Cetuximab and Radiation Therapy in Treating Patients With Stage III-IV Head and Neck Cancer

PRIMARY OBJECTIVES:

I. 2 year (yr) locoregional control in cetuximab responders.

SECONDARY OBJECTIVES:

I. Assess secondary clinical endpoints such as the percent of patients receiving neoadjuvant
cetuximab who progress by computed tomography (CT) Response Evaluation Criteria in Solid
Tumors (RECIST) 1.1 criteria during the neoadjuvant cetuximab, the 2 yr locoregional control
for non-responders to neoadjuvant cetuximab, and the complete response rate to positron
emission tomography (PET)/computed tomography (CT) scan 3 months after the completion of
radiation therapy for both responders and for non-responders to neoadjuvant cetuximab.

II. Analyze the relationship of known deoxyribonucleic acid (DNA) mutations in tumor per the
FoundationOne genomic profile, and correlate to clinical endpoints such as locoregional
control.

II. Analyze any changes in protein production at the tumor in response to 3 weeks of
cetuximab.

III. Analyze any changes in protein production at the skin in response to 3 weeks of
cetuximab.

IV. To investigate whether the tumor imaging characteristics including anatomical and
molecular parameters evaluated by PET/CT, either alone or combined with other biomarkers can
attribute to the better prediction for the clinical outcomes, as the response to neoadjuvant
cetuximab; and the final clinical endpoint, the 2-year local regional controls.

OUTLINE:

Patients receive cetuximab intravenously (IV) over 60-120 minutes for 3 weeks. Patients then
undergo external beam radiation therapy (EBRT) over 6-7 weeks. Patients achieving response
continue weekly doses of cetuximab until radiation therapy is completed. Patients unable to
achieve response or progression receive cisplatin IV over 1-2 hours on days 1, 22, and 43 of
radiation therapy.

After completion of study treatment, patients are followed up every 3 months for 2 years.

Inclusion Criteria:

- Histologically proven squamous cell carcinoma of the oropharynx, hypopharynx or larynx

- Stage III/IVa/b squamous cell carcinoma (SCC) by American Joint Committee on Cancer
(AJCC) 7 criteria (advanced, but not metastatic)

- Patients must give informed consent

- Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status =<
2

- Platelets >= 100,000/uL

- Absolute neutrophil count (ANC) >= 1,500/uL

- Hemoglobin > 8 g/dl (use of transfusion to achieve this is acceptable)

- Total bilirubin < 2 X institutional upper limit of normal (ULN)

- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase
[SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT])
=< 3 X institutional ULN

- Serum creatinine < 2 x institutional ULN or creatinine clearance > 50 ml/min as
determined by 24 hour collection or estimated by Cockcroft-Gault formula

- Estimated life expectancy of at least 12 weeks

- Negative pregnancy test

Exclusion Criteria:

- Patients may not have received previous therapy for their head and neck SCC, including
chemotherapy, radiation therapy, or surgery beyond biopsy

- Second primary malignancy; exceptions are 1) patient had a second primary malignancy
but has been treated and disease free for at least 3 years, 2) in situ carcinoma (e.g.
in situ carcinoma of the cervix), 3) non-melanomatous carcinoma of the skin

- Patients with metastatic disease beyond the neck and supraclavicular region will be
excluded

- Serious concomitant systemic disorders (including active infections) that would
compromise the safety of the patient or compromise the patient's ability to complete
the study, at the discretion of the investigator; this includes scleroderma

- History of allergic reactions attributed to compounds of similar chemical or biologic
composition to cetuximab or cisplatinum or other agents used in the study

- Women who are pregnant; women of childbearing age must agree to undergo a pregnancy
test prior to therapy and to use adequate contraception (hormonal or barrier method of
birth control; abstinence) prior to study entry, for the duration of study
participation and for 6 months after; should a woman become pregnant or suspect she is
pregnant while participating in this study, she should inform her treating physician
immediately

- Patients with human immunodeficiency virus (HIV) infection are not automatically
excluded, but must meet the following criteria: cluster of differentiation (CD)4 count
is > 499/cu mm and their viral load is < 50 copies/ml; use of highly active
anti-retroviral therapy (HAART) is allowed

- Patients who have had either myocardial infarction, coronary artery bypass graft,
coronary artery stenting, hospital admission for heart related issues such as
congestive heart failure or arrhythmia within the last 3 months, will not be allowed
on protocol

- Grade 3-4 electrolyte abnormalities (Common Terminology Criteria for Adverse Events
[CTCAE], version [v]. 4):

- 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