Potentiation of Cetuximab by Tregs Depletion With CSA in Advanced Head & Neck Cancer

In this study, patients with head and neck squamous cell carcinoma (HNSCC) will be given
low-dose cyclophosphamide in combination with standard of care cetuximab. Tumor biopsies will
be collected before and six weeks after treatment for measurement of tumor infiltration by
effector cells, including CD8+ T cells, natural killer (NK) cells, and monocytes. In
addition, the proportion of Tregs to effector cells will be measured in peripheral blood at
the same time points.

Inclusion Criteria:

- Histologically documented squamous cell carcinoma of the head and neck (irrespective
of site of primary - nasopharyngeal, oral cavity, oropharyngeal, laryngeal or unknown
primary) that is metastatic/incurable and has progressed on a first line chemotherapy
regimen.

- Progression of measurable disease within the last 6 weeks based on Response Evaluation
Criteria in Solid Tumors (RECIST) criteria

- If the patient has received prior treatment with anti-epidermal growth factor receptor
(EGFR) therapy as a part of definitive therapy concurrent with radiation, the time
from the last cetuximab exposure must be > 180 days.

- Must be at least 30 days from prior treatment and have recovered from the reversible
effects of previous anti-cancer treatment

- Age ≥ 18 years

- Eastern Cooperative Oncology Group (ECOG) Performance Status 0, 1 or 2

- Adequate bone marrow, renal and hepatic function within 14 days of study enrollment
defined as:

- Bone marrow: White blood cells (WBC) > 3,000/uL; absolute neutrophil count >
1,500/uL; platelets > 100,000/uL

- Renal: creatinine ≤ 2.5 times the institutional upper limit of normal (ULN)

- Hepatic: total bilirubin < 1.5 X institutional ULN; aspartate
aminotransferase/alanine aminotransferase (AST[SGOT] and ALT[SGPT]) < 2.5 X
institutional ULN

- Albumin > 3.0 gm/dL

- Women of childbearing potential and fertile men must be willing to use an acceptable
method of birth control (i.e., a hormonal contraceptive, intra-uterine device,
diaphragm with spermicide, condom with spermicide, or abstinence) for the duration of
the study and for 60 days after the last dose of study drug.

- Voluntary written consent before performance of any study-related procedure not part
of normal medical care, with the understanding that consent may be withdrawn by the
patient at any time without prejudice to future medical care

Exclusion Criteria:

- Pregnant or lactating - females of child bearing potential must have a negative
pregnancy test within 14 days of study enrollment as cyclophosphamide is Pregnancy
Category D

- History of another active primary invasive cancer within the previous 2 years,
excluding non-melanoma skin cancer

- The patient is receiving concurrent treatment with other anticancer therapy, including
chemotherapy, immunotherapy, hormonal therapy, radiotherapy (RT), chemoembolization,
or targeted therapy. Patients receiving palliative radiation therapy to bony
metastases prior to the first dose of study medication are eligible.

- Chronic steroid dependence

- Known HIV-positive patients and those with other acquired/inherited immunodeficiency
hepatitis B, hepatitis C, connective tissue disease, or other clinical diagnosis,
ongoing or intercurrent illness that in the Investigator's opinion should preclude the
subject from participation

- History of gastrointestinal disease causing malabsorption or obstruction such as, but
not limited to Crohn's disease, celiac sprue, tropical sprue, bacterial
overgrowth/blind loop syndrome, gastric bypass surgery, strictures, adhesions,
achalasia, bowel obstruction, or extensive small bowel resection

- Inability to take medications by mouth

- History of allergic reactions attributed to compounds of similar chemical or biologic
composition

- Active autoimmune disease, chronic inflammatory condition, conditions requiring
concurrent use of any systemic immunosuppressants or steroids. Mild-intermittent
asthma requiring only occasional beta-agonist inhaler use or mild localized eczema
will not be excluded.

- Previous allo-transplant of any kind