Patient description: The patient is a 60 year old man complaining of frequent headaches, generalized bone pain and difficulty chewing that started 6 years ago and is worsening. Examination shows bilateral swellings around the molars. The swellings have increased since his last examination. Several extraoral lesions are detected in the head and face. The swellings are non-tender and attached to the underlying bone. Further evaluation shows increased uptake of radioactive substance as well as an increase in urinary pyridinoline. His serum alkaline phosphatase is 300 IU/L (the normal range is 44- 147 IU/L). His family history is only significant for hypertension in his mother and DM type 2 in his father. The diagnosis of Paget's Disease of Bone was confirmed and Bisphosphonate will be started as first-line therapy.

Clinical trial eligibility criteria: eligible ages (years): 18.0-999.0,  Carcinoma, Squamous Cell of Head and Neck Squamous Cell Carcinoma of the Head and Neck Squamous Cell Carcinoma, Head And Neck Each patient must meet all of the following to be enrolled in the study Patients must have histologically confirmed HNSCC, from any primary site. Nasopharyngeal carcinoma, WHO Type I (keratinizing), will be included. Squamous cell carcinoma of unknown primary, clearly related to the head and neck, will be included Recurrent/metastatic disease, fulfilling at least one of the defined below Incurable disease as assessed by surgical or radiation oncology Metastatic (M1) disease Persistent or progressive disease following curative-intent radiation, and not a candidate for surgical salvage due to incurability or morbidity. Patients who decline radical surgery are eligible In the dose-finding phase, patients may be cetuximab-exposed or cetuximab-naïve. If the most recent line of therapy included cetuximab, a two-week washout period without cetuximab dosing is required Patients must have previously received, not tolerated, or been judged clinically unsuitable for platinum-containing therapy In the dose-expansion phase, patients must be cetuximab-resistant by fulfilling at least one of the defined below Disease recurrence within 6 months of completing definitive radiotherapy for locally advanced disease. Radiation must have included concurrent cetuximab. Induction chemotherapy, if given, may or may not have included cetuximab  Patients meeting any of the following are not to be enrolled in the study Nasopharyngeal primary site, if WHO Type II or III (non-keratinizing) History of severe allergic or anaphylactic reactions or hypersensitivity to recombinant proteins or excipients in the investigational agent Prior treatment with an HGF/cMet inhibitor such as rilotumumab, crizotinib, MetMAb, or ARQ197 Uncontrolled central nervous system (CNS) metastases, including leptomeningeal metastases, are not allowed. Subjects with previously treated brain metastases will be allowed if the brain metastases have been stable without steroid treatment for at least 4 weeks following prior treatment (radiotherapy or surgery) Failure to recover to Grade 1 or baseline from all toxic effects of previous chemotherapy, radiation therapy, biologic therapy, and/or experimental therapy, with the exception of: alopecia, Grade ≤ 2 peripheral neuropathy, Grade ≤ 2 cetuximab-related rash or other skin changes, hypomagnesemia (acceptable values detailed below), hypokalemia (acceptable values detailed below), and the acceptable hematologic values summarized above. A washout period of 2 weeks from prior cetuximab is required; a washout period of 3 weeks from any prior cytotoxic chemotherapy or investigational drug is required Significant pulmonary disease, including pulmonary hypertension or interstitial pneumonitis Decreased serum albumin < 30 g/L (< 3 g/dL) Peripheral edema ≥ Grade 2 per NCI-CTCAE version 4.0