Inclusion Criteria:

- Department of Pathology at MSKCC confirmation of diagnosis of oropharynx squamous
cell cancer, stage IVA/IVB, that is HPV associated.

Evidence of HPV can be p16 immunohistochemistry and/or HPV in situ hybridization positive
test result on tumor tissue, either at MSKCC or other CLIA-approved lab.

- Age ≥ 18 years of age

- Karnofsky Performance Status ≥ 80

- Adequate organ function, as follows:

Adequate bone marrow reserve: absolute neutrophil count (ANC) ≥ 1.5 X 109/L, platelets ≥
160 X 109/L, hemoglobin ≥ 12 g/dL Hepatic: total bilirubin within normal limits (≤ 1.0
mg/dL); alkaline phosphatase (AP), aspartate transaminase (AST) and alanine transaminase
(ALT) ≤ 1.5 X ULN (upper limit of normal) Renal: Serum creatinine ≤ 1.3 mg/dL. Patients
with serum creatinine > 1.3 mg/dL may be eligible if creatinine clearance (CrCl) ≥ 55
mL/min based on the standard Cockroft and Gault formula.

- Patients of childbearing potential must have a negative serum pregnancy test within
14 days of treatment. Patients must agree to use a reliable method of birth control
during and for 6 months following the last dose of study drug.

- Ability to swallow oral medication.

- Expansion Cohort only: At least one unstained slide from pre-treatment diagnostic
biopsy or fine needle aspirate must be available for correlative immunohistochemistry
study.

Exclusion Criteria:

- Prior chemotherapy or radiation for tonsillar or base of tongue squamous cell cancer

- History of hemolytic anemia or thalassemia

- Active infection or serious underlying medical condition that would impair the
patient's ability to receive protocol treatment.

- Current therapeutic anticoagulation with Coumadin (warfarin)

- Current or prior treatment with ribavirin

- Known active Hepatitis B or C

- Any prior documented history of transient ischemic attack (TIA) or cerebrovascular
accident (CVA)

- New York Heart Association (NYHA) Grade II or greater congestive heart failure

- Clinically significant peripheral vascular disease

- Inability to discontinue any of the following potent P-gp inhibitors (cyclosporine,
erythromycin, ketoconazole, itraconazole, quinidine, phenobarbital salt with
quinidine, ritonavir, valspodar, verapamil) or inducers (St John's wort, rifampicin).

- Known pre-existing interstitial lung disease.

- Presence of poorly controlled gastrointestinal disorders that could affect the
absorption of the trial drug (e.g. Crohn's disease, ulcerative colitis,
malabsorption, or CTC grade ≥2 diarrhea of any etiology) based on treating physician
assessment.