A Phase II Trial of Proton Pump Inhibitors With Chemotherapy in Patients With Metastatic Head and Neck Cancer

Inclusion Criteria: * Males and non-pregnant, non-lactating females at least 18 years old. * Histologically or cytologically confirmed diagnosis of SCCHN (Squamous Cell Carcinoma of the Head and Neck). * Stage IVC (metastatic) or advanced, locally recurrent SCCHN not amenable to curative surgery or radiotherapy. * Measurable disease as defined by RECIST (Response Evaluation Criteria in Solid Tumors) vs 1.1 (Appendix 1). a. If the only site of measurable disease for this study is within a prior field of irradiation, then the sum of the longest diameters (SLD) of that lesion must have increased by at least 20% from the prior treatment nadir. * ECOG Performance status (measure of health and general well being on a scale of 0 to 5 where 0 represents perfect health) \< 1 (Appendix 2). * Expected survival of at least 3 months. * Adequate liver and renal function that is defined as Calculated creatinine clearance of \<30ml/min (by Jelliffe calculator) AST (aspartate aminotransferase)/ALT (alanine aminotransferase) \< 2.5 X ULN (unless there are hepatic metastasis, in which case AST/ALT within 5 X ULN) Total Bilirubin \< 1.5 X ULN (Appendix 5). * Ability to understand and willingness to sign an informed consent form. * Willingness and ability to comply with study procedures and follow up. * There is no restriction on number of prior therapies as long as the patient is deemed a candidate for palliative chemotherapy with one of the standard chemotherapy regimens. * Willingness to use contraception by a method that is deemed effective by the Investigator by both male and female patients of childbearing potential and their partners throughout the treatment period and for at least 30 days following the last cycle of chemotherapy (post menopausal women must have been amenorrheal for at-least 12 months to be considered of non-childbearing potential). Exclusion Criteria: * Comorbidities precluding treatment with combination chemotherapy or per investigator discretion. * Pregnancy or lactation. * Medical or psychiatric illness that may compromise the patient's ability to tolerate the treatment or comply with the study requirements. * Patients with another active cancer or history of another cancer in the last 3 years except those treated with curative intent such as skin cancer (other than melanoma), in situ breast or in situ cervical cancer or those treated with curative intent for any other cancer with no evidence of disease for 2 years. * Allergy to PPI or inability to tolerate PPI. * Patients residing in prison. * Any investigational drug dose within 28 days of planned start of trial. * Any concurrent standard therapy intended to treat SCCHN. * Any symptomatic infection (bacterial, fungal or viral) as per the investigator discretion. * Patients with uncontrolled CNS (Central Nervous System) metastases are excluded. Patients with known, previously treated CNS metastases are eligible if they are neurologically stable as per the investigating physician's clinical assessment. * Any other condition or circumstance that would, in the opinion of the Investigator, make the patient unsuitable for participation in the study. * Patients on Rilpivirine, Atazanavir, Indinavir and Nelfinavir will not be eligible for participation in study because of the significant drug interaction unless the patient can be switched to a different antiviral medication prior to study enrollment. * Omeprazole can increase the serum concentration of methotrexate, clorazepate and citalopram increasing the risk of adverse effects. * Omeprazole may result in reduction in clinical efficacy of clopidogrel and increased risk for thrombosis. * Omeprazole when co-administered with dasatinib, bosutinib, ponatinib, erlotinib, dabrafenib and vismodegib reduces the systemic exposure to these drugs, therefore patients on these drugs should not be enrolled in the study.