Comparing Radiation Plus Cetuximab to Radiation Plus Chemotherapy in People With Head and Neck Cancer Who Cannot Receive Cisplatin

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.

PRIMARY OBJECTIVE: 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, 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.