Cetuximab With or Without Tivantinib in Treating Patients With Head and Neck Cancer That Is Recurrent, Metastatic, or Cannot Be Removed by Surgery
Condition: Head and Neck Squamous Cell Carcinoma; Recurrent Head and Neck Carcinoma
MeSH terms: Carcinoma; Head and Neck Neoplasms; Squamous Cell Carcinoma of Head and Neck; Recurrence
Intervention: Cetuximab; Laboratory Biomarker Analysis; Tivantinib
Intervention description: Given IV; Correlative studies; Given PO
Intervention MeSH terms: Cetuximab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 81.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This randomized phase II trial studies how well cetuximab with or without tivantinib works in
      treating patients with head and neck cancer that has come back (recurrent), has spread to
      other places in the body (metastatic), or cannot be removed by surgery. Monoclonal
      antibodies, such as cetuximab, may interfere with the ability of tumor cells to grow and
      spread. Tivantinib may stop the growth of tumor cells by blocking some of the enzymes needed
      for cell growth. It is not yet known whether cetuximab is more effective with or without
      tivantinib in treating patients with head and neck cancer.
    

Eligibility criteria:

        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 (although not required for consenting); any type of tissue based HPV
             assessment is acceptable (e.g. p16 immunohistochemistry [IHC] or HPV in situ
             hybridization [ISH]); if local HPV testing is not available slides can be sent to the
             University of Chicago for HPV testing; please note that p16 IHC is generally only
             considered to be accurate for oropharyngeal tumors

          -  Presence of measurable lesions (as per Response Evaluation Criteria in Solid Tumors
             [RECIST] 1.1); generally a >= 10 mm tumor lesion (in the longest diameter by computed
             tomography [CT] scan) or a lymph node >= 15 mm (short axis) is considered measurable
             disease when evaluated by CT scan (with a slice thickness no greater than 5 mm)

          -  Availability of tissue (10 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 glutamate pyruvate 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

          -  Patients must be able to swallow ARQ 197 (tivantinib) by mouth, unless adequate data
             about administration by gastrostomy (G)-tube becomes available; tablets may be
             crushed, but must be taken orally

          -  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

        Exclusion Criteria:

          -  Patients who have had 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

          -  Nasopharyngeal tumors that show lymphoepithelioma histology

          -  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 corticosteroid (for patients with brain metastasis and other indications for
             corticosteroid use) 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)

          -  History of congestive heart failure defined as class II to IV per New York Heart
             Association (NYHA) classification; active coronary artery disease (CAD), 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