Comparing Radiation Plus Cetuximab to Radiation Plus Chemotherapy in People With Head and Neck Cancer Who Cannot Receive Cisplatin
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
3 other identifiers
interventional
454
0 countries
N/A
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_3
Started Jan 2027
Longer than P75 for phase_3
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
February 24, 2026
CompletedFirst Posted
Study publicly available on registry
March 2, 2026
CompletedStudy Start
First participant enrolled
January 6, 2027
ExpectedPrimary Completion
Last participant's last visit for primary outcome
November 30, 2035
Study Completion
Last participant's last visit for all outcomes
November 30, 2035
May 4, 2026
April 1, 2026
8.9 years
February 24, 2026
April 28, 2026
Conditions
Outcome Measures
Primary Outcomes (1)
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.
From randomization until locoregional failure, distant failure, or death due to any cause, up to 8 years
Secondary Outcomes (9)
Overall survival (OS)
From randomization until death due to any cause, up to 8 years
OS by p16 status
From randomization until death due to any cause, up to 8 years
PFS by p16 status
From randomization until locoregional failure, distant failure, or death due to any cause, up to 8 years
Incidence of adverse events
Up to 24 months from end of radiation therapy (RT)
Incidence of patient reported incidence of adverse events
Up to 12 months from end of RT
- +4 more secondary outcomes
Other Outcomes (3)
Primary outcome treatment effect by sex
Up to 8 years
Primary treatment outcome by race
Up to 8 years
Primary treatment outcome by ethnicity
Up to 8 years
Study Arms (2)
Arm 1 (IMRT, cetuximab)
EXPERIMENTALPatients 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.
Arm 2 (IMRT, carboplatin, paclitaxel)
ACTIVE COMPARATORPatients 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
Undergo blood sample collection
Given IV
Given IV
Undergo CT scan
Undergo IMRT
Undergo MRI
Given IV
Undergo PET scan
Ancillary studies
Eligibility Criteria
You may qualify if:
- 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
- +25 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- NRG Oncologylead
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Loren K Mell
NRG Oncology
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
February 24, 2026
First Posted
March 2, 2026
Study Start (Estimated)
January 6, 2027
Primary Completion (Estimated)
November 30, 2035
Study Completion (Estimated)
November 30, 2035
Last Updated
May 4, 2026
Record last verified: 2026-04
Data Sharing
- IPD Sharing
- Will share
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.