Ficlatuzumab, Cisplatin and IMRT in Locally Advanced Head and Neck Squamous Cell Carcinoma

Inclusion Criteria: Each patient must meet all of the following inclusion criteria to be enrolled in the study: * Patients must have histologically confirmed squamous cell carcinoma, undifferentiated carcinoma, or poorly differentiated carcinoma of the oral cavity, oropharynx, larynx, or hypopharynx with no evidence of distant metastasis. Biopsy sampling of primary tumor with pathology report documentation of confirmed diagnostic tissue type is required. Patients should be evaluated by a Radiation Oncologist, Medical Oncologist and Otolaryngologist prior to enrolling on study. * Patients must have high risk or intermediate risk disease, defined below. Staging evaluation should be determined by imaging studies and complete head and neck exam in accordance with the American Joint committee on Cancer Staging Manual, 7th edition o High risk patients must meet one of the following criteria: * Unresectable oral cavity * Larynx: T4 any N; T2-3 and ≥N2a * Hypopharynx and p16(-) oropharynx: Stage III-IVb except T1N1 * p16(-) Oropharnyx: Stage III-IVb except T1N1 o Intermediate risk, p16(+) oropharynx patients must meet one of the following criteria: * T3 or ≥ N2a AND ≥10 pack-years tobacco exposure (See Tobacco Assessment Form, Appendix A) * T4 disease, irrespective of smoking status * N3 disease, irrespective of smoking status Note: for oropharyngeal patients, p16 status must be known, and can be performed at the local site. p16-positive disease is defined as ≥70% of tumor cells demonstrating diffuse nuclear and cytoplasmic staining by p16 immunohistochemistry (IHC). A positive test for HPV-16 by in-situ hybridization (ISH), if this is the local site preference for assessing HPV status, may substitute for p16 IHC testing. p16 staining is not required for non-oropharyngeal sites. * Patients must be untreated with curative-intent surgery for current diagnosis of Stage III, IVa, or IVb disease. Diagnostic biopsy of primary tumor and/or nodal sites is permitted. * Diagnostic simple tonsillectomy is permitted, provided patient has RECIST-measurable nodal disease. * Patients with a second HNSCC primary tumor are eligible for this study, provided more than 2 years have elapsed since the first diagnosis of HNSCC, the original tumor was managed with surgery only (no adjuvant chemotherapy or radiotherapy), and has not recurred. * Patients with simultaneous primaries or bilateral tumors are excluded, with the exception of patients with bilateral tonsil cancers or patients with T1-2, N0, M0 resected differentiated thyroid carcinoma, who are eligible. * No prior systemic (chemotherapy or biologic/molecular targeted therapy) or radiation treatment for head and neck cancer. * Patients may have received chemotherapy or radiation for a previous, curatively treated non-HNSCC malignancy, provided at least 2 years have elapsed. * Patients must be untreated with radiation above the clavicles. * Patients with a history of curatively-treated non-HNSCC malignancy must be disease-free for at least 2 years except for excised and cured: carcinoma-in-situ of breast or cervix; non-melanomatous skin cancer; T1-2, N0, M0 resected differentiated thyroid carcinoma; superficial bladder cancer; T1a or T1b prostate cancer comprising \< 5% of resected tissue with normal prostate specific antigen (PSA) since resection. * Diagnostic primary tumor tissue must be available for biomarker correlatives, in both the dose-finding and expansion cohorts. * Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1 (See Appendix B) * Age ≥ 18 * Patients must have measurable disease according to RECIST 1.1 (See Section 6.1) * Patients must have the following laboratory values measured within 28 days of registration: * Absolute neutrophil count (ANC) \> 1500/mm3 * Hemoglobin (Hb) \> 8.0 g/dL * Platelet count (PLT) \> 100,000/mm3 * Creatinine clearance ≥ 45 ml/min determined by 24-hour collection or estimated by the Cockraft-Gault formula: * Calculated Creatinine Clearance = \[(140-age) X (actual body weight in kg) X (0.85 if female)\]/(72 X serum creatinine) * Serum bilirubin \< 2 mg/dL * AST (aspartate aminotransferase) and ALT (alanine aminotransferase) \< 3 times upper limit of normal (ULN) * No prior severe infusion reaction to a monoclonal antibody * Written informed consent must be obtained from all patients prior to beginning therapy. Patients should have the ability to understand and the willingness to sign a written informed consent document. * If a woman of childbearing potential, documentation of negative pregnancy within 14 days prior to first dose. Sexually active patients must agree to use adequate contraceptive measures, while on study and for 30 days after the last dose of study drug. All fertile female subjects (and their partners) must agree to use a highly effective method of contraception. Effective birth control includes (a) intrauterine device (IUD) plus one barrier method; or (b) 2 barrier methods. Effective barrier methods are male or female condoms, diaphragms, and spermicides (creams or gels that contain a chemical to kill sperm). Should a woman become pregnant or suspect she is pregnant while in this study, she should inform her treating physician immediately. Exclusion Criteria: Patients meeting any of the following exclusion criteria are not to be enrolled in the study: * History of severe allergic or anaphylactic reactions or hypersensitivity to recombinant proteins or excipients in the investigational agent. * Distant metastatic disease including CNS or leptomeningeal metastases is not allowed. * Left ventricular ejection fraction (LVEF) ≤ 50%. * 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. * Significant electrolyte imbalance prior to enrollment: * Hypomagnesemia \< 1.2 mg/dL or 0.5 mmol/L. * Hypocalcemia \< 8.0 mg/dL or 2.0 mmol/L. * Hypokalemia \< 3.0 mmol/L. * Significant dermatological disease including but not limited to, skin drying and fissuring, paronychial inflammation, infectious sequelae (eg. blepharitis, cheilitis, cellulitis, cyst). * Peripheral neuropathy ≥ Grade 2 * Significant cardiovascular disease, including: * Cardiac failure New York Heart Association (NYHA) class III or IV. * Myocardial infarction, severe or unstable angina within 6 months prior to Study Day 1. * History of serious arrhythmia (i.e., ventricular tachycardia, or ventricular fibrillation). * Cardiac arrhythmias requiring anti-arrhythmic medications. * Significant thrombotic or embolic events within 3 months prior to Study Day 1. Significant thrombotic or embolic events include but are not limited to stroke or transient ischemic attack (TIA). Catheter-related thrombosis is not a cause for exclusion. Diagnosis of deep vein thrombosis or pulmonary embolism is allowed if it occurred \> 3 months prior to Study Day 1 and the patient has completed or is on stable anti-coagulation therapy. * Any other medical condition (eg, alcohol abuse) or psychiatric condition that, in the opinion of the Investigator, might interfere with the subject's participation in the trial or interfere with the interpretation of trial results. * History of second malignancy within 2 years prior to Study Day 1 (except for excised and cured non-melanoma skin cancer, carcinoma in situ of breast or cervix, superficial bladder cancer, or T1a or T1b prostate cancer comprising \< 5% of resected tissue with normal prostate specific antigen (PSA) since resection). * Major surgery within 6 weeks prior to Study Day 1 (subjects must have completely recovered from any previous surgery prior to Study Day 1). * Active infection requiring antibiotics or antifungals within 7 days prior to first dose of study drug. * HIV-positive patients receiving combination anti-retroviral therapy are excluded from the study because of possible drug interactions with study drugs. Appropriate studies will be undertaken in patients receiving combination anti-retroviral therapy when indicated. Note: HIV testing is not required for entry into this protocol. * Women must not be pregnant or breastfeeding because chemotherapy and/or ficlatuzumab may be harmful to the fetus or the nursing infant. Pregnant women are excluded from this study because chemotherapy and/or ficlatuzumab have the potential for teratogenic or abortifacient effects.