Capecitabine and Lapatinib Ditosylate in Treating Patients With Squamous Cell Cancer of the Head and Neck

PRIMARY OBJECTIVE:

I. Overall survival (OS) will be the primary endpoint.

SECONDARY OBJECTIVES:

I. Progression free survival (PFS). II. Time to disease progression and sites of progression.
III. Response rate. IV. Toxicity of the combination in this population. V. Quality of life.

OUTLINE:

Patients receive oral lapatinib ditosylate once daily on days 1-21 and oral capecitabine
twice daily on days 1-14. Courses repeat every 21 days in the absence of disease progression
or unacceptable toxicity. After completion of study treatment, patients are followed every 3
months for up to 5 years.

Inclusion

- Histologically or cytologically confirmed SCCHN

- All primary sites are eligible excluding nasopharyngeal

- Metastatic disease or locally recurrent disease not felt amenable to curative therapy
(as determined by a physician)

- ECOG performance status 0-2

- No prior chemotherapy in the metastatic / locally advanced, recurrent incurable
setting; patients may have received prior curative-intention chemotherapy including
induction chemotherapy, chemotherapy concurrent with radiation and adjuvant
chemotherapy

- No prior capecitabine; patients who have received 5-FU or other fluoropyrimidines in
the curative-intention setting will not be excluded, as long as more than 6 mos have
elapsed since prior 5-FU exposure

- No previous history of Lapatinib

- Previous use of cetuximab in the curative-intention setting will not result in
exclusion, as long as at least four weeks have elapsed since prior C225 exposure

- Patients may have received radiation therapy in the definitive, adjuvant or metastatic
setting; radiation therapy must be completed at least 14 days prior to study
participation

- ECOG performance status of 0-2 (Karnofsky >= 60%)

- Must have normal organ and marrow function

- Laboratory tests should be completed within 14 days prior to registration

- Left ventricular ejection fraction (LVEF) can be determined by either echocardiography
or nuclear scintigraphy and should be obtained within 21 days of enrollment

- Platelets >= 100,000/mm^3

- Total bilirubin =< 2

- Albumin > 2.5

- AST(SGOT)/ALT(SGPT) =< 5.0 X institutional upper limit of normal (for patients with
hepatic metastases) =< 3.0 X institutional upper limit of normal (for patients without
hepatic metastases)

- GFR > 30 (by standard Cockroft and Gault formula)

- LVEF >= 50%

- Patients may receive anticoagulant medication while on study

- Patients may not receive other antineoplastic therapies such as chemotherapy or
radiation treatments while on study; patients may not receive other experimental
treatments while on study; patients requiring radiation treatments during
protocol-based treatment will be taken off study

- Patients may receive concurrent bisphosphonate therapy as well as hormonal
manipulations for appetite while on study

- Patients must neither be pregnant nor expect to become pregnant while on study

- Patients must have the ability to understand and the willingness to sign a written
informed consent document

- Adequate swallowing function or gastric-tube for drug administration

- No disability with absorption of internal medications

- Adequate nutritional status: Patients will not be excluded based on previous weight
loss but will be required to have adequate nutrition at the time of study entry as
measured by serum albumin

- ANC >= 1,500/mm^3

- Women of child-bearing potential and men must agree to use adequate contraception
prior to study entry and for the duration of study participation

Exclusion

- Patients who have received prior capecitabine chemotherapy or lapatinib

- Patients with brain metastases may participate if they have undergone appropriate
treatment for the lesion(s), are at least two weeks post treatment without evidence
for post-treatment progression, have no significant neurologic symptoms, and are no
longer on steroids for brain metastases

- Patients with symptoms concerning for CNS metastases should be evaluated with imaging
prior to study participation

- Less than 3 weeks elapsed since prior exposure to chemotherapy

- LVEF < 50% or symptomatic congestive heart failure (CHF)

- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection requiring IV antibiotics, 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 due to the potential for teratogenic or abortifacient
effects of capecitabine and lapatinib; because there is a potential risk for adverse
events in nursing infants secondary to treatment of the mother with these agents,
breastfeeding should be discontinued prior to participation of the mother on study

- Other active, invasive malignancy requiring ongoing therapy or expected to require
systemic therapy within two years; localized squamous cell carcinoma of the skin,
basal-cell carcinoma of the skin, carcinoma in-situ of the cervix, or other
malignancies requiring locally ablative therapy only will not result in exclusion

- Have received treatment within the last 30 days prior to study entry with any drug
that has not received regulatory approval for an indication at the time of study entry

- Previous CHF or other cardiac conditions shall not result in exclusion if the treating
physician does not see contraindication to these medications; if contraindication is
controversial, cardiac consultation will be obtained prior to the initiation of
therapy

- Anti-cancer therapy (other than the investigational regimen) is prohibited from 3
weeks before the first dose of investigational product through discontinuation unless
otherwise noted

- Investigational drugs are not permitted from 3 weeks (21 days) or 5 half-lives,
whichever is longer, prior to the first dose and up through 30 days after the last
dose of investigational product

- CYP3A4 inducers and inhibitors, antacids, and herbal or dietary supplements

- Concurrent radiation therapy and surgery for SCCHN is prohibited during therapy