Recruiting
Phase 3

Cetuximab vs. Chemotherapy

Sponsor:

NRG Oncology

Code:

NCT07441681

Conditions

Clinical Stage I HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8

Clinical Stage II HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8

Clinical Stage III HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8

Head and Neck Squamous Cell Carcinoma

Stage III Hypopharyngeal Carcinoma AJCC v8

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Biospecimen Collection

Carboplatin

Cetuximab

Computed Tomography

Intensity-Modulated Radiation Therapy

Study Details

Brief summary:

This phase III trial compares cetuxumab to chemotherapy, carboplatin and paclitaxel, with intensity modulated radiation therapy for the treatment of patients with head and neck cancer who are unable to receive cisplatin. Cetuximab is in a class of medications called monoclonal antibodies. It binds to a protein called EGFR, which is found on some types of cancer cells. This may help keep cancer cells from growing. Carboplatin is in a class of medications known as platinum-containing compounds. It works in a way similar to the anticancer drug cisplatin, but may be better tolerated than cisplatin. Carboplatin works by killing, stopping or slowing the growth of cancer cells. Paclitaxel is in a class of medications called antimicrotubule agents. It stops cancer cells from growing and dividing and may kill them. Intensity modulated radiation therapy is a type of 3-dimensional radiation therapy that uses computer-generated images to show the size and shape of the tumor. Thin beams of radiation of different intensities are aimed at the tumor from many angles. This type of radiation therapy reduces the damage to healthy tissue near the tumor. It is not yet know if cetxiumab or chemotherapy, with intensity modulated radiation therapy works best for the treatment of patients with head and neck cancer who are unable to receive cisplatin.

Conditions

Clinical Stage I HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8

Clinical Stage II HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8

Clinical Stage III HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8

Head and Neck Squamous Cell Carcinoma

Stage III Hypopharyngeal Carcinoma AJCC v8

Study ID

NCT07441681

Start date

Jul 31, 2026

Status verified date

Aug, 2026

Completion date

Nov 30, 2040

Anticipated

Primary completion date

Nov 30, 2035

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Inclusion Criteria:

  • Patients must have pathologically confirmed, previously untreated, unresected squamous cell carcinoma of the larynx, hypopharynx, oropharynx, or oral cavity
  • Local evaluation of p16 status is required for all oropharynx patients prior to registration
  • Local evaluation of p16 status is recommended for non-oropharynx patients prior to registration
  • Locoregionally advanced head and neck squamous cell carcinoma (HNSCC) defined as:

  • Non-oropharynx and p16-negative oropharynx cancer: American Joint Commission on Cancer (AJCC) 8th edition stage III-IVB

  • Laryngeal, Hypopharyngeal, Oral Cavity, and p16-Negative Oropharyngeal Primaries:

  • AJCC 8th Edition TNM: T3-4b N0 M0 AJCC 8th Edition Stage: III-IVB
  • AJCC 8th Edition TNM: T1-4b N1-3 M0 AJCC 8th Edition Stage: III-IVB
  • p16-positive oropharynx cancer: AJCC 8th edition stage III and selected stage I-II based on smoking status in pack-years

  • Eligible p16-Positive Oropharyngeal Primaries

  • AJCC 8th Edition TNM: T1-2 N1 M0 AJCC 8th Edition Stage: I Pack-Years: > 10
  • AJCC 8th Edition TNM: T1-2 N2 M0 AJCC 8th Edition Stage: II Pack-Years: any
  • AJCC 8th Edition TNM: T3 N0-1 M0 AJCC 8th Edition Stage: II Pack-Years: > 10
  • AJCC 8th Edition TNM: T3 N2 M0 AJCC 8th Edition Stage: II Pack-Years: any
  • AJCC 8th Edition TNM: T1-3 N3 M0 AJCC 8th Edition Stage: III Pack-Years: any
  • AJCC 8th Edition TNM: T4 N0-3 M0 AJCC 8th Edition Stage: III Pack-Years: any

  • Note: Number of pack-years = \[Frequency of smoking (number of cigarettes per day) × duration of cigarette smoking (years)\] / 20
  • Note: Cigar and pipe tobacco consumption is not included in calculating the lifetime pack-years. Marijuana consumption is likewise not considered in this calculation. There is also no clear scientific evidence regarding the role of chewing tobacco-containing products in oropharyngeal cancer, although this is possibly more concerning given the proximity of the oral cavity and oropharynx. In any case, investigators should not count use of non-cigarette tobacco products in the pack-years calculation
  • The following are required prior to registration:

  • Imaging of the head and neck with a neck CT or MRI (with contrast, unless contraindicated) or PET/CT which includes diagnostic-quality CT of the neck (with contrast, unless contraindicated)
  • Chest imaging: Chest CT (with contrast, unless contraindicated) or PET/CT
  • Age ≥ 18
  • Complete the online tool at www.nrgoncology.org prior to registration and record the (modified) Charleston Comorbidity Index (CCI), Head and Neck Cancer Intergroup (HNCIG) omega, and G-8 scores on the registration form in Oncology Patient Enrollment Network (OPEN)
  • Patients must have a contraindication to cisplatin as defined in the following bullet points:

  • Absolute or relative contraindication to cisplatin, defined as ONE OR MORE of the following prior to registration:

  • Creatinine clearance (CrCl) < 60 mL/min by the Cockroft-Gault formula
  • Pre-existing peripheral (sensory or motor) neuropathy grade ≥ 2 (per Common Terminology Criteria for Adverse Events \[CTCAE\] version \[v\] 5.0)
  • 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 OR
  • age ≥ 70 with Head and Neck Cancer Intergroup (HNCIG) omega score < 0.80 prior to registration OR
  • Age < 70 with ALL of the following conditions prior to registration (see Appendix II for calculation instructions):

  • HNCIG omega score < 0.80
  • (Modified) Charlson Comorbidity Index (CCI) ≥ 1
  • G-8 score ≤ 14
  • Not pregnant and not nursing
  • Participants must be able to safely receive the radiation and drug regimens per current Food and Drug Administration (FDA)-approved package insert(s), treating investigator's discretion, and institutional guidelines
  • No prior systemic therapy for the study cancer; note that prior systemic therapy for a different cancer is allowable
  • No prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields
  • No prior surgery for the study cancer

Study Design

Enrollment

454 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Arm 1 (IMRT, cetuximab)

Patients undergo IMRT 5 days per week for 35 treatments. Starting within 7 days prior to radiation, patients receive a loading dose of cetuximab IV and then concurrently with radiation on day 1 of each cycle. Cycles repeat every 7 days for 7 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo CT scan, PET scan on study and blood sample collection throughout the study. Patients may undergo PET scan or MRI during screening.

active comparator: Arm 2 (IMRT, carboplatin, paclitaxel)

Patients undergo IMRT 5 days per week for 35 treatments. Starting on day 1 of radiation, patients receive concurrent carboplatin IV and paclitaxel on day 1 of each cycle. Cycles repeat every 7 days for 7 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo CT scan, PET scan on study and blood sample collection throughout the study. Patients may undergo PET scan or MRI during screening.

Interventions

Biospecimen Collection

Undergo blood sample collection

Carboplatin

Given IV

Cetuximab

Given IV

Computed Tomography

Undergo CT scan

Intensity-Modulated Radiation Therapy

Undergo IMRT

Magnetic Resonance Imaging

Undergo MRI

Paclitaxel

Given IV

Positron Emission Tomography

Undergo PET scan

Survey Administration

Ancillary studies

Primary outcome measure

  • Progression free survival (PFS) [ Time Frame: From randomization until locoregional failure, distant failure, or death due to any cause, up to 8 years ]

Central Contacts and Locations

Locations

Tower Cancer Research Foundation

Recruiting

Beverly Hills, California, United States, 90211

Contacts

Site Public Contact

towercancerresearch@toweroncology.com

Principal Investigator:

Zachary S. Zumsteg

USC / Norris Comprehensive Cancer Center

Recruiting

Los Angeles, California, United States, 90033

Contacts

Site Public Contact

323-865-0451

Principal Investigator:

Jacob S. Thomas

Cedars-Sinai Medical Center

Recruiting

Los Angeles, California, United States, 90048

Contacts

Site Public Contact

310-423-2133Cancer.trial.info@cshs.org

Principal Investigator:

Zachary S. Zumsteg

Helen F Graham Cancer Center

Recruiting

Newark, Delaware, United States, 19713

Contacts

Site Public Contact

302-623-4450lbarone@christianacare.org

Principal Investigator:

Gregory A. Masters

Medical Oncology Hematology Consultants PA

Recruiting

Newark, Delaware, United States, 19713

Contacts

Site Public Contact

302-623-4450lbarone@christianacare.org

Principal Investigator:

Gregory A. Masters

Christiana Care Health System-Christiana Hospital

Recruiting

Newark, Delaware, United States, 19718

Contacts

Site Public Contact

302-623-4450lbarone@christianacare.org

Principal Investigator:

Gregory A. Masters

Christiana Care Health System-Wilmington Hospital

Recruiting

Wilmington, Delaware, United States, 19801

Contacts

Site Public Contact

302-623-4450lbarone@christianacare.org

Principal Investigator:

Gregory A. Masters

Bay Pines VA Healthcare System

Recruiting

Bay Pines, Florida, United States, 33744

Contacts

Site Public Contact

727-398-6661vhabayresearch@va.gov

Principal Investigator:

Ryan J. Burri

OSF Saint Joseph Medical Center

Recruiting

Bloomington, Illinois, United States, 61701

Contacts

Site Public Contact

309-243-3605andersonj@illinoiscancercare.com

Principal Investigator:

Bryan A. Faller

Illinois CancerCare-Bloomington

Recruiting

Bloomington, Illinois, United States, 61704

Contacts

Site Public Contact

309-243-3605andersonj@illinoiscancercare.com

Principal Investigator:

Bryan A. Faller

Illinois CancerCare-Canton

Recruiting

Canton, Illinois, United States, 61520

Contacts

Site Public Contact

309-243-3605andersonj@illinoiscancercare.com

Principal Investigator:

Bryan A. Faller

Illinois CancerCare-Carthage

Recruiting

Carthage, Illinois, United States, 62321

Contacts

Site Public Contact

309-243-3605andersonj@illinoiscancercare.com

Principal Investigator:

Bryan A. Faller

Northwestern University

Recruiting

Chicago, Illinois, United States, 60611

Contacts

Site Public Contact

312-695-1301cancer@northwestern.edu

Principal Investigator:

Laila A. Gharzai

Cancer Care Specialists of Illinois - Decatur

Recruiting

Decatur, Illinois, United States, 62526

Contacts

Site Public Contact

217-876-4762morganthaler.jodi@mhsil.com

Principal Investigator:

Bryan A. Faller

Decatur Memorial Hospital

Recruiting

Decatur, Illinois, United States, 62526

Contacts

Site Public Contact

217-876-4762morganthaler.jodi@mhsil.com

Principal Investigator:

Bryan A. Faller

Illinois CancerCare-Eureka

Recruiting

Eureka, Illinois, United States, 61530

Contacts

Site Public Contact

309-243-3605andersonj@illinoiscancercare.com

Principal Investigator:

Bryan A. Faller

Illinois CancerCare-Galesburg

Recruiting

Galesburg, Illinois, United States, 61401

Contacts

Site Public Contact

309-243-3605andersonj@illinoiscancercare.com

Principal Investigator:

Bryan A. Faller

Northwestern Medicine Glenview Outpatient Center

Recruiting

Glenview, Illinois, United States, 60026

Contacts

Site Public Contact

312-695-1102

Principal Investigator:

Laila A. Gharzai

Northwestern Medicine Grayslake Outpatient Center

Recruiting

Grayslake, Illinois, United States, 60030

Contacts

Site Public Contact

312-695-1102

Principal Investigator:

Laila A. Gharzai

Illinois CancerCare-Kewanee Clinic

Recruiting

Kewanee, Illinois, United States, 61443

Contacts

Site Public Contact

309-243-3605andersonj@illinoiscancercare.com

Principal Investigator:

Bryan A. Faller

Northwestern Medicine Lake Forest Hospital

Recruiting

Lake Forest, Illinois, United States, 60045

Contacts

Site Public Contact

cancertrials@northwestern.edu

Principal Investigator:

Laila A. Gharzai

Illinois CancerCare-Macomb

Recruiting

Macomb, Illinois, United States, 61455

Contacts

Site Public Contact

309-243-3605andersonj@illinoiscancercare.com

Principal Investigator:

Bryan A. Faller

Cancer Care Center of O'Fallon

Recruiting

O'Fallon, Illinois, United States, 62269

Contacts

Site Public Contact

217-876-4762morganthaler.jodi@mhsil.com

Principal Investigator:

Bryan A. Faller

HSHS Saint Elizabeth's Hospital

Recruiting

O'Fallon, Illinois, United States, 62269

Contacts

Site Public Contact

217-876-4762morganthaler.jodi@mhsil.com

Principal Investigator:

Bryan A. Faller

Northwestern Medicine Orland Park

Recruiting

Orland Park, Illinois, United States, 60462

Contacts

Site Public Contact

nctnprogram_rhlccc@northwestern.edu

Principal Investigator:

Laila A. Gharzai

Illinois CancerCare-Ottawa Clinic

Recruiting

Ottawa, Illinois, United States, 61350

Contacts

Site Public Contact

309-243-3605andersonj@illinoiscancercare.com

Principal Investigator:

Bryan A. Faller

Illinois CancerCare-Pekin

Recruiting

Pekin, Illinois, United States, 61554

Contacts

Site Public Contact

309-243-3605andersonj@illinoiscancercare.com

Principal Investigator:

Bryan A. Faller

Illinois CancerCare-Peoria

Recruiting

Peoria, Illinois, United States, 61615

Contacts

Site Public Contact

309-243-3605andersonj@illinoiscancercare.com

Principal Investigator:

Bryan A. Faller

OSF Saint Francis Radiation Oncology at Peoria Cancer Center

Recruiting

Peoria, Illinois, United States, 61615

Contacts

Site Public Contact

309-243-3605andersonj@illinoiscancercare.com

Principal Investigator:

Bryan A. Faller

OSF Saint Francis Medical Center

Recruiting

Peoria, Illinois, United States, 61637

Contacts

Site Public Contact

309-243-3605andersonj@illinoiscancercare.com

Principal Investigator:

Bryan A. Faller

Illinois CancerCare-Peru

Recruiting

Peru, Illinois, United States, 61354

Contacts

Site Public Contact

309-243-3605andersonj@illinoiscancercare.com

Principal Investigator:

Bryan A. Faller

Illinois CancerCare-Princeton

Recruiting

Princeton, Illinois, United States, 61356

Contacts

Site Public Contact

309-243-3605andersonj@illinoiscancercare.com

Principal Investigator:

Bryan A. Faller

Illinois CancerCare - Washington

Recruiting

Washington, Illinois, United States, 61571

Contacts

Site Public Contact

309-243-3605andersonj@illinoiscancercare.com

Principal Investigator:

Bryan A. Faller

Mercy Hospital

Recruiting

Cedar Rapids, Iowa, United States, 52403

Contacts

Site Public Contact

319-365-4673

Principal Investigator:

Deborah W. Wilbur

Oncology Associates at Mercy Medical Center

Recruiting

Cedar Rapids, Iowa, United States, 52403

Contacts

Site Public Contact

319-363-2690

Principal Investigator:

Deborah W. Wilbur

University of Kansas Cancer Center

Recruiting

Kansas City, Kansas, United States, 66160

Contacts

Site Public Contact

913-588-3671KUCC_Navigation@kumc.edu

Principal Investigator:

Christopher Lominska

University of Kansas Cancer Center-Overland Park

Recruiting

Overland Park, Kansas, United States, 66210

Contacts

Site Public Contact

913-588-3671KUCC_Navigation@kumc.edu

Principal Investigator:

Christopher Lominska

University of Kansas Hospital-Indian Creek Campus

Recruiting

Overland Park, Kansas, United States, 66211

Contacts

Site Public Contact

913-588-3671KUCC_Navigation@kumc.edu

Principal Investigator:

Christopher Lominska

University of Kansas Health System Saint Francis Campus

Recruiting

Topeka, Kansas, United States, 66606

Contacts

Site Public Contact

785-295-8000

Principal Investigator:

Christopher Lominska

University of Kansas Hospital-Westwood Cancer Center

Recruiting

Westwood, Kansas, United States, 66205

Contacts

Site Public Contact

913-588-3671KUCC_Navigation@kumc.edu

Principal Investigator:

Christopher Lominska

University of Kentucky/Markey Cancer Center

Recruiting

Lexington, Kentucky, United States, 40536

Contacts

Site Public Contact

859-257-3379

Principal Investigator:

Susanne M. Arnold

The James Graham Brown Cancer Center at University of Louisville

Recruiting

Louisville, Kentucky, United States, 40202

Contacts

Site Public Contact

502-562-3429

Principal Investigator:

Rebecca A. Redman

UofL Health Medical Center Northeast

Recruiting

Louisville, Kentucky, United States, 40245

Contacts

Site Public Contact

502-852-2755ctoinfo@louisville.edu

Principal Investigator:

Rebecca A. Redman

Saint Francis Medical Center

Recruiting

Cape Girardeau, Missouri, United States, 63703

Contacts

Site Public Contact

573-334-2230sfmc@sfmc.net

Principal Investigator:

Bryan A. Faller

University of Kansas Cancer Center - Briarcliff

Recruiting

Kansas City, Missouri, United States, 64116

Contacts

Site Public Contact

913-588-3671

Principal Investigator:

Christopher Lominska

University of Kansas Cancer Center - North

Recruiting

Kansas City, Missouri, United States, 64154

Contacts

Site Public Contact

913-588-3671KUCC_Navigation@kumc.edu

Principal Investigator:

Christopher Lominska

University of Kansas Cancer Center - Lee's Summit

Recruiting

Lee's Summit, Missouri, United States, 64064

Contacts

Site Public Contact

913-588-3671KUCC_Navigation@kumc.edu

Principal Investigator:

Christopher Lominska

Stony Brook University Medical Center

Recruiting

Stony Brook, New York, United States, 11794

Contacts

Site Public Contact

800-862-2215

Principal Investigator:

Achuta K. Guddati

University of Cincinnati Cancer Center-UC Medical Center

Recruiting

Cincinnati, Ohio, United States, 45219

Contacts

Site Public Contact

513-584-7698cancer@uchealth.com

Principal Investigator:

Kerri McGovern

ProMedica Flower Hospital

Recruiting

Sylvania, Ohio, United States, 43560

Contacts

Site Public Contact

419-824-1842PCIOncResearch@promedica.org

Principal Investigator:

Ahmed G. Elsayed

ProMedica Toledo Hospital/Russell J Ebeid Children's Hospital

Recruiting

Toledo, Ohio, United States, 43606

Contacts

Site Public Contact

419-824-1842PCIOncResearch@promedica.org

Principal Investigator:

Ahmed G. Elsayed

University of Cincinnati Cancer Center-West Chester

Recruiting

West Chester, Ohio, United States, 45069

Contacts

Site Public Contact

513-584-7698cancer@uchealth.com

Principal Investigator:

Kerri McGovern

Christiana Care Health System-Concord Health Center

Recruiting

Chadds Ford, Pennsylvania, United States, 19317

Contacts

Site Public Contact

302-623-4450lbarone@christianacare.org

Principal Investigator:

Gregory A. Masters

Aspirus Cancer Care-Antigo-Volm Cancer Center

Recruiting

Antigo, Wisconsin, United States, 54409

Contacts

Site Public Contact

715-623-9869Juli.Alford@aspirus.org

Principal Investigator:

Andrew J. Huang

Froedtert Menomonee Falls Hospital

Recruiting

Menomonee Falls, Wisconsin, United States, 53051

Contacts

Site Public Contact

262-257-5100

Principal Investigator:

Musaddiq J. Awan

Medical College of Wisconsin

Recruiting

Milwaukee, Wisconsin, United States, 53226

Contacts

Site Public Contact

414-805-3666

Principal Investigator:

Musaddiq J. Awan

Froedtert and MCW Moorland Reserve Health Center

Recruiting

New Berlin, Wisconsin, United States, 53151

Contacts

Site Public Contact

414-805-0505

Principal Investigator:

Musaddiq J. Awan

Drexel Town Square Health Center

Recruiting

Oak Creek, Wisconsin, United States, 53154

Contacts

Site Public Contact

414-805-0505

Principal Investigator:

Musaddiq J. Awan

Aspirus Cancer Care-Rhinelander-James Beck Cancer Center

Recruiting

Rhinelander, Wisconsin, United States, 54501

Contacts

Site Public Contact

715-847-2353Beth.Knetter@aspirus.org

Principal Investigator:

Andrew J. Huang

Aspirus Cancer Care - Stevens Point

Recruiting

Stevens Point, Wisconsin, United States, 54481

Contacts

Site Public Contact

715-847-2353Beth.Knetter@aspirus.org

Principal Investigator:

Andrew J. Huang

Aspirus Cancer Care-Wausau

Recruiting

Wausau, Wisconsin, United States, 54401

Contacts

Site Public Contact

877-405-6866

Principal Investigator:

Andrew J. Huang

Froedtert West Bend Hospital/Kraemer Cancer Center

Recruiting

West Bend, Wisconsin, United States, 53095

Contacts

Site Public Contact

414-805-0505

Principal Investigator:

Musaddiq J. Awan

Aspirus Cancer Care - Wisconsin Rapids

Recruiting

Wisconsin Rapids, Wisconsin, United States, 54494

Contacts

Site Public Contact

715-422-7718

Principal Investigator:

Andrew J. Huang

More Information

Sponsor

NRG Oncology

Last update posted

Aug 17, 2026

Last verified

Aug, 2026

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-03. This information was provided to ClinicalTrials.gov by NRG Oncology on 2026-08-17.