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Comparing Radiation Plus Cetuximab to Radiation Plus Chemotherapy in People with Advanced Head and Neck Cancer Who Cannot Receive Cisplatin
Trial Status: active
This phase III trial compares cetuximab to chemotherapy, carboplatin and paclitaxel, with intensity modulated radiation therapy for the treatment of patients with head and neck cancer that may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced) 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 cetuximab or chemotherapy, with intensity modulated radiation therapy works best for the treatment of patients with advanced head and neck cancer who are unable to receive cisplatin.
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
Study sponsor and potential other locations can be found on ClinicalTrials.gov for NCT07441681.
I. 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:
I. 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.
V. 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, magnetic resonance imaging (MRI), or positron emission tomography (PET)/CT during screening, blood sample collection throughout the study, and fludeoxyglucose F-18 (FDG) PET/CT during follow-up.
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, MRI, or PET/CT during screening, blood sample collection throughout the study, and FDG PET/CT during follow-up.
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.
