Phase I/II Study OF Metformin in Combination With Cisplatin and Radiation in Head and Neck Squamous Cell Carcinoma

INCLUSION CRITERIA

• Diagnosis: Patients must have histologically or cytologically confirmed squamous cell carcinoma (SCC) of the oral cavity, oropharynx, hypopharynx or larynx. Patients eligible for inclusion must have stage III-IV SCC of the above sites based on current AJCC clinical and imaging based staging (see Appendix A for staging criteria). For the phase II component, patients should present with: 1) HPV- SCC or 2) HPV+ SCC and a concomitant ≥10pack-year smoking history documented in the clinical record; HPV status will be ascertained using the currently utilized clinical standard of p16 overexpression via immunohistochemistry for all patients. Immunohistochemistry to determine p16 overexpression is only a requirement for oropharyngeal disease.
• Disease Status: Only patients with active, measurable disease will be included in the study.
• Prior Therapy: Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study. Patients treated with chemotherapy (i.e. cisplatin) and/or EBRT for a cancer at a different, non-head and neck site, will be eligible for the trial. Patients previously treated with chemotherapy and/or EBRT for a cancer of the head and neck region, irrespective of histology will not be eligible to participate in the trial.
• Myelosuppressive chemotherapy: Must not have received within 4 weeks of enrollment onto this study (6 weeks if prior nitrosourea).
• Hematopoietic growth factors: At least 7 days since the completion of therapy with a growth factor.
• Biologic (anti-neoplastic agent): At least 7 days since the completion of therapy with a biologic agent.
• Monoclonal Antibody: At least 6 weeks must have elapsed since prior therapy that includes a monoclonal antibody.

Other: For agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur.

• XRT: >/= 14days for local palliative XRT (small port); >/= 90days must have elapsed if prior TBI, craniospinal XRT or if >/= 50% radiation of pelvis; >/= 45days must have elapsed if other substantial bone marrow radiation.
• Stem Cell Transplant or Rescue: No evidence of active graft vs. host disease and >/= 2 months must have elapsed since transplant.
• Age: Patients must be >/=18 years of age. Because no dosing or adverse event data are currently available on the use of metformin in cancer patients /= 3,000/mcL
• absolute neutrophil count >/= 1,500/mcL
• platelets >/= 100,000/mcL
• total bilirubin within normal institutional limits
• AST(SGOT) /= 60 mL/min/1.73 m2 for patients with creatinine levels > institutional normal
• Patients must be candidates for standard of care treatment consisting of chemotherapy (cisplatin) and radiation.
• Willingness to Use Contraception: The effects of metformin on the developing human fetus at the recommended therapeutic dose are unknown. For this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
• Informed Consent: Ability to understand and the willingness to sign a written informed consent document.

EXCLUSION CRITERIA

• Concomitant Medications: Patients may not be receiving any other investigational agents.
• Brain metastases: Patients with known brain metastases will be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.
• Prior Allergies: History of allergic reactions attributed to compounds of similar chemical or biologic composition to me