scleroderma, inflammatory bowel disease (IBD), Crohn's, ulcerative colitis, hepatitis; and patients with a history of toxic epidermal necrolysis (TEN), Stevens-Johnson syndrome, or phospholipid syndrome should be excluded because of the risk of recurrence or exacerbation of disease
  • Note: Patients are permitted to enroll if they have vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger (precipitating event)
  • Patients who are pregnant, nursing, or expecting to conceive or father children
  • Prior allergic reaction to cisplatin

Trial locations and contacts

494 sites in 2 countries.

301 sites in 2 countries

United States300 sites

  • Hawaii Cancer Care - Westridge

    ‘Aiea, Hawaii, 96701

  • Pali Momi Medical Center

    ‘Aiea, Hawaii, 96701

  • Summa Health System - Akron Campus

    Akron, Ohio, 44304

  • University of New Mexico Cancer Center

    Albuquerque, New Mexico, 87106

  • New Mexico Oncology Hematology Consultants

    Albuquerque, New Mexico, 87109

  • Lehigh Valley Hospital-Cedar Crest

    Allentown, Pennsylvania, 18103

  • UPMC Altoona

    Altoona, Pennsylvania, 16601

  • The Don and Sybil Harrington Cancer Center

    Amarillo, Texas, 79106

  • American Fork Hospital / Huntsman Intermountain Cancer Center

    American Fork, Utah, 84003

  • Trinity Health Saint Joseph Mercy Hospital Ann Arbor

    Ann Arbor, Michigan, 48106

  • Aspirus Cancer Care-Antigo-Volm Cancer Center

    Antigo, Wisconsin, 54409

  • Kaiser Permanente-Deer Valley Medical Center

    Antioch, California, 94531

  • Ascension Northeast Wisconsin-Saint Elizabeth Cancer Center-Appleton

    Appleton, Wisconsin, 54915

  • PCR Oncology

    Arroyo Grande, California, 93420

  • Duluth Clinic Ashland

    Ashland, Wisconsin, 54806

  • Northwest Wisconsin Cancer Center

    Ashland, Wisconsin, 54806

  • Grady Health System

    Atlanta, Georgia, 30303

  • Emory University Hospital Midtown

    Atlanta, Georgia, 30308

  • Sutter Auburn Faith Hospital

    Auburn, California, 95602

  • Sutter Cancer Centers Radiation Oncology Services-Auburn

    Auburn, California, 95603

  • Rocky Mountain Regional VA Medical Center

    Aurora, Colorado, 80045

  • UCHealth University of Colorado Hospital

    Aurora, Colorado, 80045

  • Rush-Copley Medical Center

    Aurora, Illinois, 60504

  • UH Seidman Cancer Center at UH Avon Health Center

    Avon, Ohio, 44011

  • AIS Cancer Center at San Joaquin Community Hospital

    Bakersfield, California, 93301

  • University of Maryland/Greenebaum Cancer Center

    Baltimore, Maryland, 21201

  • Greater Baltimore Medical Center

    Baltimore, Maryland, 21204

  • Summa Health System - Barberton Campus

    Barberton, Ohio, 44203

  • Advocate Good Shepherd Hospital

    Barrington, Illinois, 60010

  • MaineHealth Coastal Cancer Treatment Center

    Bath, Maine, 04530

  • LSU Health Baton Rouge-North Clinic

    Baton Rouge, Louisiana, 70805

  • Our Lady of the Lake Physician Group

    Baton Rouge, Louisiana, 70808

  • Louisiana Hematology Oncology Associates LLC

    Baton Rouge, Louisiana, 70809

  • Mary Bird Perkins Cancer Center

    Baton Rouge, Louisiana, 70809

  • McLaren Cancer Institute-Bay City

    Bay City, Michigan, 48706

  • UPMC-Heritage Valley Health System Beaver

    Beaver, Pennsylvania, 15009

  • UM Upper Chesapeake Medical Center

    Bel Air, Maryland, 21014

  • Sanford Joe Lueken Cancer Center

    Bemidji, Minnesota, 56601

  • Tower Cancer Research Foundation

    Beverly Hills, California, 90211

  • MaineHealth Maine Medical Center - Biddeford

    Biddeford, Maine, 04005

  • University of Alabama at Birmingham Cancer Center

    Birmingham, Alabama, 35233

  • Sanford Bismarck Medical Center

    Bismarck, North Dakota, 58501

  • Illinois CancerCare-Bloomington

    Bloomington, Illinois, 61704

  • Saint Alphonsus Cancer Care Center-Boise

    Boise, Idaho, 83706

  • Saint Luke's Cancer Institute - Boise

    Boise, Idaho, 83712

  • Boston Medical Center

    Boston, Massachusetts, 02118

  • Dana-Farber Cancer Institute

    Boston, Massachusetts, 02215

  • Rocky Mountain Cancer Centers-Boulder

    Boulder, Colorado, 80304

  • Bozeman Health Deaconess Hospital

    Bozeman, Montana, 59715

  • Essentia Health Saint Joseph's Medical Center

    Brainerd, Minnesota, 56401

  • Trinity Health IHA Medical Group Hematology Oncology - Brighton

    Brighton, Michigan, 48114

  • Trinity Health Medical Center - Brighton

    Brighton, Michigan, 48114

  • Ascension Southeast Wisconsin Hospital-Elmbrook Campus-Brookfield

    Brookfield, Wisconsin, 53045

  • Henry Ford Cancer Institute-Downriver

    Brownstown, Michigan, 48183

  • Aurora Cancer Care-Southern Lakes VLCC

    Burlington, Wisconsin, 53105

  • Saint Alphonsus Cancer Care Center-Caldwell

    Caldwell, Idaho, 83605

  • Sutter Cancer Centers Radiation Oncology Services-Cameron Park

    Cameron Park, California, 95682

  • Sands Cancer Center

    Canandaigua, New York, 14424

  • Illinois CancerCare-Canton

    Canton, Illinois, 61520

  • Trinity Health IHA Medical Group Hematology Oncology - Canton

    Canton, Michigan, 48188

  • Trinity Health Medical Center - Canton

    Canton, Michigan, 48188

  • Saint Francis Medical Center

    Cape Girardeau, Missouri, 63703

  • Carlisle Regional Cancer Center

    Carlisle, Pennsylvania, 17015

  • IU Health North Hospital

    Carmel, Indiana, 46032

  • Caro Cancer Center

    Caro, Michigan, 48723

  • Illinois CancerCare-Carthage

    Carthage, Illinois, 62321

  • Centralia Oncology Clinic

    Centralia, Illinois, 62801

  • Christiana Care Health System-Concord Health Center

    Chadds Ford, Pennsylvania, 19317

  • Chambersburg Hospital

    Chambersburg, Pennsylvania, 17201

  • Geauga Hospital

    Chardon, Ohio, 44024

  • Medical University of South Carolina

    Charleston, South Carolina, 29425

  • Carolinas Medical Center/Levine Cancer Institute

    Charlotte, North Carolina, 28203

  • Novant Health Presbyterian Medical Center

    Charlotte, North Carolina, 28204

  • Atrium Health Pineville/LCI-Pineville

    Charlotte, North Carolina, 28210

  • Atrium Health University City/LCI-University

    Charlotte, North Carolina, 28262

  • Levine Cancer Institute-Ballantyne

    Charlotte, North Carolina, 28277

  • Chelsea Hospital

    Chelsea, Michigan, 48118

  • Trinity Health IHA Medical Group Hematology Oncology - Chelsea Hospital

    Chelsea, Michigan, 48118

  • Northwestern University

    Chicago, Illinois, 60611

  • Rush MD Anderson Cancer Center

    Chicago, Illinois, 60612

  • Advocate Illinois Masonic Medical Center

    Chicago, Illinois, 60657

  • Ascension Calumet Hospital-Chilton

    Chilton, Wisconsin, 53014

  • University of Cincinnati Cancer Center-UC Medical Center

    Cincinnati, Ohio, 45219

  • Siteman Cancer Center at Saint Peters Hospital

    City of Saint Peters, Missouri, 63376

  • Clackamas Radiation Oncology Center

    Clackamas, Oregon, 97015

  • Providence Cancer Institute Clackamas Clinic

    Clackamas, Oregon, 97015

  • McLaren Cancer Institute-Clarkston

    Clarkston, Michigan, 48346

  • Wake Forest University at Clemmons

    Clemmons, North Carolina, 27012

  • Case Western Reserve University

    Cleveland, Ohio, 44106

  • MetroHealth Medical Center

    Cleveland, Ohio, 44109

  • Cleveland Clinic Cancer Center/Fairview Hospital

    Cleveland, Ohio, 44111

  • Cleveland Clinic Foundation

    Cleveland, Ohio, 44195

  • Henry Ford Macomb Hospital-Clinton Township

    Clinton Township, Michigan, 48038

  • Mercy Cancer Center-West Lakes

    Clive, Iowa, 50325

  • UI Health Care Mission Cancer and Blood - West Des Moines Clinic

    Clive, Iowa, 50325

  • Rocky Mountain Cancer Centers-Penrose

    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

  • Atrium Health Cabarrus/LCI-Concord

    Concord, North Carolina, 28025

  • UM Sylvester Comprehensive Cancer Center at Coral Gables

    Coral Gables, Florida, 33146

  • UM Sylvester Comprehensive Cancer Center at Coral Springs

    Coral Springs, Florida, 33065

  • Greater Regional Medical Center

    Creston, Iowa, 50801

  • Siteman Cancer Center at West County Hospital

    Creve Coeur, Missouri, 63141

  • AMG Crystal Lake - Oncology

    Crystal Lake, Illinois, 60014

  • Noyes Memorial Hospital/Myers Cancer Center

    Dansville, New York, 14437

  • Geisinger Medical Center

    Danville, Pennsylvania, 17822

  • Henry Ford Medical Center-Fairlane

    Dearborn, Michigan, 48126

  • Cancer Care Specialists of Illinois - Decatur

    Decatur, Illinois, 62526

  • Decatur Memorial Hospital

    Decatur, Illinois, 62526

  • Essentia Health - Deer River Clinic

    Deer River, Minnesota, 56636

  • UM Sylvester Comprehensive Cancer Center at Deerfield Beach

    Deerfield Beach, Florida, 33442

  • Northwestern Medicine Cancer Center Kishwaukee

    DeKalb, Illinois, 60115

  • AdventHealth Porter

    Denver, Colorado, 80210

  • Iowa Methodist Medical Center

    Des Moines, Iowa, 50309

  • UI Health Care Mission Cancer and Blood - Des Moines Clinic

    Des Moines, Iowa, 50309

  • Broadlawns Medical Center

    Des Moines, Iowa, 50314

  • Mercy Medical Center - Des Moines

    Des Moines, Iowa, 50314

  • UI Health Care Mission Cancer and Blood - Laurel Clinic

    Des Moines, Iowa, 50314

  • Iowa Lutheran Hospital

    Des Moines, Iowa, 50316

  • Wayne State University/Karmanos Cancer Institute

    Detroit, Michigan, 48201

  • Henry Ford Hospital

    Detroit, Michigan, 48202

  • Advocate Good Samaritan Hospital

    Downers Grove, Illinois, 60515

  • City of Hope Comprehensive Cancer Center

    Duarte, California, 91010

  • Kaiser Permanente Dublin

    Dublin, California, 94568

  • Essentia Health Cancer Center

    Duluth, Minnesota, 55805

  • Essentia Health Saint Mary's Medical Center

    Duluth, Minnesota, 55805

  • Miller-Dwan Hospital

    Duluth, Minnesota, 55805

  • Fox Chase Cancer Center - East Norriton Hospital Outpatient Center

    East Norriton, Pennsylvania, 19401

  • HSHS Sacred Heart Hospital

    Eau Claire, Wisconsin, 54701

  • Crossroads Cancer Center

    Effingham, Illinois, 62401

  • Advocate Sherman Hospital

    Elgin, Illinois, 60123

  • UC San Diego Health System - Encinitas

    Encinitas, California, 92024

  • Ephrata Cancer Center

    Ephrata, Pennsylvania, 17522

  • UPMC Hillman Cancer Center Erie

    Erie, Pennsylvania, 16505

  • Illinois CancerCare-Eureka

    Eureka, Illinois, 61530

  • NorthShore University HealthSystem-Evanston Hospital

    Evanston, Illinois, 60201

  • Inova Schar Cancer Institute

    Fairfax, Virginia, 22031

  • Inova Fair Oaks Hospital

    Fairfax, Virginia, 22033

  • Sanford Broadway Medical Center

    Fargo, North Dakota, 58122

  • Sanford Roger Maris Cancer Center

    Fargo, North Dakota, 58122

  • Parkland Health Center - Farmington

    Farmington, Missouri, 63640

  • Farmington Health Center

    Farmington, Utah, 84025

  • Weisberg Cancer Treatment Center

    Farmington Hills, Michigan, 48334

  • UPMC Cancer Center at UPMC Horizon

    Farrell, Pennsylvania, 16121

  • McLaren Cancer Institute-Flint

    Flint, Michigan, 48532

  • Singh and Arora Hematology Oncology PC

    Flint, Michigan, 48532

  • Poudre Valley Hospital

    Fort Collins, Colorado, 80524

  • Cancer Care and Hematology-Fort Collins

    Fort Collins, Colorado, 80528

  • Ascension Southeast Wisconsin Hospital - Franklin

    Franklin, Wisconsin, 53132

  • Reiman Cancer Center-Ascension Wisconsin Health Center-Rawson

    Franklin, Wisconsin, 53132

  • Kaiser Permanente-Fremont

    Fremont, California, 94538

  • Fresno Cancer Center

    Fresno, California, 93720

  • Kaiser Permanente-Fresno

    Fresno, California, 93720

  • Saint Luke's Cancer Institute - Fruitland

    Fruitland, Idaho, 83619

  • Fox Chase Cancer Center Buckingham

    Furlong, Pennsylvania, 18925

  • Gibbs Cancer Center-Gaffney

    Gaffney, South Carolina, 29341

  • Illinois CancerCare-Galesburg

    Galesburg, Illinois, 61401

  • Western Illinois Cancer Treatment Center

    Galesburg, Illinois, 61401

  • CaroMont Regional Medical Center

    Gastonia, North Carolina, 28054

  • Northwestern Medicine Cancer Center Delnor

    Geneva, Illinois, 60134

  • Tidelands Georgetown Memorial Hospital

    Georgetown, South Carolina, 29440

  • The West Clinic - Wolf River

    Germantown, Tennessee, 38138

  • Aurora Health Care Germantown Health Center

    Germantown, Wisconsin, 53022

  • Adams Cancer Center

    Gettysburg, Pennsylvania, 17325

  • Banner MD Anderson Cancer Center

    Gilbert, Arizona, 85234

  • NorthShore University HealthSystem-Glenbrook Hospital

    Glenview, Illinois, 60026

  • Aurora Cancer Care-Grafton

    Grafton, Wisconsin, 53024

  • Corewell Health Grand Rapids Hospitals - Butterworth Hospital

    Grand Rapids, Michigan, 49503

  • Corewell Health Grand Rapids Hospitals - Helen DeVos Children's Hospital

    Grand Rapids, Michigan, 49503

  • Trinity Health Grand Rapids Hospital

    Grand Rapids, Michigan, 49503

  • Benefis Sletten Cancer Institute

    Great Falls, Montana, 59405

  • UCHealth Greeley Hospital

    Greeley, Colorado, 80631

  • 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

  • UPMC Cancer Centers - Arnold Palmer Pavilion

    Greensburg, Pennsylvania, 15601

  • East Carolina University

    Greenville, North Carolina, 27834

  • Saint Francis Hospital

    Greenville, South Carolina, 29601

  • Prisma Health Cancer Institute - Faris

    Greenville, South Carolina, 29605

  • Saint Francis Cancer Center

    Greenville, South Carolina, 29607

  • Prisma Health Cancer Institute - Eastside

    Greenville, South Carolina, 29615

  • Prisma Health Cancer Institute - Greer

    Greer, South Carolina, 29650

  • Gibbs Cancer Center-Pelham

    Greer, South Carolina, 29651

  • UPMC Pinnacle Cancer Center/Community Osteopathic Campus

    Harrisburg, Pennsylvania, 17109

  • Hartford Hospital

    Hartford, Connecticut, 06102

  • Essentia Health-Hayward Clinic

    Hayward, Wisconsin, 54843

  • Penn State Milton S Hershey Medical Center

    Hershey, Pennsylvania, 17033-0850

  • Essentia Health Hibbing Clinic

    Hibbing, Minnesota, 55746

  • NorthShore University HealthSystem-Highland Park Hospital

    Highland Park, Illinois, 60035

  • Hawaii Cancer Care Inc - Waterfront Plaza

    Honolulu, Hawaii, 96813

  • Queen's Cancer Cenrer - POB I

    Honolulu, Hawaii, 96813

  • Queen's Medical Center

    Honolulu, Hawaii, 96813

  • Straub Clinic and Hospital

    Honolulu, Hawaii, 96813

  • University of Hawaii Cancer Center

    Honolulu, Hawaii, 96813

  • Hawaii Cancer Care Inc-Liliha

    Honolulu, Hawaii, 96817

  • Kuakini Medical Center

    Honolulu, Hawaii, 96817

  • Queen's Cancer Center - Kuakini

    Honolulu, Hawaii, 96817

  • The Cancer Center of Hawaii-Liliha

    Honolulu, Hawaii, 96817

  • Kaiser Permanente Moanalua Medical Center

    Honolulu, Hawaii, 96819

  • Kapiolani Medical Center for Women and Children

    Honolulu, Hawaii, 96826

  • Novant Health Cancer Institute - Huntersville

    Huntersville, North Carolina, 28078

  • Novant Health Presbyterian Medical Center Huntersville

    Huntersville, North Carolina, 28078

  • Indiana University/Melvin and Bren Simon Cancer Center

    Indianapolis, Indiana, 46202

  • Sidney and Lois Eskenazi Hospital

    Indianapolis, Indiana, 46202

  • City of Hope at Irvine Lennar

    Irvine, California, 92618

  • University of Wisconsin Carbone Cancer Center - Johnson Creek

    Johnson Creek, Wisconsin, 53038

  • UPMC-Johnstown/John P. Murtha Regional Cancer Center

    Johnstown, Pennsylvania, 15901

  • Freeman Health System

    Joplin, Missouri, 64804

  • Jupiter Medical Center

    Jupiter, Florida, 33458

  • University of Kansas Cancer Center

    Kansas City, Kansas, 66160

  • University of Kansas Cancer Center - North

    Kansas City, Missouri, 64154

  • CHI Health Good Samaritan

    Kearney, Nebraska, 68847

  • Aurora Cancer Care-Kenosha South

    Kenosha, Wisconsin, 53142

  • Novant Health Cancer Institute - Kernersville

    Kernersville, North Carolina, 27284

  • Illinois CancerCare-Kewanee Clinic

    Kewanee, Illinois, 61443

  • University of Tennessee - Knoxville

    Knoxville, Tennessee, 37920

  • Gundersen Lutheran Medical Center

    La Crosse, Wisconsin, 54601

  • UC San Diego Moores Cancer Center

    La Jolla, California, 92093

  • City of Hope Antelope Valley

    Lancaster, California, 93534

  • 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

  • Lawrence Memorial Hospital

    Lawrence, Kansas, 66044

  • Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center

    Lebanon, New Hampshire, 03756

  • University of Kansas Cancer Center - Lee's Summit

    Lee's Summit, Missouri, 64064

  • Geisinger Medical Oncology-Lewisburg

    Lewisburg, Pennsylvania, 17837

  • Lewistown Hospital

    Lewistown, Pennsylvania, 17044

  • University of Kentucky/Markey Cancer Center

    Lexington, Kentucky, 40536

  • Wilcox Memorial Hospital and Kauai Medical Clinic

    Lihue, Hawaii, 96766

  • AdventHealth Littleton

    Littleton, Colorado, 80122

  • Trinity Health Saint Mary Mercy Livonia Hospital

    Livonia, Michigan, 48154

  • Logan Regional Hospital

    Logan, Utah, 84321

  • Los Angeles General Medical Center

    Los Angeles, California, 90033

  • USC / Norris Comprehensive Cancer Center

    Los Angeles, California, 90033

  • Cedars-Sinai Medical Center

    Los Angeles, California, 90048

  • Jewish Hospital

    Louisville, Kentucky, 40202

  • 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

  • Medical Center of the Rockies

    Loveland, Colorado, 80538

  • Illinois CancerCare-Macomb

    Macomb, Illinois, 61455

  • 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

  • Saint Mary's Oncology/Hematology Associates of Marlette

    Marlette, Michigan, 48453

  • Fremont - Rideout Cancer Center

    Marysville, California, 95901

  • Novant Health Cancer Institute - Matthews

    Matthews, North Carolina, 28105

  • Hillcrest Hospital Cancer Center

    Mayfield Heights, Ohio, 44124

  • Loyola University Medical Center

    Maywood, Illinois, 60153

  • UPMC Cancer Center at UPMC McKeesport

    McKeesport, Pennsylvania, 15132

  • UPMC Hillman Cancer Center at Rocco And Nancy Ortenzio Cancer Pavilion

    Mechanicsburg, Pennsylvania, 17050

  • Summa Health Medina Medical Center

    Medina, Ohio, 44256

  • Froedtert Menomonee Falls Hospital

    Menomonee Falls, Wisconsin, 53051

  • UH Seidman Cancer Center at Lake Health Mentor Campus

    Mentor, Ohio, 44060

  • Ascension Columbia Saint Mary's Hospital-Ozaukee Campus-Mequon

    Mequon, Wisconsin, 53097

  • Saint Luke's Cancer Institute - Meridian

    Meridian, Idaho, 83642

  • East Jefferson General Hospital

    Metairie, Louisiana, 70006

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

    Miami, Florida, 33136

  • Miami Cancer Institute

    Miami, Florida, 33176

  • UM Sylvester Comprehensive Cancer Center at Kendall

    Miami, Florida, 33176

  • UH Seidman Cancer Center at Southwest General Hospital

    Middleburg Heights, Ohio, 44130

  • Aurora Cancer Care-Milwaukee

    Milwaukee, Wisconsin, 53209

  • Ascension Southeast Wisconsin Hospital-Saint Joseph-Milwaukee

    Milwaukee, Wisconsin, 53210

  • Ascension Columbia Saint Mary's Hospital-Milwaukee Campus

    Milwaukee, Wisconsin, 53211

  • Ascension Saint Francis Hospital-Milwaukee

    Milwaukee, Wisconsin, 53215

  • Aurora Saint Luke's Medical Center

    Milwaukee, Wisconsin, 53215

  • Medical College of Wisconsin

    Milwaukee, Wisconsin, 53226

  • Aurora Sinai Medical Center

    Milwaukee, Wisconsin, 53233

  • Kaiser Permanente-Modesto

    Modesto, California, 95356

  • Atrium Health Union/LCI-Union

    Monroe, North Carolina, 28112

  • Forbes Hospital

    Monroeville, Pennsylvania, 15146

  • UPMC Cancer Center - Monroeville

    Monroeville, Pennsylvania, 15146

  • UPMC Hillman Cancer Center in Coraopolis

    Moon Township, Pennsylvania, 15108

  • Novant Health Cancer Institute - Mooresville

    Mooresville, North Carolina, 28117

  • Novant Health Cancer Institute - Mount Airy

    Mount Airy, North Carolina, 27030

  • McLaren Cancer Institute-Macomb

    Mount Clemens, Michigan, 48043

  • Palo Alto Medical Foundation-Camino Division

    Mountain View, California, 94040

  • Intermountain Medical Center

    Murray, Utah, 84107

  • Saint Alphonsus Cancer Care Center-Nampa

    Nampa, Idaho, 83687

  • Saint Luke's Cancer Institute - Nampa

    Nampa, Idaho, 83687

  • Vanderbilt University/Ingram Cancer Center

    Nashville, Tennessee, 37232

  • Rutgers Cancer Institute of New Jersey

    New Brunswick, New Jersey, 08903

  • Delaware Clinical and Laboratory Physicians PA

    Newark, Delaware, 19713

  • Helen F Graham Cancer Center

    Newark, Delaware, 19713

  • Medical Oncology Hematology Consultants PA

    Newark, Delaware, 19713

  • Christiana Care Health System-Christiana Hospital

    Newark, Delaware, 19718

  • Providence Newberg Medical Center

    Newberg, Oregon, 97132

  • Corewell Health Lakeland Hospitals - Niles Hospital

    Niles, Michigan, 49120

  • University of Kansas Cancer Center at North Kansas City Hospital

    North Kansas City, Missouri, 64116

  • Novant Health Cancer Institute - Wilkesboro

    North Wilkesboro, North Carolina, 28659

  • Henry Ford Medical Center-Columbus

    Novi, Michigan, 48377

  • Cancer Care Center of O'Fallon

    O'Fallon, Illinois, 62269

  • Kaiser Permanente Oakland-Broadway

    Oakland, California, 94611

  • Kaiser Permanente-Oakland

    Oakland, California, 94611

  • McKay-Dee Hospital Center

    Ogden, Utah, 84403

  • University of Oklahoma Health Sciences Center

    Oklahoma City, Oklahoma, 73104

  • The University of Kansas Cancer Center - Olathe

    Olathe, Kansas, 66061

  • University of Nebraska Medical Center

    Omaha, Nebraska, 68198

Other trials in United States

Canada1 site

  • University Health Network-Princess Margaret Hospital

    Toronto, Ontario, M5G 2M9

Other trials in Canada

About this study

Official title: A Randomized Phase II/III Trial of De-Intensified Radiation Therapy for Patients With Early-Stage, P16-Positive, Non-Smoking Associated Oropharyngeal Cancer

This phase II/III trial studies how well a reduced dose of radiation therapy works with nivolumab compared to cisplatin in treating patients with human papillomavirus (HPV)-positive oropharyngeal cancer that is early in its growth and may not have spread to other parts of the body (early-stage), and is not associated with smoking. Radiation therapy uses high-energy x-rays to kill tumor cells and shrink tumors. Chemotherapy drugs, such as cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. This trial is being done to see if a reduced dose of radiation therapy and nivolumab works as well as standard dose radiation therapy and cisplatin in treating patients with oropharyngeal cancer.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To demonstrate non-inferiority in terms of progression-free survival (PFS) of concurrent reduced-dose radiation therapy (RT) with cisplatin or concurrent reduced-dose radiation therapy with nivolumab to the current standard of care (standard-dose RT with cisplatin). (Phase II) (Arm 2 [concurrent reduced-dose RT with cisplatin] was dropped after interim futility analysis in phase II.) II. To demonstrate non-inferiority in terms of progression-free survival (PFS) of concurrent reduced-dose radiation therapy (RT) with nivolumab to the current standard of care (standard-dose RT with cisplatin). (Phase II) III. To demonstrate co-primary endpoints of non-inferiority of PFS and superiority of quality of life (QOL) as measured by the MD Anderson Dysphagia Inventory (MDADI) of concurrent reduced-dose radiation with cisplatin or concurrent reduced-dose radiation with nivolumab to the current standard of care (standard-dose RT with cisplatin). (Phase III) (Arm 2 [concurrent reduced-dose RT with cisplatin] was dropped after interim futility analysis in phase II.) IV. To demonstrate co-primary endpoints of non-inferiority of PFS and superiority of quality of life (QOL) as measured by the MD Anderson Dysphagia Inventory [MDADI] of concurrent reduced-dose radiation with nivolumab to the current standard of care (standard-dose RT with cisplatin). (Phase III)

SECONDARY OBJECTIVES:

  1. To compare patterns of failure (local and regional relapse versus distant) and overall survival between the experimental arm and the control arm.

II. To assess long term PFS, overall survival, and toxicity between the experimental arm and the control arm.

III. To determine acute and late toxicity profiles as measured by the Common Terminology Criteria for Adverse Events (CTCAE).

IV. To explore the symptomatic adverse events (AEs) for tolerability of each treatment arm as measured by the Patient-Reported Outcomes (PRO)-CTCAE.

  1. To compare changes in patient-reported outcomes (Hearing Handicap Inventory for Adults-Screening [HHIA-S], European Organization for Research and Treatment of Cancer [EORTC]-Quality of Life Questionnaire [QLQ]30) between the experimental arm and the control arm.

VI. To assess the association of fludeoxyglucose F-18 (FDG)-positron emission tomography (PET)/computed tomography (CT) at baseline with locoregional control and PFS.

VII. To estimate the negative predictive value of the 12-14 weeks post-radiation therapy (RT) FDG-PET/CT in terms of locoregional control rates and PFS rates at 1 and 2 years.

EXPLORATORY OBJECTIVES:

  1. To collect blood and tissue specimens for future translation research. II. To optimize radiotherapy treatment plan quality assurance methodology for radiotherapy planning and imaging.

III. To compare changes in patient-reported outcomes (European Quality of Life Five Dimension Five Level Scale [EQ-5D-5L]) between the experimental arm and the control arm.

IV. To collect Modified Barium Swallow (MBS) data for future review and analysis.

OUTLINE:

PHASE II: Patients are randomized to 1 of 3 arms.

ARM I: Patients undergo standard dose RT as 70 Gy intensity modulated radiation therapy (IMRT) or image-guided radiation therapy (IGRT) over 6 fractions per week and receive 100 mg/m^2/day cisplatin intravenously (IV) over 30-60 minutes on days 1 and 22. Treatment continues for 6 weeks in the absence of disease progression or unacceptable toxicity. Patients receive fludeoxyglucose F-18 (FDG) and undergo positron emission tomography (PET)/computed tomography (CT) or CT during screening and during follow up, and undergo magnetic resonance imaging (MRI) during follow up. Patients may also undergo tissue biopsy and blood sample collection throughout the study.

ARM II (CLOSED TO ACCRUAL 03-FEB-2023): Patients undergo reduced dose RT as 60 Gy IMRT or IGRT once daily (QD) over 5 fractions per week and receive 100 mg/m^2/day cisplatin IV over 30-60 minutes on days 1 and 22. Treatment continues for 6 weeks in the absence of disease progression or unacceptable toxicity. Patients receive FDG and undergo PET/CT or CT during screening and during follow up, and undergo MRI during follow up. Patients may also undergo tissue biopsy and blood sample collection throughout the study.

ARM III: Beginning 1 week prior to radiation, patients receive 240 mg fixed dose nivolumab IV over 30 minutes on day 1. Treatment repeats every 2 weeks (14 days) for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo reduced dose RT as 60 Gy IMRT or IGRT over 6 fractions per week for 5 weeks in the absence of disease progression or unacceptable toxicity. Patients receive FDG and undergo PET/CT or CT during screening and during follow up, and undergo MRI during follow up. Patients may also undergo tissue biopsy and blood sample collection throughout the study.

PHASE III: Patients are randomized to Arm I and/or Arm III.

After completion of study treatment, patients are followed up at 12-14 weeks, every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.

Being tested
Biopsy Procedure, Biospecimen Collection, Cisplatin, Computed Tomography, Fludeoxyglucose F-18
Medical subject headings
Oropharyngeal Neoplasms, Squamous Cell Carcinoma of Head and Neck, Carcinoma, Squamous Cell

What participants receive

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

  • Biopsy ProcedureProcedure or surgery

    Also called Biopsy, BIOPSY_TYPE, Bx

    Undergo tissue biopsy

  • Biospecimen CollectionProcedure or surgery

    Also called Biological Sample Collection, Biospecimen Collected, Sample Collection, Specimen Collection

    Undergo blood sample collection

  • CisplatinDrug

    Also called Abiplatin, Blastolem, Briplatin, CDDP

    Given IV

  • Computed TomographyProcedure or surgery

    Also called CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography

    Undergo CT

  • Fludeoxyglucose F-18Other

    Also called 18FDG, FDG, Fludeoxyglucose (18F), fludeoxyglucose F 18

    Receive FDG

  • Image Guided Radiation TherapyRadiation

    Also called IGRT, Image Guided Radiotherapy, image-guided radiation therapy, Image-Guided Radiotherapy

    Undergo IGRT

  • Intensity-Modulated Radiation TherapyRadiation

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

    Undergo IMRT

  • Magnetic Resonance ImagingProcedure or surgery

    Also called Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan

    Undergo MRI

  • NivolumabBiological

    Also called ABP 206, BCD-263, BMS 936558, BMS-936558

    Given IV

  • Positron Emission TomographyProcedure or surgery

    Also called Medical Imaging, Positron Emission Tomography, PET, PET Scan, Positron emission tomography (procedure)

    Undergo PET

  • Quality-of-Life AssessmentOther

    Also called Quality of Life Assessment

    Ancillary studies

  • Questionnaire AdministrationOther

    Ancillary studies

Study groups in NCT03952585
Study groupRoleWhat they receive
Arm I (Standard RT + cisplatin)Active comparatorPatients undergo standard dose RT as 70 Gy IMRT or IGRT over 6 fractions per week and receive 100 mg/m^2/day cisplatin IV over 30-60 minutes on days 1 and 22. Treatment continues for 6 weeks in the absence of disease progression or unacceptable toxicity. Patients receive FDG and undergo PET/CT or CT during screening and during follow up, and undergo MRI during follow up. Patients may also undergo tissue biopsy and blood sample collection throughout the study.
Receives: Procedure: Biopsy Procedure; Procedure: Biospecimen Collection; Drug: Cisplatin; Procedure: Computed Tomography; Other: Fludeoxyglucose F-18; Radiation: Image Guided Radiation Therapy; Radiation: Intensity-Modulated Radiation Therapy; Procedure: Magnetic Resonance Imaging; Procedure: Positron Emission Tomography; Other: Quality-of-Life Assessment; Other: Questionnaire Administration
Arm II (Reduced RT + cisplatin)ExperimentalPatients undergo reduced dose RT as 60 Gy IMRT or IGRT QD over 5 fractions per week and receive 100 mg/m^2/day cisplatin IV over 30-60 minutes on days 1 and 22. Treatment continues for 6 weeks in the absence of disease progression or unacceptable toxicity. Patients receive FDG and undergo PET/CT or CT during screening and during follow up, and undergo MRI during follow up. Patients may also undergo tissue biopsy and blood sample collection throughout the study.
Receives: Procedure: Biopsy Procedure; Procedure: Biospecimen Collection; Drug: Cisplatin; Procedure: Computed Tomography; Other: Fludeoxyglucose F-18; Radiation: Image Guided Radiation Therapy; Radiation: Intensity-Modulated Radiation Therapy; Procedure: Magnetic Resonance Imaging; Procedure: Positron Emission Tomography; Other: Quality-of-Life Assessment; Other: Questionnaire Administration
Arm III (Reduced RT + nivolumab)ExperimentalBeginning 1 week prior to radiation, patients receive 240 mg fixed dose nivolumab IV over 30 minutes on day 1. Treatment repeats every 2 weeks (14 days) for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo reduced dose RT as 60 Gy IMRT or IGRT over 6 fractions per week for 5 weeks in the absence of disease progression or unacceptable toxicity. Patients receive FDG and undergo PET/CT or CT during screening and during follow up, and undergo MRI during follow up. Patients may also undergo tissue biopsy and blood sample collection throughout the study.
Receives: Procedure: Biopsy Procedure; Procedure: Biospecimen Collection; Procedure: Computed Tomography; Other: Fludeoxyglucose F-18; Radiation: Image Guided Radiation Therapy; Radiation: Intensity-Modulated Radiation Therapy; Biological: Nivolumab; Procedure: Positron Emission Tomography; 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. Progression-free Survival (PFS) (Phase II) (Percentage of Participants Alive Without Progression)

    Progression is defined as local-regional progression or recurrence, distant metastasis, death due to any reason, salvage surgery of primary with tumor present/unknown, salvage neck dissection with tumor present/unknown, > 20 weeks from end of radiation therapy. Progression-free survival rates are estimated using the Kaplan-Meier method, censoring participants alive at time of analysis.

    The primary phase IIR endpoint is tested using a confidence interval (CI) approach with each experimental arm compared to the standard arm (Arm 1).

    Measured: From randomization to first progression or last follow-up. Maximum follow-up at the time of analysis was 4.6 years. The 1- and 2-year estimates are reported.

  2. Progression-free Survival (Phase III) (Percentage of Participants Alive Without Progression)

    Progression is defined as local-regional progression or recurrence, distant metastasis, death due to any reason, salvage surgery of primary with tumor present/unknown, salvage neck dissection with tumor present/unknown, > 20 weeks from end of radiation therapy. Progression-free survival rates are estimated using the Kaplan-Meier method, censoring participants alive at time of analysis.

    Measured: From randomization to first progression or last follow-up. Maximum follow-up was 4.6 years.

  3. MD Anderson Dysphagia Inventory (MDADI) Global Quality of Life (QOL) Score

    The M. D. Anderson Dysphagia Inventory (MDADI) assesses how patients view their swallowing ability as a result of treatment and how this affects their QOL. It consists of a global quality of life question and a functional, emotional, and physical subscale. The global QOL question ranges from 1 to 5 and multiplied by 20 to obtain a score with a range of 0 to 100. Higher scores indicate better functioning.

    Measured: Baseline to two years

Secondary outcomes (10)

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

    Locoregional failure is defined as local-regional progression or recurrence, death due to study cancer or unknown causes, salvage neck dissection with tumor present/unknown. Locoregional failure rates are estimated the cumulative incidence method, treating distant metastasis and death due to any reason other than study cancer or unknown as competing risks, and otherwise censoring participants alive at time of analysis. Each experimental arm is compared to the standard arm (Arm I).

    Measured: From randomization to first failure, competing event, or last known follow-up, whichever occurs first. Maximum follow-up at the time of analysis was 4.6 years. The 1- and 2-year estimates are reported.

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

    Distant failure is defined as the occurrence of distant metastasis. Distant failure rates are estimated the cumulative incidence method, treating local-regional progression or recurrence, death due to any reason, salvage neck dissection with tumor present/unknown as competing risks, and otherwise censoring participants alive at time of analysis. Each experimental arm is compared to the standard arm (Arm I).

    Measured: From randomization to first failure, competing event, or last known follow-up, whichever occurs first. Maximum follow-up at the time of analysis was 4.6 years. The 1- and 2-year estimates are reported.

  3. Overall Survival (Percentage of Participants Alive)

    Survival rates are estimated using the Kaplan-Meier method, censoring participants alive at time of analysis.

    Measured: From randomization to death from any cause or last follow-up. Maximum follow-up at the time of analysis was 4.6 years. The 1- and 2-year estimates are reported.

  4. Number of Participants by Highest Grade Adverse Event Reported

    Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 grades adverse event severity as follows: 1 = mild, 2 = moderate, 3 = severe, 4 = life-threatening, 5 = death related to adverse event. Summary data is provided in this outcome measure; see Adverse Events Module for specific adverse event data.

    Measured: From randomization to last known follow-up. Maximum follow-up at the time of analysis was 4.6 years.

  5. Hearing

    Measured as Hearing Handicap Inventory for Adults-Screening (HHIA-S).

    Measured: Baseline up to 24 months from end of radiation therapy (RT)

  6. Quality of Life

    Measured by the European Organization for Research and Treatment of Cancer (EORTC)-Quality of Life Questionnaire (QLQ)30.

    Measured: Baseline up to 24 months from end of RT

  7. Fludeoxyglucose F-18 (FDG)-Positron Emission Tomography (PET)/Computed Tomography (CT) Locoregional Control

    Will be associated with PFS.

    Measured: Up to 6 years

  8. Negative Predictive Value of Post-RT FDG-PET/CT for Locoregional Control

    The negative predictive value of FDG-PET/CT for locoregional control will be estimated using binomial proportions and confidence intervals based on normal approximation.

    Measured: At 1 and 2 years

  9. Negative Predictive Value of Post-RT FDG-PET/CT for PFS

    The negative predictive value of FDG-PET/CT PFS will be estimated using binomial proportions and confidence intervals based on normal approximation.

    Measured: At 1 and 2 years

  10. Incidence of Adverse Events

    Measured using Patient-Reported Outcomes (PRO)-CTCAE. For each symptom, counts and frequencies will be provided for the worst score experienced by the patient by treatment arm. The proportion of patients with scores >= 1 and >= 3 will be compared between groups using a Chi-square test, or Fisher's exact test if cell frequencies are < 5, using a significance level of 0.05. Analysis of changes in patient reported outcomes over time will analyzed by fitting generalized estimating equations (GEE) models using a logit link (dichotomizing the symptom scores as 0 vs. > 1 and 0-2 vs. 3-4) with time of assessment, treatment arm, and treatment-by-time interaction terms in the model.

    Measured: Up to 6 years

Timeline

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

  1. First posted16 May 2019
  2. Study start9 Oct 2019
  3. Primary completion1 Mar 2024
  4. Study completion11 Dec 2026 (estimated)

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
384 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03952585
Sponsor's protocol ID
NCI-2019-03015
Other IDs
NCI-2019-03015, NRG-HN005, NRG-HN005, U10CA180868
Status last verified
Jun 2026
First submitted
15 May 2019
Last updated
2 Jul 2026
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page

Questions about this trial

What is this clinical trial studying?

A Phase 2/3 study testing Biopsy Procedure, Biospecimen Collection and Cisplatin in people with Basaloid Squamous Cell Carcinoma and Clinical Stage I HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8, run by National Cancer Institute (NCI) at 494 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 36 inclusion and 26 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: under way, not looking for participants, as of the sponsor's last update on 2 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 494 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 2 May 2025). 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?

Progression-free Survival (PFS) (Phase II) (Percentage of Participants Alive Without Progression) (time frame: From randomization to first progression or last follow-up. Maximum follow-up at the time of analysis was 4.6 years. The 1- and 2-year estimates are reported.). 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 NCT03952585.

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 2 Jul 2026.

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