Clinical Stage I HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8Phase 3NCT07441681
Comparing Radiation Plus Cetuximab to Radiation Plus Chemotherapy in People With Head and Neck Cancer Who Cannot Receive Cisplatin
A Phase 3 study testing Biospecimen Collection, Carboplatin and Cetuximab in people with Clinical Stage I HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8 and Clinical Stage II HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8, run by NRG Oncology at 63 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- 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
- What is being tested?
- Biospecimen Collection, Carboplatin and Cetuximab
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 454 participants
- Where
- 63 sitesUnited States
- Study dates
- 31 Jul 2026to 30 Nov 2040
- Phase
- Phase 3
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
- 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:
Show all 40Show fewer
- 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
Who cannot join
None listed.
Trial locations and contacts
63 sites in 1 country. Contact the study team or a site near you to ask about taking part.
63 sites in 1 country
United States63 sites, 63 recruiting
- Recruiting
Aspirus Cancer Care-Antigo-Volm Cancer Center
Antigo, Wisconsin, 54409
Site Public Contact, 715-623-9869, Juli.Alford@aspirus.org
Andrew J. Huang
- Recruiting
Bay Pines VA Healthcare System
Bay Pines, Florida, 33744
Site Public Contact, 727-398-6661, vhabayresearch@va.gov
Ryan J. Burri
- Recruiting
Tower Cancer Research Foundation
Beverly Hills, California, 90211
Site Public Contact, towercancerresearch@toweroncology.com
Zachary S. Zumsteg
- Recruiting
OSF Saint Joseph Medical Center
Bloomington, Illinois, 61701
Site Public Contact, 309-243-3605, andersonj@illinoiscancercare.com
Bryan A. Faller
- Recruiting
Illinois CancerCare-Bloomington
Bloomington, Illinois, 61704
Site Public Contact, 309-243-3605, andersonj@illinoiscancercare.com
Bryan A. Faller
- Recruiting
Illinois CancerCare-Canton
Canton, Illinois, 61520
Site Public Contact, 309-243-3605, andersonj@illinoiscancercare.com
Bryan A. Faller
- Recruiting
Saint Francis Medical Center
Cape Girardeau, Missouri, 63703
Site Public Contact, 573-334-2230, sfmc@sfmc.net
Bryan A. Faller
- Recruiting
Illinois CancerCare-Carthage
Carthage, Illinois, 62321
Site Public Contact, 309-243-3605, andersonj@illinoiscancercare.com
Bryan A. Faller
- Recruiting
Mercy Hospital
Cedar Rapids, Iowa, 52403
Site Public Contact, 319-365-4673
Deborah W. Wilbur
- Recruiting
Oncology Associates at Mercy Medical Center
Cedar Rapids, Iowa, 52403
Site Public Contact, 319-363-2690
Deborah W. Wilbur
- Recruiting
Christiana Care Health System-Concord Health Center
Chadds Ford, Pennsylvania, 19317
Site Public Contact, 302-623-4450, lbarone@christianacare.org
Gregory A. Masters
- Recruiting
Northwestern University
Chicago, Illinois, 60611
Site Public Contact, 312-695-1301, cancer@northwestern.edu
Laila A. Gharzai
- Recruiting
University of Cincinnati Cancer Center-UC Medical Center
Cincinnati, Ohio, 45219
Site Public Contact, 513-584-7698, cancer@uchealth.com
Kerri McGovern
- Recruiting
Cancer Care Specialists of Illinois - Decatur
Decatur, Illinois, 62526
Site Public Contact, 217-876-4762, morganthaler.jodi@mhsil.com
Bryan A. Faller
- Recruiting
Decatur Memorial Hospital
Decatur, Illinois, 62526
Site Public Contact, 217-876-4762, morganthaler.jodi@mhsil.com
Bryan A. Faller
- Recruiting
Illinois CancerCare-Eureka
Eureka, Illinois, 61530
Site Public Contact, 309-243-3605, andersonj@illinoiscancercare.com
Bryan A. Faller
- Recruiting
Illinois CancerCare-Galesburg
Galesburg, Illinois, 61401
Site Public Contact, 309-243-3605, andersonj@illinoiscancercare.com
Bryan A. Faller
- Recruiting
Northwestern Medicine Glenview Outpatient Center
Glenview, Illinois, 60026
Site Public Contact, 312-695-1102
Laila A. Gharzai
- Recruiting
Northwestern Medicine Grayslake Outpatient Center
Grayslake, Illinois, 60030
Site Public Contact, 312-695-1102
Laila A. Gharzai
- Recruiting
University of Kansas Cancer Center
Kansas City, Kansas, 66160
Site Public Contact, 913-588-3671, KUCC_Navigation@kumc.edu
Christopher Lominska
- Recruiting
University of Kansas Cancer Center - Briarcliff
Kansas City, Missouri, 64116
Site Public Contact, 913-588-3671
Christopher Lominska
- Recruiting
University of Kansas Cancer Center - North
Kansas City, Missouri, 64154
Site Public Contact, 913-588-3671, KUCC_Navigation@kumc.edu
Christopher Lominska
- Recruiting
Illinois CancerCare-Kewanee Clinic
Kewanee, Illinois, 61443
Site Public Contact, 309-243-3605, andersonj@illinoiscancercare.com
Bryan A. Faller
- Recruiting
Northwestern Medicine Lake Forest Hospital
Lake Forest, Illinois, 60045
Site Public Contact, cancertrials@northwestern.edu
Laila A. Gharzai
- Recruiting
University of Kansas Cancer Center - Lee's Summit
Lee's Summit, Missouri, 64064
Site Public Contact, 913-588-3671, KUCC_Navigation@kumc.edu
Christopher Lominska
- Recruiting
University of Kentucky/Markey Cancer Center
Lexington, Kentucky, 40536
Site Public Contact, 859-257-3379
Susanne M. Arnold
- Recruiting
USC / Norris Comprehensive Cancer Center
Los Angeles, California, 90033
Site Public Contact, 323-865-0451
Jacob S. Thomas
- Recruiting
Cedars-Sinai Medical Center
Los Angeles, California, 90048
Site Public Contact, 310-423-2133, Cancer.trial.info@cshs.org
Zachary S. Zumsteg
- Recruiting
The James Graham Brown Cancer Center at University of Louisville
Louisville, Kentucky, 40202
Site Public Contact, 502-562-3429
Rebecca A. Redman
- Recruiting
UofL Health Medical Center Northeast
Louisville, Kentucky, 40245
Site Public Contact, 502-852-2755, ctoinfo@louisville.edu
Rebecca A. Redman
- Recruiting
Illinois CancerCare-Macomb
Macomb, Illinois, 61455
Site Public Contact, 309-243-3605, andersonj@illinoiscancercare.com
Bryan A. Faller
- Recruiting
Froedtert Menomonee Falls Hospital
Menomonee Falls, Wisconsin, 53051
Site Public Contact, 262-257-5100
Musaddiq J. Awan
- Recruiting
Medical College of Wisconsin
Milwaukee, Wisconsin, 53226
Site Public Contact, 414-805-3666
Musaddiq J. Awan
- Recruiting
Froedtert and MCW Moorland Reserve Health Center
New Berlin, Wisconsin, 53151
Site Public Contact, 414-805-0505
Musaddiq J. Awan
- Recruiting
Helen F Graham Cancer Center
Newark, Delaware, 19713
Site Public Contact, 302-623-4450, lbarone@christianacare.org
Gregory A. Masters
- Recruiting
Medical Oncology Hematology Consultants PA
Newark, Delaware, 19713
Site Public Contact, 302-623-4450, lbarone@christianacare.org
Gregory A. Masters
- Recruiting
Christiana Care Health System-Christiana Hospital
Newark, Delaware, 19718
Site Public Contact, 302-623-4450, lbarone@christianacare.org
Gregory A. Masters
- Recruiting
Cancer Care Center of O'Fallon
O'Fallon, Illinois, 62269
Site Public Contact, 217-876-4762, morganthaler.jodi@mhsil.com
Bryan A. Faller
- Recruiting
HSHS Saint Elizabeth's Hospital
O'Fallon, Illinois, 62269
Site Public Contact, 217-876-4762, morganthaler.jodi@mhsil.com
Bryan A. Faller
- Recruiting
Drexel Town Square Health Center
Oak Creek, Wisconsin, 53154
Site Public Contact, 414-805-0505
Musaddiq J. Awan
- Recruiting
Northwestern Medicine Orland Park
Orland Park, Illinois, 60462
Site Public Contact, nctnprogram_rhlccc@northwestern.edu
Laila A. Gharzai
- Recruiting
Illinois CancerCare-Ottawa Clinic
Ottawa, Illinois, 61350
Site Public Contact, 309-243-3605, andersonj@illinoiscancercare.com
Bryan A. Faller
- Recruiting
University of Kansas Cancer Center-Overland Park
Overland Park, Kansas, 66210
Site Public Contact, 913-588-3671, KUCC_Navigation@kumc.edu
Christopher Lominska
- Recruiting
University of Kansas Hospital-Indian Creek Campus
Overland Park, Kansas, 66211
Site Public Contact, 913-588-3671, KUCC_Navigation@kumc.edu
Christopher Lominska
- Recruiting
Illinois CancerCare-Pekin
Pekin, Illinois, 61554
Site Public Contact, 309-243-3605, andersonj@illinoiscancercare.com
Bryan A. Faller
- Recruiting
Illinois CancerCare-Peoria
Peoria, Illinois, 61615
Site Public Contact, 309-243-3605, andersonj@illinoiscancercare.com
Bryan A. Faller
- Recruiting
OSF Saint Francis Radiation Oncology at Peoria Cancer Center
Peoria, Illinois, 61615
Site Public Contact, 309-243-3605, andersonj@illinoiscancercare.com
Bryan A. Faller
- Recruiting
OSF Saint Francis Medical Center
Peoria, Illinois, 61637
Site Public Contact, 309-243-3605, andersonj@illinoiscancercare.com
Bryan A. Faller
- Recruiting
Illinois CancerCare-Peru
Peru, Illinois, 61354
Site Public Contact, 309-243-3605, andersonj@illinoiscancercare.com
Bryan A. Faller
- Recruiting
Illinois CancerCare-Princeton
Princeton, Illinois, 61356
Site Public Contact, 309-243-3605, andersonj@illinoiscancercare.com
Bryan A. Faller
- Recruiting
Aspirus Cancer Care-Rhinelander-James Beck Cancer Center
Rhinelander, Wisconsin, 54501
Site Public Contact, 715-847-2353, Beth.Knetter@aspirus.org
Andrew J. Huang
- Recruiting
Aspirus Cancer Care - Stevens Point
Stevens Point, Wisconsin, 54481
Site Public Contact, 715-847-2353, Beth.Knetter@aspirus.org
Andrew J. Huang
- Recruiting
Stony Brook University Medical Center
Stony Brook, New York, 11794
Site Public Contact, 800-862-2215
Achuta K. Guddati
- Recruiting
ProMedica Flower Hospital
Sylvania, Ohio, 43560
Site Public Contact, 419-824-1842, PCIOncResearch@promedica.org
Ahmed G. Elsayed
- Recruiting
ProMedica Toledo Hospital/Russell J Ebeid Children's Hospital
Toledo, Ohio, 43606
Site Public Contact, 419-824-1842, PCIOncResearch@promedica.org
Ahmed G. Elsayed
- Recruiting
University of Kansas Health System Saint Francis Campus
Topeka, Kansas, 66606
Site Public Contact, 785-295-8000
Christopher Lominska
- Recruiting
Illinois CancerCare - Washington
Washington, Illinois, 61571
Site Public Contact, 309-243-3605, andersonj@illinoiscancercare.com
Bryan A. Faller
- Recruiting
Aspirus Cancer Care-Wausau
Wausau, Wisconsin, 54401
Site Public Contact, 877-405-6866
Andrew J. Huang
- Recruiting
Froedtert West Bend Hospital/Kraemer Cancer Center
West Bend, Wisconsin, 53095
Site Public Contact, 414-805-0505
Musaddiq J. Awan
- Recruiting
University of Cincinnati Cancer Center-West Chester
West Chester, Ohio, 45069
Site Public Contact, 513-584-7698, cancer@uchealth.com
Kerri McGovern
- Recruiting
University of Kansas Hospital-Westwood Cancer Center
Westwood, Kansas, 66205
Site Public Contact, 913-588-3671, KUCC_Navigation@kumc.edu
Christopher Lominska
- Recruiting
Christiana Care Health System-Wilmington Hospital
Wilmington, Delaware, 19801
Site Public Contact, 302-623-4450, lbarone@christianacare.org
Gregory A. Masters
- Recruiting
Aspirus Cancer Care - Wisconsin Rapids
Wisconsin Rapids, Wisconsin, 54494
Site Public Contact, 715-422-7718
Andrew J. Huang
About this study
Official title: Radiotherapy With Concurrent Cetuximab vs. Carboplatin and Paclitaxel in Patients With Stage III-IVB Head and Neck Cancer With a Contraindication to Cisplatin: A Pragmatic Phase III Randomized Trial
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.
Read the detailed description
PRIMARY OBJECTIVE:
- To determine whether radiation therapy (RT) and concurrent carboplatin and paclitaxel (RT + carboplatin and paclitaxel [CP]) improves progression-free survival (PFS) compared to RT with concurrent cetuximab (RT + cetuximab [Cetux]) in patients with locoregionally advanced head and neck cancer (HNC) who have a contraindication to cisplatin.
SECONDARY OBJECTIVES:
- To compare overall survival (OS) between RT+CP versus (vs.) RT + Cetux. II. To compare PFS and OS by study arm within p16-negative and p16-positive subgroups.
III. To compare safety and toxicity of RT+CP vs. RT + Cetux. IV. To compare patterns of failure (locoregional and distant) and competing causes of death of RT+CP vs. RT + Cetux.
- To compare changes in diet, eating, and speech behaviors between RT+CP vs. RT + Cetux.
OUTLINE: Patients are randomized to 1 of 2 arms.
ARM 1: Patients undergo intensity modulated radiation therapy (IMRT) 5 days per week for 35 treatments. Starting within 7 days prior to radiation, patients receive a loading dose of cetuximab intravenously (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 computed tomography (CT) scan, positron emission tomography (PET) scan on study and blood sample collection throughout the study. Patients may undergo PET scan or magnetic resonance imaging (MRI) during screening.
ARM 2: 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.
After completion of study treatment, patients are followed up at 30 days and then 4, 6, 12, 18, 24, 30 and 36 months then annually thereafter.
- 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, Stage III Laryngeal Cancer AJCC v8
- Being tested
- Biospecimen Collection, Carboplatin, Cetuximab, Computed Tomography, Intensity-Modulated Radiation Therapy
- 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.
Biospecimen CollectionProcedure or surgery
Also called Biological Sample Collection, Biospecimen Collected, Specimen Collection
Undergo blood sample collection
CarboplatinDrug
Also called Blastocarb, Carboplat, Carboplatin Hexal, Carboplatino
Given IV
CetuximabBiological
Also called C 225, C-225, C225, Cetuximab Biosimilar CDP-1
Given IV
Computed TomographyProcedure or surgery
Also called CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography
Undergo CT scan
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
PaclitaxelDrug
Also called Anzatax, Asotax, Bristaxol, Praxel
Given IV
Positron Emission TomographyProcedure or surgery
Also called Medical Imaging, Positron Emission Tomography, PET, PET Scan, Positron emission tomography (procedure)
Undergo PET scan
Survey AdministrationOther
Ancillary studies
| Study group | Role | What they receive |
|---|---|---|
| Arm 1 (IMRT, cetuximab) | Experimental | 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. Receives: Procedure: Biospecimen Collection; Biological: Cetuximab; Procedure: Computed Tomography; Radiation: Intensity-Modulated Radiation Therapy; Procedure: Magnetic Resonance Imaging; Procedure: Positron Emission Tomography; Other: Survey Administration |
| Arm 2 (IMRT, carboplatin, paclitaxel) | Active comparator | 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. Receives: Procedure: Biospecimen Collection; Drug: Carboplatin; Procedure: Computed Tomography; Radiation: Intensity-Modulated Radiation Therapy; Procedure: Magnetic Resonance Imaging; Drug: Paclitaxel; Procedure: Positron Emission Tomography; Other: Survey Administration |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression free survival (PFS)
The PFS rates for each treatment arm will be estimated in the overall sample and within each p16 subgroup using the Kaplan-Meier method. Estimates of the median PFS and 2-year PFS rates will be obtained with 90% confidence intervals. The comparison of PFS distributions between each treatment arm will be performed using a one-sided stratified log-rank test (stratified by the randomization stratification factors). As additional analysis of treatment effect, multivariable analysis will be performed using a Cox proportional hazards model, where the stratification factors, and relevant patient and tumor characteristics are included (as measured by the model's Bayesian Information Criterion [BIC]). Hazard ratios and their respective 90% confidence intervals will be provided.
Measured: From randomization until locoregional failure, distant failure, or death due to any cause, up to 8 years
Secondary outcomes (9)
Overall survival (OS)
Will be summarized by treatment arm using standard Kaplan-Meier methods, where estimates of the median and 2-year OS will be obtained with 90% confidence intervals. The OS will be compared using a one-sided stratified log-rank test, stratified by the randomization strata.
Measured: From randomization until death due to any cause, up to 8 years
OS by p16 status
Assessments within p16 subgroups is to compare treatment arms within potentially clinically relevant subgroups. Within p16-negative and p16-positive subgroups, the OS will be summarized by study arm using standard Kaplan-Meier methods. The median OS and 2-year OS rates will be reported with 90% confidence intervals. Comparisons will be made using one-sided stratified log-rank tests. Multivariate Cox regression models will also be considered, where relevant covariates are selected based on the model's BIC.
Measured: From randomization until death due to any cause, up to 8 years
PFS by p16 status
PFS assessments within p16 subgroups is to compare treatment arms within potentially clinically relevant subgroups. Within p16-negative and p16-positive subgroups, the PFS will be summarized by study arm using standard Kaplan-Meier methods. The median PFS and 2-year PFS rates will be reported with 90% confidence intervals. Comparisons will be made using one-sided stratified log-rank tests. Multivariate Cox regression models will also be considered, where relevant covariates are selected based on the model's BIC. No adjustments will be made for multiplicity.
Measured: From randomization until locoregional failure, distant failure, or death due to any cause, up to 8 years
Incidence of adverse events
Adverse event grades will be assessed by Common Terminology Criteria for Adverse Events version 5.0. The overall (highest grade) adverse events will be summarized by treatment arm using frequencies and relative frequencies.
Measured: Up to 24 months from end of radiation therapy (RT)
Incidence of patient reported incidence of adverse events
Patient responses will be summarized by treatment arm and time point using frequencies and relative frequencies.
Measured: Up to 12 months from end of RT
Time to locoregional failure
Will compare patterns of failure and competing causes of death between treatment arms. The number and type of failures will be summarized by treatment arm using frequencies and relative frequencies. The time to failure will be summarized by treatment arm using the cumulative incidence method, where estimates of the 2-year failure rates will be obtained with 90% confidence intervals. Comparisons between treatment arms will be made using the stratified Gray's test.
Measured: From randomization until first evidence of local, regional disease progression or recurrence, or death from study cancer, up to 8 years
Time to distant failure
Will compare patterns of failure and competing causes of death between treatment arms. The number and type of failures will be summarized by treatment arm using frequencies and relative frequencies. The time to failure will be summarized by treatment arm using the cumulative incidence method, where estimates of the 2-year failure rates will be obtained with 90% confidence intervals. Comparisons between treatment arms will be made using the stratified Gray's test.
Measured: From randomization until first evidence of distant metastasis, up to 8 years
Time to competing mortality
Will compare patterns of failure and competing causes of death between treatment arms. The number and type of failures will be summarized by treatment arm using frequencies and relative frequencies. The time to failure will be summarized by treatment arm using the cumulative incidence method, where estimates of the 2-year failure rates will be obtained with 90% confidence intervals. Comparisons between treatment arms will be made using the stratified Gray's test.
Measured: From randomization until death due to other or unknown causes, up to 8 years
Longitudinal eating/speech profiles
Assessed via the Performance Status Scale for Head and Neck Cancer. The mean score change (relative to end of radiation treatment) for each of these subscales between arms will be compared at 12 months post-RT using a two-sample independent t-test with a two-sided significance level of 0.05. A Wilcoxon test will be used if normality assumption does not hold. Temporal trends and differences between arms at other time points will be assessed using mixed models with the following covariates: time, treatment arm and its interaction.
Measured: At baseline, end of treatment, 4, 6 and 12 months from end of RT
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Mar 2026
- Study start31 Jul 2026
- Primary completion30 Nov 2035 (estimated)
- Study completion30 Nov 2040 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Clinical Stage I HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8Studies of the same condition, open and under way.
- More trials run by NRG OncologyThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 454 participants (estimated)
Sponsor and investigators
- Lead sponsor
- NRG Oncology
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Loren K Mell, Principal investigator, NRG Oncology
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07441681
- Sponsor's protocol ID
- NRG-HN016
- Other IDs
- NCI-2026-00811, NRG-HN016, NRG-HN016, U10CA180868
- Status last verified
- Aug 2026
- First submitted
- 24 Feb 2026
- Last updated
- 17 Aug 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- 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.