A Phase II Trial of a Protease Inhibitor, Nelfinavir (NFV), Given With Definitive, Concurrent Chemoradiotherapy (CTRT) in Patients With Locally-Advanced, Human Papilloma Virus (HPV) Negative, Squamous Cell Carcinoma of the Head and Neck

Inclusion Criteria:

- Patients ≥ 18 years old.

- Histologically confirmed diagnosis of squamous cell carcinoma of the oral cavity,
oropharynx, larynx, or hypopharynx stages III, IVa, or IVb, p16-negative on
immunohistochemistry

- Determined by the treating physician to be a candidate for organ preserving,
concurrent standard chemotherapy and radiation therapy to the head and neck with
definitive intent.

- ECOG Performance Status 0-2

- Patients must sign an informed consent document that indicates they are aware of the
investigational nature of the treatment in this protocol as well as the potential
risks and benefits.

- The effects of EF5 on the developing human fetus are unknown. For this reason, women
of childbearing potential and men must agree to use adequate contraception (hormonal
or barrier method of birth control) prior to study entry, during study, until 1 month
after completion of the final 18F-EF5 PET/CT scan. Should a woman become pregnant or
suspect she is pregnant while participating in this study, she should inform her
treating physician immediately. Serum pregnancy testing will be required for women of
childbearing potential.

- Ability to understand and the willingness to sign a written informed consent.

Exclusion Criteria

- Prior radiation therapy to the head and neck

- Prior chemotherapy within the past 5 years

- Previous therapy with a human immunodeficiency virus (HIV) protease inhibitor

- Pregnant or lactating patients.

- Patients with known HIV disease. These patients have a high probability of treatment
with anti-retroviral therapy which may interact with the nelfinavir.

- Absolute Neutrophil Count ≤ 1500 per mm3

- Platelet count ≤ 100,000 per mm3

- Serum creatinine > 1.5 times the upper limit of normal

- Serum AST or ALT > 2 times the upper limit of normal

- Serum bilirubin > 1.2 mg/dl

- Weight loss of > 10% over the past 6 months which is due to tumor wasting syndrome

- Distant metastases

- Patients receiving the following drugs that are contraindicated with NFV will be
excluded: Antiarrhythmics:amiodarone, quinidine, Antimycobacterial: rifampin, Ergot
Derivatives:dihydroergotamine, ergonovine, ergotamine, methylergonovine, Herbal
Products: St.John's wort (hypericum perforatum), HMG-CoA Reductase Inhibitors:
lovastatin,simvastatin, Neuroleptic:pimozide, Proton Pump Inhibitors,
Sedative/Hypnotics: midazolam, triazolam,

- Patients receiving the following drugs will be clinically evaluated as to whether
dosage/medication can be changed to permit patient on study: Anti-Convulsants:
carbamazepine, Phenobarbital, Anti-Convulsant:phenytoin, Anti-Mycobacterial:rifabutin,
PDE5 Inhibitors: sildenafil, vardenafil, tadalafil, HMG-CoA: Reductase Inhibitors:
atorvastatin, rosuvastatin, Immuno-suppressants: cyclosporine,tacrolimus, sirolimus,
Narcotic Analgesic: methadone, Oral Contraceptive:ethinyl estradiol, Macrolide
Antibiotic:azithromycin, Inhaled/nasal steroid fluticasone, Antidepressant: trazodone.

- Women of childbearing potential who have a positive result on screening urine
pregnancy test.

- Subjects with moderate-severe renal disease.

- History of allergic reactionsattributed to Flagyl (metronidazole), which has a
chemical structure similar to EF5.

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