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 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 direct 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 agree to use adequate contraception (hormonal or barrier method of birth control; 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.
National Institutes of Health Clinical Center
Bethesda, Maryland 20892. Last update: 09/16/2008