Inclusion Criteria

-INCLUSION CRITERIA:

1. Histologically or cytologically confirmed squamous cell carcinoma, including
variants, or undifferentiated/poorly differentiated carcinoma of the head and neck
(any site, except nasopharynx).

2. Previously untreated stage IV disease (AJCC staging system, 6th edition), or,

3. Patients with residual disease or regional recurrence of head and neck cancer after
surgery and/or chemotherapy, but with no prior bortezomib, EGFR inhibitor therapy or
head and neck radiotherapy. All such patients should be eligible to receive full dose
radiation therapy, and must be evaluated and accepted for treatment by a Radiation
Oncologist. Prior cisplatin is allowed if administered greater than 3 months earlier.

4. Patients with no clinically measurable distant disease, or those with asymptomatic
small distant lesions outside the radiation field of less than or equal to 3cm
individual or aggregate diameter, but for whom palliation of local and regional
disease is clinically warranted will be eligible.

5. Any number of other prior systemic therapies is allowed. Patients must have fully
recovered from the effects of any prior surgery, or chemotherapy. A minimum time
period of 4 weeks (6 weeks for nitrosoureas or mitomycin C) should elapse between the
completion of prior chemotherapy and enrollment in the study.

6. Age greater than or equal to 18 years. Because no dosing or adverse event data are
currently available on the use of bortezomib in combination with cetuximab or
cisplatin and radiation in patients < 18 years of age, and head and neck cancer in
children is exceedingly rare, except for those with disorders of DNA damage repair,
bone marrow or transplant immunosuppression likely to have lower tolerance to these
drugs and RT, children are excluded from this study.

7. ECOG performance status 0-1 (Karnofsky greater than or equal to 70 percent).

8. Patients must have normal organ and marrow function as defined below:

- absolute neutrophil count greater than or equal to 1,500/mcL

- platelets greater than or equal to 100,000/mcL

- total bilirubin within normal institutional limits, except for patients with
Gilberts syndrome, with increased indirect bilirubin less than or equal to 3
mg/dL

- AST(SGOT)/ALT(SGPT) less than or equal to 2.5 times institutional upper limit of
normal

- creatinine within normal institutional limits

OR

-creatinine clearance greater than or equal to 60 mL/min/1.73 m(2) for patients with
creatinine levels above institutional normal.

9. The effects of bortezomib on the developing human fetus are unknown. For this reason
and because other therapeutic agents used in this trial are known to be teratogenic,
women of child-bearing potential and men must have agreed to use adequate
contraception (hormonal or barrier method of birth control; prior vasectomy; tubal
ligation or abstinence) prior to study entry and for the duration of study
participation. Should a woman become pregnant or suspect she is pregnant while
participating in this study, she should inform her treating physician immediately.

10. Adequate cognitive and neurologic function to protect against and detect and report
toxicities experienced, and to understand and to sign a written informed consent
document.

EXCLUSION CRITERIA:

1. Patients with previously untreated nasopharyngeal cancer (any stage) will be
excluded, but patients with recurrent nasopharyngeal carcinoma will be eligible.

2. Prior treatment with radiation to the head and neck, or systemic EGFR inhibitors or
bortezomib is not allowed.

3. Patients who have had chemotherapy within 4 weeks (6 weeks for nitrosoureas or
mitomycin C) prior to entering the study or those who have not recovered from adverse
events due to agents administered more than 4 weeks earlier.

4. Patients may not be receiving any other investigational agents.

5. Patients with known brain metastases should be excluded from this clinical trial
because of their poor prognosis and because they often develop progressive neurologic
dysfunction that would confound the evaluation of neurologic and other adverse
events.

6. History of allergic reactions attributed to compounds of similar chemical or biologic
composition to bortezomib, cetuximab, cisplatin or other agents used in study.

7. Patients with greater than or equal to grade 2 peripheral sensory neuropathy because
bortezomib can cause irreversible worsening and a painful type of chemotherapy
associated peripheral neuropathy.

8. Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia, or psychiatric illness/social situations that would limit compliance with
study requirements.

9. Pregnant women are excluded from this study because bortezomib, cetuximab and
cisplatin 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 bortezomib, cetuximab and cisplatin, breastfeeding
should be discontinued if the mother is treated with bortezomib, cetuximab and
cisplatin. These potential risks may also apply to other agents used in this study.

10. HIV-positive patients or patients on any antiretroviral therapy are ineligible
because of the potential for possible pharmacodynamic interactions with bortezomib,
cetuximab and cisplatin, particularly bone marrow and mucosal toxicity, which could
affect the MTD. These patients are at increased risk of lethal infections when
treated with marrow-suppressive therapy.