This is a multi-center randomized phase iii study comparing the standard treatment of surgery followed by radiation therapy to surgery followed by radiation therapy and cetuximab concurrently to see if radiation therapy and cetuximab are better at treating locally advanced resected head and neck cancer. about 15patients will take part in this study at uT Southwestern, Parkland Health and Hospital System, and Richardson Regional Cancer Center. The treatment period will last for either 6 weeks or 11 weeks depending on which treatment arm the patient receives and the follow-up portion of the study is lifetime. This study is taking place at a number of other medical facilities around the country. There will be a total of 700 people participating in the research study throughout the united States and/or other countries.
if the patient has met all the eligibility criteria, they will be registered to the study and randomized to one of two arms:
arm 1: (Radiation Therapy alone) Patients will receive 2 Gy/day in 30 fractions for a total of 60 Gy
arm 2: (Radiation Therapy Plus Weekly Cetuximab) at least 5 days prior to radiation therapy patients will receive an initial dose of Cetuximab 400 mg/m2. no radiation will be given this day and the day of the loading dose is not included in these 5 days. Patients will then receive radiation therapy at 2 Gy/day in 30 fractions for a total of 60 Gy plus cetuximab 250 mg./m2/week for 6 weeks. Cetuximab will be given on a Monday or Tuesday. Patients will then receive cetuximab 250 mg/m2 on a weekly schedule after the completion of radiation therapy for a total of 4 additional doses.
Pathologically (histologically) proven diagnosis of squamous cell carcinoma (including variants such as verrucous carcinoma, spindle cell carcinoma, carcinoma NOS, etc.) of the head/neck (oral cavity, oropharynx or larynx); Note: Hypopharynx primaries are excluded because these patients have both a poor prognosis and high likelihood of post-radiation complications.
3.1.2 Clinical stage T1, N1-2 or T2- T4a, N0-2, M0 including no distant metastases, based upon the following minimum diagnostic workup:
General history and physical examination by a Radiation Oncologist and/or Medical Oncologist within 8 weeks prior to registration;
Examination by an ENT or Head & Neck Surgeon, within 8 weeks prior to registration; a laryngopharyngoscopy (mirror and/or fiberoptic and/or direct procedure) is recommended but not required.
Chest x-ray (at a minimum) or chest CT scan (with or without contrast) or CT/PET of chest (with or without contrast) within 8 weeks prior to registration.
3.1.3 Gross total resection of the primary tumor with curative intent must be completed within 7 weeks of registration with surgical pathology demonstrating one or more of the following intermediate
* risk factors:
Single lymph node > 3 cm or >= 2 lymph nodes (all < 6 cm) [no extracapsular extension];
Close margin(s) of resection, defined as cancer extending to within 5 mm of a surgical margin, and/or an initially focally positive margin that is subsequently superseded by intraoperative negative margins. Similarly, patients whose tumors had focally positive margins in the main specimen but negative margins from re-excised samples in the region of the positive margin are eligible. For questions or ambiguities about an individual case, contact Dr. Machtay and/or Dr. Holsinger prior to enrolling the patient.
Pathologically confirmed T3 or T4a primary tumor; For questions or ambiguities about an individual case, contact Dr. Machtay and/or Dr. Holsinger prior to enrolling the patient.
T2 oral cavity cancer with > 5 mm depth of invasion.
3.1.4 Zubrod Performance Status of 0-1 within 2 weeks prior to registration;
3.1.5 Age >= 18;
3.1.6 CBC/differential obtained within 4 weeks prior to registration on study, with adequate bone marrow function defined as follows:
Absolute granulocyte count (AGC) >= 1,500 cells/mm3;
Platelets >= 100,000 cells/mm3;
Hemoglobin >= 8.0 g/dl (Note: The use of transfusion or other intervention to achieve Hgb >=
8.0 g/dl is acceptable).
3.1.7 Adequate hepatic function, defined as follows:
Total bilirubin < 2 x institutional ULN within 2 weeks prior to registration;
AST or ALT < 3 x institutional ULN within 2 weeks prior to registration.
3.1.8 Adequate renal function, defined as follows:
Serum creatinine < 2 x institutional ULN within 2 weeks prior to registration or;
creatinine clearance (CC) >= 50 ml/min within 2 weeks prior to registration determined by 24-
hour collection or estimated by Cockcroft-Gault formula: CCr male = [(140 x age) x (wt in kg)] [(Serum Cr mg/dl) x (72)] CCr female = 0.85 x (CrCl male)
3.1.9 Negative serum pregnancy test within 2 weeks prior to registration for women of childbearing
3.1.10 (6/4/10) The following assessments are required within 2 weeks prior to the start of registration:
Na, K, Cl, glucose, Ca, Mg, and albumin. Note: Patients with an initial magnesium < 0.5 mmol/L (1.2 mg/dl) may receive corrective magnesium supplementation but should continue to receive either prophylactic weekly infusion of magnesium and/or oral magnesium supplementation (e.g., magnesium oxide) at the investigator[Single Quote]s discretion.
3.1.11 Women of childbearing potential and male participants who are sexually active must agree to
use a medically effective means of birth control;
3.1.12 Patients must provide study specific informed consent prior to study entry, including consent for
mandatory tissue submission for EGFR and for oropharyngeal patients, HPV analyses.