Durvalumab With or Without Metformin in Treating Participants With Head and Neck Squamous Cell Carcinoma

Inclusion Criteria:

* Pathologically confirmed head and neck squamous cell carcinoma (HNSCC), with measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
* Any stage HNSCC of the 1) oral cavity, 2) oropharynx, 3) larynx, 4) hypopharynx, 5) nasal cavity/paranasal sinuses, 6) unknown primary, 7) skin considered to have resectable disease. Patients with recurrent disease that is amenable to surgery are eligible
* Performance status 0-1
* Must have a life expectancy of at least 12 weeks as judged by the treating physician
* Body weight \>30 kg
* Absolute neutrophil count 1500/ul or more
* Platelets 100,000/ul or more
* Hemoglobin 9 g/dl or more
* Bilirubin less than or equal to 1.5 x the upper limit of normal (except subjects with Gilbert syndrome, who can have total bilirubin \<3 mg/dl)
* Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) less than or equal to 2.5 x the upper limit of normal
* Glomerular filtration rate (GFR) greater than or equal to 40 ml/min using the Cockcroft-Gault formula or measured creatinine clearance using 24 hours urine collection
* Women of reproductive potential should have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin \[HCG\]), which must also be confirmed as negative within 28 days of the start of study drugs
* Women of reproductive potential must use highly effective contraception methods to avoid pregnancy for 90 days after the last dose of study drugs. "Women of reproductive potential" is defined as any female who has experienced menarche and who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy) or who is not postmenopausal. Menopause is defined clinically as 12 months of amenorrhea in a woman over 45 in the absence of other biological or physiological causes. In addition, women under the age of 55 must have a documented serum follicle stimulating hormone (FSH) level less than 40 mIU/mL
* Men of reproductive potential who are sexually active with women of reproductive potential must use any contraceptive method with a failure rate of less than 1% per year. Men who are receiving the study medications will be instructed to adhere to contraception for 90 days after the last dose of study drugs. Men who are azoospermic do not require contraception
* Informed consent: All subjects must be able to comprehend and sign a written informed consent document

Exclusion Criteria:

* Patients with nasopharyngeal carcinoma or salivary gland primaries
* Any history of a sever hypersensitivity reaction to any monoclonal antibody
* Any history of allergy to the study drug components
* Any prior history of exposure to an anti PD-L1including durvalumab or PD1-directed therapy
* Patients who are already taking metformin, or who have taken metformin in the preceding 4 weeks
* Diabetic patients who are managed by taking metformin or insulin
* Major surgical procedure (as defined by the investigator) within 28 days prior to the first dose of durvalumab

  \* Note: Local surgery of isolated lesions for palliative intent and biopsy procedures are acceptable
* Subjects who are on medication that are contraindicated with metformin under current Food and Drug Administration (FDA) recommendations; current recommendations reflect caution when metformin is used with insulin, sulfonylureas, and iodinated contrast dye
* Subjects who have received iodinated contrast dye less than 12 hours prior to screening meet a temporary exclusion criterion to receive metformin. These patients cannot start investigational metformin until 12 hours have elapsed from contrast administration. Subjects who are scheduled for iodinated contrast dye are not excluded but will be asked to hold their doses prior to dye administration
* Mean QT interval corrected for heart rate (QTc) greater than or equal to 470 ms calculated from 3 electrocardiograms (EKGs) using Fridericia's Correction
* Any concurrent malignancies; exceptions include- basal cell carcinoma of the skin, squamous cell carcinoma of the skin of a secondary location, superficial bladder cancer or in situ cervical cancer that has undergone potentially curative therapy. Patients with a history of other prior malignancy must have been treated with curative intent and must have remained disease-free for 2 years post-diagnosis
* Any unresolved toxicity National Cancer Institute NCI Common Terminology Criteria for Adverse Events (CTCAE) version (v) 5.0 grade \>= 2 from previous anticancer therapy with the exception of alopecia, vitiligo, and the laboratory values defined in the inclusion criteria. Patients with grade \>= 2 neuropathy will be evaluated on a case-by-case basis after consultation with the Study Physician. Patients with irreversible toxicity not reasonably expected to be exacerbated by treatment with durvalumab may be included only after consultation with the study physician
* Any diagnosis of immunodeficiency or receiving systemic steroid therapy with a dose of \>10 mg prednisone per day or equivalent or any other form of immunosuppressive therapy within 14 days of initiation of therapy, or a prior history of allogenic organ transplantation
* Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease \[e.g., colitis or Crohn's disease\], diverticulitis \[with the exception of diverticulosis\], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome \[granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc\]). The following are exceptions to this criterion:

  * Patients with vitiligo or alopecia
  * Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement
  * Any chronic skin condition that does not require systemic therapy
  * Patients without active disease in the last 5 years may be included but only after consultation with the study physician
  * Patients with celiac disease controlled by diet alone
* Patients must not be receiving any other investigational agents
* Receipt of a live attenuated vaccine within 30 days prior to the first dose of drug on trial
* Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, interstitial lung disease, serious chronic gastrointestinal conditions associated with diarrhea, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring adverse events (AEs) or compromise the ability of the patient to give written informed consent
* Patients must not be pregnant or breastfeeding
* Active infection including tuberculosis (clinical evaluation that includes clinical history, physical examination and radiographic findings, and tuberculosis \[TB\] testing in line with local practice), hepatitis B virus (HBV) (known positive HBV surface antigen \[HBsAg\] result), hepatitis C, or human immunodeficiency virus (positive HIV 1/2 antibodies). Patients with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody \[anti-HBc\] and absence of HBsAg) are eligible. Patients positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA