A Study of Entinostat and FOLFOX in Subjects With Pancreatic Adenocarcinoma

Exclusion Criteria

• •Subjects with known or suspected brain metastasis
• •Significant cardiovascular disease such as New York Heart Associate Class III/IV, cardiac failure, myocardial infarction within 6 months prior to enrolment, unstable arrhythmia, or evidence of ischemia on ECG.
• •Baseline QTc exceeding 450msec (470msec for females) and / or subjects receiving class 1A or class III anti-arrhythmic agents.
• •Known HIV or active hepatitis A, B or C infection (with positive viral PCR).
• •Malignancies other than pancreatic cancer ≤5 years prior to Entinostat and FOLFOX cycle 1 day 1, with the exception of those with a negligible risk of metastasis or death and treated with expected curative outcomes (such as adequately treated carcinoma in situ of the cervix, basal or squamous cell skin cancer or ductal carcinoma in situ treated surgically with curative intent) or localized prostate cancer treated with curative intent and absence of PSA relapse or incidental prostate cancer (Gleason score ≤3 +4 and PSA \<10ng/L undergoing active surveillance and treatment naïve).
• •Severe infections ≤ 4 weeks prior to enrolment in the study as well as active, uncontrolled bacterial, viral or fungal infections requiring systemic treatment.
• •Major surgical procedure ≤ 2 weeks prior to enrolment or anticipation of need for a major surgical procedure during the course of the study other than for diagnosis.
• •Treatment with chemotherapy or other investigational agents within 28 days (or at least 5 x the half-life of the drug) prior to day 1 cycle 1 of Entinostat and FOLFOX (6 weeks for nitrosoureas or Mitomycin C).
• •Concurrent treatment with other experimental drugs or participation in another clinical trial with any investigational medicinal product (IMP) within ≤ 5 x the half-life of the IMP prior to day 1 cycle 1 of Entinostat and FOLFOX.
• •Any other disease, metabolic dysfunction, physical examination finding or clinical laboratory finding that, in the investigator's opinion, gives reasonable suspicion of a disease or condition that contraindicates the use of Entinostat or FOLFOX, may affect the interpretation of the results, render the subject at high risk from treatment complications or interferes with obtaining informed consent.
• •Female subjects who are pregnant or nursing.
• •Pre-existing neuropathy \> CTCAE Grade 2
• •Previous treatment with platinum agents
• •Allergy to benzamide or inactive components of entinostat
• •Any contraindication to oral agents or significant nausea and vomiting, malabsorption or significant small bowel resection that, in the opinion of the investigator, would preclude adequate absorption.