Inclusion Criteria:

- Previously untreated, histologically proven primary squamous cell carcinoma arising
in the oral cavity, oropharynx, or supraglottic larynx, and amenable to transoral
approach

- Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 (see Appendix C)

- Measurable disease as per RECIST1.1

- Age ≥18 years

- Adequate bone marrow function as demonstrated by: Absolute neutrophil count (ANC) ≥
1,500 cells/mm3; Hgb > 10 g/dL (use of transfusion to reach this threshold prior to
study initiation is acceptable); Platelet count ≥ 100,000/mm3

- Adequate hepatic and renal function as demonstrated by: Aspartate aminotransferase
(AST) and alanine aminotransferase (ALT) ≤ 2.5 x upper limit of normal (ULN); Total
serum bilirubin ≤1.5 mg/dL; Creatinine clearance (CrCL) ≥ 40mL/min as measured via
Cockcroft-Gault

- Left ventricular ejection fraction (LVEF) must be > the lower limit of normal (LLN)
per institutional standards by either echocardiography or radionuclide-based multiple
gated acquisition (MUGA)

- Negative serum β-hCG pregnancy test within 72 hours of day 1 of induction
chemotherapy in women of child-bearing potential

- All males and females of childbearing potential must agree to use adequate
contraception during the study. Adequate contraception is defined as any medically
recommended method (or combination of methods) as per standard of care. Females of
non-childbearing potential are those who are postmenopausal greater than 1 year or
who have had a bilateral tubal ligation or hysterectomy

- Signed an institutional review board (IRB)-approved informed consent document for
this protocol.

Exclusion Criteria:

- T1N0 disease or T2N0 disease

- Any metastatic disease

- Not considered eligible for any of the chemotherapy agents included in the induction
regimen.

- Current active hepatic or biliary disease (with exception of patients with Gilbert's
syndrome, asymptomatic gallstones, liver metastases or stable chronic liver disease
per investigator assessment)

- Major surgery within 3 weeks prior to day 1 of study treatment from which the patient
has not completely recovered

- Current use of a prohibited medication or requires any of these medications during
treatment with lapatinib prior to study entry

- Receiving any investigational agent currently, or within 2 weeks of Day 1 of
treatment on this study

- Active, serious infection, medical, or psychiatric condition that would represent an
inappropriate risk to the patient or would likely compromise achievement of the
primary study objective, including unstable angina, serious uncontrolled cardiac
arrhythmia, uncontrolled infection, or myocardial infarction ≤ 6 months prior to
study entry

- Adequate swallowing function or gastric-tube for drug administration. Of note,
lapatinib can be administered via G-tube in a slurry for patients who cannot swallow

- Other prior or concomitant malignancies with the exception of: Non-melanoma skin
cancer; In-situ malignancy; Low-risk prostate cancer after curative therapy; Other
cancer for which the patient has been disease free for ≥ 3 years

- Pregnant or lactating women, or adults of reproductive potential who do not agree to
use adequate contraception during study treatment (see definition of adequate
contraception