Potentiation of Cetuximab by Tregs Depletion With CSA in Advanced Head & Neck Cancer
Condition: Head and Neck Cancer; Head and Neck Squamous Cell Carcinoma
MeSH terms: Head and Neck Neoplasms; Squamous Cell Carcinoma of Head and Neck
Intervention: Cyclophosphamide; Cetuximab
Intervention description: Patients will be given oral cyclophosphamide 50 mg twice daily to be self-administered starting the first day of therapy with weekly cetuximab for 12 weeks or until disease progression.; The initial dose of cetuximab 400 mg/m^2 is administered over 120 minutes followed by weekly infusions of cetuximab 250 mg/m^2 intravenously (IV) over 60 minutes.
Intervention MeSH terms: Cyclophosphamide; Cetuximab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 7.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: head and neck cancer; metastatic squamous cell cancer

Summary:

      This is a feasibility study to assess the effectiveness of cetuximab when administered with
      low dose oral cyclophosphamide. Patients with metastatic squamous cell cancer of head and
      neck who have progressed on first line chemotherapy other than a cetuximab containing regimen
      will be treated with standard of care weekly cetuximab and twice daily low dose oral
      cyclophosphamide for 12 weeks.
    

Eligibility criteria:

        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