Cetuximab With or Without Tivantinib in Treating Patients With Head and Neck Cancer That Is Recurrent, Metastatic, or Cannot Be Removed By Surgery

Inclusion Criteria:

• Histologically/cytologically confirmed diagnosis of squamous cell carcinoma of head and neck origin not amenable to curative intent therapy; both human papillomavirus (HPV) positive (+) and HPV negative (-) are eligible, but status has to be known prior to randomization; any type of tissue based HPV assessment is acceptable (e.g. p16 immunohistochemistry [IHC] or in situ hybridization [ISH]); if local HPV testing is not available slides can be sent to the University of Chicago for HPV testing using p16 IHC or comparable
• Presence of measurable lesions (Response Evaluation Criteria in Solid Tumors [RECIST])
• Availability of tissue (>= 17 tumor containing formalin-fixed, paraffin-embedded [FFPE] slides/sections)
• Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1
• Patients who have received cetuximab or another inhibitor of epidermal growth factor receptor (EGFR) in the curative intent treatment setting (e.g. with radiation or during induction chemotherapy [prior to definitive, curative intent therapy]) are eligible for the study
• Life expectancy of greater than 8 weeks
• Hemoglobin >= 9.0 g/dL
• Leukocytes >= 3,000/mcL
• Absolute neutrophil count >= 1,500/mcL
• Platelets >=100,000/mcL
• Total bilirubin =< 1.5 X institutional upper limit of normal
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SGPT]) =< 2.5 X institutional upper limit of normal
• Serum creatinine =< 1.5 X institutional upper limit of normal OR creatinine clearance >= 60 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal
• Presence of measurable lesions by RECIST: patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as >= 20 mm with conventional techniques or as >= 10 mm with spiral computed tomography (CT) scan
• Human immunodeficiency virus (HIV)-positive patients with normal immune function (cluster of differentiation [CD]4 count > 200) are eligible if there are no drug interactions with ARQ 197 (tivantinib) or cetuximab
• 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 she or her partner is participating in this study, she should inform her treating physician immediately; men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of ARQ 197 (tivantinib) administration
• Ability to understand and the willingness to sign a written informed consent document
• Patients must be able to swallow ARQ 197 (tivantinib) by mouth, unless adequate data about administration by gastronomy tube (G-tube) becomes available

Exclusion Criteria:

• Patients who have ad chemotherapy or radiotherapy within 2 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 2 weeks earlier
• Patients with tumors that progress within 3 months of definitive treatment (typically chemoradiation or radiation) are ineligible
• Patients who have received more than 2 prior cytotoxic treatments in the palliative treatment setting are ineligible
• Patients who have received treatment with an EGFR or MET inhibitor in the palliative treatment setting are ineligible
• Patients with known, active brain metastases should be excluded from this clinical trial; patients with treated brain metastases stable for >= 12 weeks are eligible; use of corticosteroids is acceptable on a low maintenance or tapering dose schedule
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to ARQ 197 (tivantinib) or cetuximab
• Concurrent life-threatening diseases: patients with diseases which with reasonable certainty do not limit life expectancy to 12 months or less are eligible; assessment of such concurrent illnesses should be by the principal investigator
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated with ARQ 197 (tivantinib)
• Concurrent use of warfarin (therapeutic use) is allowed, but requires close monitoring of prothrombin time (PT)/international normalized ratio (INR)
• ARQ 197 (tivantinib) is metabolized by cytochrome P450 2C19 (CYP2C19), and to a lesser extent cytochrome P450 3A4 (CYP3A4); the metabolism and consequently overall pharmacokinetics of ARQ 197 (tivantinib) could be altered by inhibitors and/or inducers or other substrates of CYP2C19 and CYP3A4; while inhibitors/inducers of these cytochrome P450 isoenzymes are not specifically excluded, investigators should be aware that ARQ 197 (tivantinib) exposure may be altered by the concomitant administration of these drugs
• History of congestive heart failure defined as class II to IV per New York Heart Association (NYHA) classification; clinically significant bradycardia or other uncontrolled, cardiac arrhythmia defined as >= grade 3 according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 4.0, or uncontrolled hypertension; myocardial infarction occurring within 6 months prior to study entry (myocardial infarction occurring > 6 months prior to study entry is permitted)
• Patients may not be receiving any other investigational agents