- Pathologically confirmed squamous cell carcinoma, undifferentiated carcinoma, or
poorly differentiated carcinoma of the oropharynx, larynx, or hypopharynx with no
evidence of distant metastasis. Biopsy sampling of primary tumor with pathology
report documenting diagnostic tissue type is required.
- Patients must have stage III, IVa or IVb disease as determined by imaging studies and
complete head and neck exam. Staging evaluation should be in accordance with the
American Joint Committee on Cancer Staging Manual, 7th edition.
- Patients with oropharyngeal squamous cell carcinoma may have p16(+) or p16(-)
disease; in these patients, p16 status must be known prior to randomization.
Assessment of p16 status may occur locally or centrally. Note: The definition of
p16(+) disease is diffuse nuclear and cytoplasmic staining in 70% of tumor cells.
- Patients must be untreated with curative-intent surgery for current diagnosis of
Stage III, IVa, or IVb disease. Diagnostic biopsy of primary tumor and/or nodal sites
- Diagnostic simple tonsillectomy is permitted, provided patient has RECIST-measurable
residual tumor and/or nodal disease.
- Patients with a second HNSCC primary tumor are eligible for this study, provided more
than 2 years have elapsed since the first diagnosis of HNSCC, the original tumor was
managed with surgery only (no adjuvant chemotherapy/radiotherapy), and has not
- Patients with simultaneous primaries or bilateral tumors are excluded, with the
exception of patients with bilateral tonsil cancers or patients with T1-2, N0, M0
resected differentiated thyroid carcinoma, who are eligible.
- No prior systemic treatment (chemotherapy or biologic/molecular targeted therapy) or
radiation treatment for head and neck cancer.
- Patients may have received chemotherapy or radiation for a previous, curatively
treated non-HNSCC malignancy, provided at least 2 years have elapsed.
- Patients must be untreated with radiation above the clavicles.
- Patients with a history of curatively-treated non-HNSCC malignancy must be
disease-free for at least 2 years except for carcinoma-in-situ of cervix,
non-melanomatous skin cancer, or T1-2, N0, M0 resected differentiated thyroid
- Diagnostic primary tumor tissue must be available for ERCC1 staining
- Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1 (See Appendix 8)
- Age 18
- Patients must have measurable disease according to RECIST 1.1
- Patients must have the following laboratory values measured within 14 days of
- Absolute neutrophil count (ANC) > 1500/mm3
- Hemoglobin (Hb) > 8.0 g/dL
- Platelet count (PLT) > 100,000/mm3
- Creatinine clearance 45 ml/min determined by 24-hour collection or estimated by the
Calculated Creatinine Clearance = [(140-age) X (actual body weight in kg) X (0.85 if
female)]/(72 X serum creatinine)
- Serum bilirubin < 2 mg/dL
- AST (aspartate aminotransferase) and ALT (alanine aminotransferase) < 3 times upper
limit of normal (ULN)
- The following assessments are required within 14 days prior to registration: Na, K,
Cl, glucose, Ca, Mg, and albumin. The following metabolic values will exclude
patients from study enrollment:
- Serum calcium (ionized or adjusted for albumin) < 7 mg/dl (1.75 mmol/L) or > 12.5
mg/dl (> 3.1 mmol/L) despite intervention to normalize levels
- Magnesium < 0.9 mg/dl (< 0.4 mmol/L) or > 3 mg/dl (> 1.23 mmol/L) despite
intervention to normalize levels
- Potassium < 3.5 mmol/L or > 6 mmol/L despite intervention to normalize levels
- Sodium < 130 mmol/L or > 155 mmol/L despite intervention to normalize levels 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 (eg, magnesium oxide) at
the investigator's discretion.
- No prior severe infusion reaction to a monoclonal antibody
- Written informed consent must be obtained from all patients prior to beginning
therapy. Patients should have the ability to understand and the willingness to sign a
written informed consent document.
- Informed consent must be obtained from all patients prior to beginning therapy,
including consent for mandatory tissue submission for ERCC1 staining (and p16
staining if not locally conducted). Patients should have the ability to understand
and the willingness to sign a written informed consent document.
- No unstable angina or myocardial infarction within the prior 6 months; no symptomatic
congestive heart failure; no serious cardiac arrhythmia requiring medication; no
cerebrovascular ischemia or stroke within the past 6 months.
- No uncontrolled intercurrent illness including active infection, uncontrolled
diabetes, uncontrolled hypertension, or uncontrolled psychiatric illness which in the
investigator's opinion would limit compliance with study requirements or compromise
- Women must not be pregnant or breast feeding because chemotherapy and/or cetuximab
may be harmful to the fetus or the nursing infant. Pregnant women are excluded from
this study because chemotherapy and/or cetuximab have the potential for teratogenic
or abortifacient effects.
- Women of child-bearing potential and men must agree to use adequate contraception
(hormonal or barrier method of birth control) prior to study entry and for the
duration of study participation. Should a woman become pregnant or suspect she is
pregnant while in this study, she should inform her treating physician immediately.
All females of childbearing potential must have a blood test or urine study within 14
days of registration to rule out pregnancy.
- HIV-positive patients receiving combination anti-retroviral therapy are excluded from
the study because of possible drug interactions with study drugs. Appropriate studies
will be undertaken in patients receiving combination anti-retroviral therapy when
indicated. Note: HIV testing is not required for entry into this protocol.
- Patients may not be receiving any other anti-neoplastic investigational agents.
Minimum Eligible Age: 18 Years
Maximum Eligible Age: N/A
Eligible Gender: Both