Phase II Trial of Nelfinavir With Concurrent Chemoradiotherapy in Squamous Cell Carcinoma of the Head and Neck
Condition: Head and Neck Squamous Cell Carcinoma
MeSH terms: Carcinoma; Carcinoma, Squamous Cell; Squamous Cell Carcinoma of Head and Neck
Intervention: Nelfinavir (Viracept®) 1250 mg; Chemoradiation
Intervention description: Period 1: Nelfinavir Lead-In (1250 mg bid, 7-14 days).; Period 2: Concurrent Chemoradiation (70 Gy over 7 weeks) with Nelfinavir (1250 mg bid)
Intervention MeSH terms: Nelfinavir
Phase: Phase 2
Study type: Interventional
Primary purpose: Diagnostic
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 18.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This is a Phase II trial of definitive chemoradiotherapy (CTRT) given with the protease
      inhibitor,Nelfinavir (NFV), in patients with locally advanced head and neck. Eligible
      patients will receive a "lead-in" period of Nelfinavir (1250 mg po bid) for 7-14 days prior
      to initiation of CTRT. Nelfinavir will then be given concurrently with platinum-based
      chemotherapy and radiation therapy (planned total dose of 70 Gy over 7 weeks).
    

Eligibility criteria:

        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 FMISO 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 FMISO.

          -  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.