Radiation plus cetuximab vs radiation plus chemotherapy for advanced head and neck cancer patients who cannot receive cisplatin

Is this trial a fit for you?

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

What this trial studies

In this phase 3 trial, adults with locally advanced head and neck squamous cell carcinomas (larynx, hypopharynx, oral cavity, or oropharynx) who cannot receive cisplatin are randomized to receive either concurrent cetuximab with IMRT or concurrent carboplatin and paclitaxel with IMRT. The study aims to compare progression-free survival as the primary outcome, with secondary measures including overall survival, safety, patterns of failure, and patient-reported changes in diet, eating, and speech. Eligibility requires verified tumor type and stage and tumor p16 status for oropharyngeal cancers. Treatments involve six weeks of IMRT with weekly cycles, plus targeted or chemotherapy agents during radiation. Imaging and biospecimen collection are part of the protocol for monitoring response and safety.

Why it matters

Who can join: the full rules

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) 9th edition stage III-IVB

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

      * AJCC 9th Edition TNM: T3 N0 or T1-3 N1 M0; AJCC 9th Edition Stage: III
      * AJCC 9th Edition TNM: T1-3 N2 or T4a N0-N2 M0; AJCC 9th Edition Stage: IVA
      * AJCC 9th Edition TNM: T4b N0-N2 or T1-4b N3 M0; AJCC 9th Edition Stage: IVB
  * p16-positive oropharynx cancer: AJCC 9th edition stage II-III

    * Eligible p16-Positive Oropharyngeal Primaries

      * AJCC 9th Edition TNM: T3 N0-2 or T1-2 N2 M0; AJCC 9th Edition Stage: II
      * AJCC 9th Edition TNM: T4 N0-3 or T1-3 N3 M0; AJCC 9th Edition Stage: III
* 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

Where it's running

• University of Alabama at Birmingham Cancer Center
  Birmingham, Alabama, United States Recruiting
• Kaiser Permanente-Anaheim
  Anaheim, California, United States Recruiting
• Kaiser Permanente-Baldwin Park
  Baldwin Park, California, United States Recruiting
• Kaiser Permanente-Bellflower
  Bellflower, California, United States Recruiting
• Tower Cancer Research Foundation
  Beverly Hills, California, United States Recruiting
• Kaiser Permanente-Fontana
  Fontana, California, United States Recruiting

+100 more sites. See ClinicalTrials.gov for the full list.

Study contacts

• Principal investigator: Loren K Mell — NRG Oncology

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Other studies for the same condition or treatment. Recruiting studies are listed first.

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How to take part

1. Review the eligibility criteria above with your treating physician.
2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.