Inclusion Criteria:

- First stage Patients with AJCC 7th edition stage IVA-IVC or recurrent or metastatic
head and neck cancer will be eligible. Patients with M1 disease must have
asymptomatic or low volume distant metastasis and require palliation for local and
regional disease.

- Second stage (phase II part) Patients with AJCC 7th edition stage III-IVB (T1-T4,
N1-3M0) head and neck cancer, except WHO type II and III nasopharyngeal cancer,
including unknown primary tumors.

- Histologically or cytologically confirmed diagnosis of squamous cell carcinoma or
variants or poorly differentiated carcinoma.

- Unidimensionally measurable disease (RECIST criteria).

- ECOG performance status of 0-2

- In the second stage of the study, therapy will be administered with a curative intent
and patients should not have recurrent disease or distant metastasis.

- Primary tumor and/or lymphadenopathy should be technically suitable for intratumoral
injections. The Otolaryngologist specialist on the head and neck team will determine
this feasibility.

- Participating patients should agree to undergo a tumor biopsy at baseline as well as
approximately 2 weeks later as specified in study schema.

- Prior treatment

- First stage: any prior treatment, except prior therapy, which specifically and
directly targets the EGFR pathway, administered within the last 6 months.

- Second stage: no prior chemotherapy, biologic/molecular targeted therapy (including
any prior therapy which specifically and directly targets the EGFR pathway), or
radiotherapy for head and neck cancer.

- Prior surgical therapy will consist only of incisional or excisional biopsy,
including tonsillectomy, and organ sparing procedures, including neck dissection. Any
non-biopsy surgical procedure for head and neck cancer must have taken place < 3
months of initiating protocol treatment.

- Patients must have organ and marrow function as defined below:

Absolute neutrophil count above/equal to 1,000/µL Platelets above/equal to 75,000/µL
Hemoglobin above/ equal to 10 g/dL Total bilirubin <2 x upper normal institutional limits
Creatinine clearance > 20 mL/min

- Age 18 years or older

- Because radiation therapy is known to be teratogenic and EFGR inhibitors may have
teratogenic potential, women of childbearing 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, and for 3 months after completing
study treatment. Should a woman become pregnant or suspect she is pregnant while
participating in this study, she should inform her treating physician immediately.

- 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.

Exclusion Criteria:

- Severe renal insufficiency (creatinine clearance < 20 mL/min)

- Treatment with anticoagulants, except when used to maintain the patency of a central
venous line, or INR >1.5, or PTT ratio >1.5.

- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection or psychiatric illness/social situations that would limit compliance with
study requirements. Significant history of uncontrolled cardiac disease; i.e.,
uncontrolled hypertension, unstable angina, uncontrolled congestive heart failure.

- Patients may not be receiving any other investigational agents.

- No history of prior malignancy, with the exception of curatively treated squamous
cell or basal carcinoma of the skin or in situ cervical cancer, DCIS or LCIS of the
breast, localized early stage prostate cancer, or malignancy that has been treated
with a curative intent with a 3-year disease-free survival.

- Pregnant women are excluded from this study because cetuximab, EGFR AS, and radiation
have the potential for teratogenic or abortifacient effects. Because there is an
unknown but potential risk for adverse events in nursing infants secondary to
treatment of the mother with cetuximab and EGFR AS, breastfeeding should be
discontinued if the mother is treated with cetuximab. The effects of cetuximab and
EGFR AS on the developing human fetus at the recommended therapeutic dose are
unknown. For this reason 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.

- HIV-positive patients receiving combination anti-retroviral therapy are excluded from
the study because of possible drug interactions with cetuximab. Appropriate studies
will be undertaken in patients receiving combination anti-retroviral therapy when
indicated. HIV status of the patient will be obtained from the patient's history via
discussion with the investigator. HIV testing is not required.

- Prior severe infusion reaction to a monoclonal antibody.

- Patients who are not informed of and are not willing to comply with the
investigational nature of the study and have not signed a written informed consent in
accordance with institutional and good clinical practice guidelines.

- Phase 2 ONLY (second stage) - Subjects M1 disease will be excluded.