• Patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC)

• Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or 2 (Appendix C)

• Age 18 years or above.

• Laboratory values:

• WBC ≥2000/uL

• Hgb \>8.0 g/dl (patients may be transfused to reach this level)

• Platelets \>75,000 cells/mm3

• Serum creatinine clearance ≥ 50 mL/min measured or calculated by Cockcroft-Gault (C-G) equation

• Negative bHCG (urine/serum) Women of childbearing potential only

• AST (SGOT) and ALT (SGPT) ≤2.5 × upper limit of laboratory normal (ULN) OR ≤ 5 × ULN for participants with liver metastases

• Alkaline phosphatase ≤2.5 × ULN OR ≤ 5 × ULN for participants with liver metastases

• Total bilirubin ≤1.5 × ULN. If total bilirubin is \>1.5, conjugated bilirubin must be ≤ ULN (conjugated bilirubin only needs to be tested if total bilirubin exceeds ULN). If there is no institutional ULN, then conjugated bilirubin must be \< 40% of total bilirubin.

• Patients positive for hepatitis B core antibody (anti-HBc, total), are eligible only if HBV DNA is non-detectable by qPCR.

• Patients positive for hepatitis C virus (HCV) antibody are eligible only if HCV RNA is non-detectable by qPCR.

• Patients positive for HIV 1/2 antibodies, are eligible if ARV treatment compliant with documented stable CD4 \> 300 for at least 6 months and undetectable viral load

• Ability to give informed consent and comply with the protocol.

• Anticipated lifespan greater than 12 weeks.

• Women of childbearing potential must have negative serum/urine pregnancy test \<5 days prior to start of study.

• Males and women of childbearing potential, must agree to take appropriate precautions to avoid pregnancy during treatment and through 180 days after last dose of study treatment (see Appendix A).