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