SB-715992 in Treating Patients With Recurrent or Metastatic Head and Neck Cancer

Inclusion Criteria:

• Patients must have histologically or cytologically confirmed squamous cell carcinomaof the head and neck that is recurrent or metastatic; with the exception of thenasopharynx, all primary sites (including oral cavity, oropharynx, hypopharynx, andlarynx) will be eligible; MedDRA disease terms:

• Oral neoplasms NOS, 10031008

• Oropharyngeal cancer recurrent, 10031098

• Hypopharyngeal cancer recurrent, 10021044

• Laryngeal cancer recurrent, 10023828

• Maxillofacial sinus neoplasm, 10026956

• Head and neck, 90002024

• Patients may have had a maximum of one prior chemotherapy regimen for recurrent ormetastatic disease; patients may enter this study and receive SB-715992 as theirfirst-line therapy for recurrent and/or metastatic disease; prior platinum-basedchemotherapy delivered concurrently with radiotherapy, or prior platinum-basedinduction chemotherapy, is allowed; there must be at least a 4 week interval betweenany chemotherapy (6 weeks for nitrosoureas or mitomycin C), radiotherapy or surgeryand study enrollment; exceptions may be made however, for low dose,non-myelosuppressive radiotherapy - please contact the Principal Investigator (Dr. E.Winquist) PRIOR to registration if questions arise about the interpretation of thiscriterion; for patients who received local therapy prior to study entry, there must beeither progression of measurable disease documented within the treatment field, ormust have measurable disease outside the treatment field prior to study entry

• Patients must have measurable disease, defined as at least one lesion that can beaccurately measured in at least one dimension (longest diameter to be recorded) as >= 20 mm with conventional techniques or as >= 10 mm with spiral CT scan

• Life expectancy of greater than 12 weeks.

• ECOG performance status 0,1, or 2

• Leukocytes >= 3,000/uL

• Absolute neutrophil count >= 1,500/uL

• Platelets >= 100,000/uL

• Total bilirubin =< 1.5 X institutional upper limit of normal

• AST(SGOT)/ALT(SGPT) =< 3.0 X institutional upper limit of normal (=< 5.0 X if livermetastases)

• Creatinine =< 1.5 X institutional upper limit of normal

• Peripheral neuropathy may be no greater than grade 1

• Eligibility of patients receiving medications or substances known to affect, or withthe potential to affect the activity or pharmacokinetics of SB-715992 will bedetermined following review of their use by the TREATING RESPONSIBLE investigator;patients receiving nonprohibited medications or substances known to interact withCYP450 isoenzymes may be eligible but should be monitored carefully; questions abouteligibility related to concommitant use of medications should be discussed with thePrincipal Investigator

• HIV-positive patients receiving combination anti-retroviral therapy are excluded fromthe study

• Patients requiring oral anticoagulants (coumadin, warfarin) are eligible providedthere is increased vigilance with respect to monitoring INR. If medically appropriateand treatment available, the investigator may also consider switching these patientsto LMW heparin, where an interaction with SB-715992 is not expected

• 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 forthe duration of study participation; should a woman become pregnant or suspect she ispregnant while participating in this study, she should inform her treating physicianimmediately

• Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

• Patients with non-squamous cell carcinomas of the head and neck or nasopharyngealcancer

• Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks fornitrosoureas or mitomycin C) prior to entering the study or those who have notrecovered from AEs due to agents administered more than 4 weeks earlier

• Patients may not have received any other investigational agents within 28 days ofstudy entry

• Patients may not receive other anti-cancer therapy (cytotoxic, biologic, radiation, orhormonal other than for replacement) while on this study

• The following lists of medications/substances are moderate to significantinhibitors/inducers of CYP3A4 that, if administered concomitantly with SB-715992, mayalter study drug exposure; the use of these medications/substances within 14 days (>= 6 months for amiodarone) prior to the administration of the first dose of SB-715992through discontinuation from the study is prohibited

• Inhibitors of CYP3A4:

• Antibiotics: clarithromycin, erythromycin, troleandomycin

• Antifungals: itraconazole, ketoconazole, fluconazole (doses > 200 mg/day),voriconazole

• Antidepressants: nefazodone, fluovoxamine

• Calcium channel blockers: verapamil, diltiazem

• Miscellaneous: amiodarone*, grapefruit juice, bitter orange

• Use of amiodarone within 6 months prior to the administration of thefirst dose of SB-715992 is prohibited

• Inducers of CYP3A4:

• Anticonvulsants: phenytoin, carbamazepine, Phenobarbital, oxcarbazepine

• Antibiotics: rifampin, rifabutin, rifapentine

• Miscellaneous: St. John's wort, modafinil

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

• History of allergic reactions attributed to compounds of similar chemical or biologiccomposition to SB-715992

• Uncontrolled intercurrent illness including, but not limited to, ongoing or activeinfection, symptomatic congestive heart failure, unstable angina pectoris, cardiacarrhythmia, or psychiatric illness/social situations that would limit compliance withstudy requirements

• Pregnant women are excluded from this study because SB-715992 is a mitotic inhibitorwith the potential for teratogenic or abortifacient effects; because there is anunknown but potential risk for adverse events in nursing infants secondary totreatment of the mother with SB-715992, breastfeeding should be discontinued if themother is treated with SB-715992