A Phase IB Study Of Oral SCH 66336 Preoperatively In Patients With Head And Neck Squamous Cell Cancer

Inclusion criteria

• Histologically-confirmed stage II, III and IV squamous cell carcinoma of the head and neck.
• Patient's tumor is fully resectable and does not require radiotherapy to the entire buccal mucosa or patients who are to be treated with definitive radiation therapy as long as adequate (>2cm^3) of tissue can be obtained post-therapy with SCH66336.
• ECOG Performance Status of </= 2
• Laboratory values (performed within 14 days prior to administration of SCH 66336):

• White blood cell count greater than 3.0 x 10^9/L
• Platelet count greater than or equal to 150 x 10^9/L
• Hemoglobin greater than or equal to 10 gm/dL (100 gm/L). Patients may have received transfusions and/or erythropoietin to attain this value. However, they must have been stable without treatment for at least one week in order to be eligible.
• Serum creatinine less than 1.5 times the upper limit of normal.
• Total bilirubin less than 1.5 times the upper limit of normal.
• SGOT or SGPT (only one of these tests needs to be performed) less than or equal to 5.0 times upper limit of normal.
• Able to provide written informed consent.
• Negative pregnancy test (female patients of childbearing potential only), after signing informed consent and prior to registration.
• Patients may have received prior investigational therapy but at least 4 weeks must have elapsed with recovery from all toxicities.
• No more than two prior chemotherapy regimens for systemic disease.

Exclusion criteria

• Patients who are poor medical risks because of non-malignant systemic disease, as well as those with active uncontrolled infection.
• Uncontrolled heart disease (symptomatic ischemic heart disease or congestive heart failure, or either of these conditions with a variable medication requirement).
• Patients with QTc prolongation at baseline.
• Intractable vomiting (e.g., CTC Grade 2 or higher despite antiemetic medication) or any medical condition which could interfere with taking oral medication and gastrointestinal absorption.
• Patient has received prior induction chemotherapy.
• Patient exhibits confusion, disorientation, or has a history of major psychiatric illness which may impair patient's understanding of the informed consent.
• Prior therapy with a FPT inhibitor.
• Patient's life expectancy is less than 6 months.
• Patient has grade 3 or 4 neurotoxicity from previous anticancer treatment or significant neuropathy from any cause.
• Patient requires total parenteral nutrition with lipids.
• Chemotherapy, radiation therapy, biologic therapy, or surgery within four weeks prior to administration of SCH 66336. Nitrosourea or mitomycin C administration within 6 weeks of SCH 66336.
• Lack of resolution of all toxic manifestations of prior chemotherapy, biologic or radiation therapy.
• Radiation therapy to greater than 30% of bone marrow as defined in Appendix D. (Whole pelvic radiation alone is not exclusionary.)
• Known HIV positivity or AIDS-related illness.
• Pregnancy or lactation.
• Men or women of childbearing potential who are not using an effective method of contraception. Use of oral contraception or other hormonal modalities by the patient is not permitted.