A Multi-Institution Phase II Study of Pralatrexate With Vitamin B12 and Folic Acid Supplementation for Previously Treated Recurrent or Metastatic Head and Neck Squamous Cell Cancer (HNSCC)

Inclusion Criteria:

- Patients must have histopathologically confirmed recurrent and/or metastatic squamous
cell carcinoma of the head and neck, including unknown primary squamous cell
carcinomas of the neck. Confirmation of biopsy/diagnosis will be performed at MSKCC
or at participating sites (NYU Cancer Institute/NYU Medical Center/ Bellevue Hospital
Center).

- Patients must be at least 18 years of age.

- ECOG performance status must be ≥ 0 or 1.

- Disease must be measurable by RECIST version 1.1 criteria.

- Patients must have been previously treated with systemic chemotherapy (i.e.,
chemotherapy and/or targeted therapies such as cetuximab for recurrent/metastatic
HNSCC,.

- At least four weeks must have elapsed from previous radiation therapy. Patients must
have recovered from the acute toxic effects of treatment prior to study enrollment.

- Patients must have adequate organ function, as follows:

Adequate bone marrow reserve: absolute neutrophil count (ANC) > 1,000 cells/mm3, platelets
> 100,000 cells/mm3, and hemoglobin > 9 g/dL Hepatic: AST and ALT ≤ 3 X upper limit of
normal (ULN); AST and ALT ≤ 5 X ULN if liver metastasis present; Total bilirubin ≤ 1.5 x
ULN unless Gilbert's disease is present Renal: Serum creatinine ≤ 1.5 mg/dL or creatinine
clearance (by either 24 hour urine collection or Cockcroft-Gault equation) > or = to 55
ml/min

- Both women and men and members of all races and ethnic groups are eligible for this
trial.

- Women of childbearing potential must have a negative serum pregnancy test within 14
days of treatment. Both men and women must agree to use a reliable method of birth
control until 30 days following the last dose of study drug.

Exclusion Criteria:

- History of any brain metastases unless resected with no evidence for > 12 weeks and
not on steroids

- Women who are lactating

- Other active malignancy, other than indolent malignancies which the investigator
determines are unlikely to interfere with treatment and safety analysis

- Patients who have undergone an allogeneic stem cell transplant