A Phase 2 Study of SB-715992 in Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck

Inclusion Criteria:

- Patients must have histologically or cytologically confirmed squamous cell carcinoma
of the head and neck that is recurrent or metastatic; with the exception of the
nasopharynx, all primary sites (including oral cavity, oropharynx, hypopharynx, and
larynx) 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 or
metastatic disease; patients may enter this study and receive SB-715992 as their
first-line therapy for recurrent and/or metastatic disease; prior platinum-based
chemotherapy delivered concurrently with radiotherapy, or prior platinum-based
induction chemotherapy, is allowed; there must be at least a 4 week interval between
any chemotherapy (6 weeks for nitrosoureas or mitomycin C), radiotherapy or surgery
and 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 this
criterion; for patients who received local therapy prior to study entry, there must
be either progression of measurable disease documented within the treatment field, or
must have measurable disease outside the treatment field prior to study entry

- Patients must have measurable disease, defined as at least one lesion that can be
accurately 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 liver
metastases)

- 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 with
the potential to affect the activity or pharmacokinetics of SB-715992 will be
determined following review of their use by the TREATING RESPONSIBLE investigator;
patients receiving nonprohibited medications or substances known to interact with
CYP450 isoenzymes may be eligible but should be monitored carefully; questions about
eligibility related to concommitant use of medications should be discussed with the
Principal Investigator

- HIV-positive patients receiving combination anti-retroviral therapy are excluded from
the study

- Patients requiring oral anticoagulants (coumadin, warfarin) are eligible provided
there is increased vigilance with respect to monitoring INR. If medically appropriate
and treatment available, the investigator may also consider switching these patients
to 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
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

- 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 nasopharyngeal
cancer

- Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for
nitrosoureas or mitomycin C) prior to entering the study or those who have not
recovered from AEs due to agents administered more than 4 weeks earlier

- Patients may not have received any other investigational agents within 28 days of
study entry

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

- The following lists of medications/substances are moderate to significant
inhibitors/inducers of CYP3A4 that, if administered concomitantly with SB-715992, may
alter 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-715992
through 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 the
first 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 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

- History of allergic reactions attributed to compounds of similar chemical or biologic
composition to SB-715992

- 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

- Pregnant women are excluded from this study because SB-715992 is a mitotic inhibitor
with 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 SB-715992, breastfeeding should be discontinued if the
mother is treated with SB-715992