Randomized Phase II Clinical Trial of AZD6244 Hydrogen Sulfate (NSC-748727) and MK-2206 (NSC-749607) vs. mFOLFOX in Patients with Metastatic Pancreatic Cancer after Prior Chemotherapy

Histologically or cytologically confirmed diagnosis of pancreatic adenocarcinoma (Pts w/endocrine or neuroendocrine tumors, lymphoma of the pancreas, or ampullary cancer are not eligible). Must have distant metastatic disease (pts w/macroscopic residual disease post-resection as only site of disease, significant ascites, or brain mets are not eligible). Must have received only 1 line of prior gemcitabine chemotherapy for pancreatic cancer within 42 days of last treatment OR for patients who received one line of gemcitabine-based chemotherapy in adjuvant settting, recurrence to metastatic site must be documented within 6 months of completing chemotherapy. Must have completed systemic therapy at least 14 days prior to reg, surgery at least 14 days prior to reg, and radiation therapy at least 7 days prior to reg. Must not plan to receive concurrent chemotherapy, radiotherapy, agents know to prolong QTc interval, or strong CYP3A4/5 or CYP1A2 inhibitors/inducers. No prior treatment with FOLFIRINOX, FOLFOX, MEK inhibitors, PI3K inhibitors, or AKT inhibitors. Measurable and/or non-measurable disease. Zubrod performance status 0-1. H&P obtained within 28 days of reg. Within 14 days of reg: leukocytes >/= 3,000/mcL; ANC >/= 1,500/mcL; platelets >/= 100,000/mcL; hemoglobin >/= 9.0; serum creatinine </= 1.5 mg/dl OR calculated creatinine clearance >/= 60 ml/min; total bilirubin </= 1.5x IULN; AST and ALT both </= 2.5 x IULN; albumin >/= 3.0 g/dL; INR </= 1.5 x IULN. Must have ECG within 14 days prior to reg and QTcF </= 450 msec (male) or </= 470 msec (female). Baseline neuropathy must be </= Grade 1 according to CTCAE v4.0.Must not have uncontrolled diarrhea or active infection within 7 days prior to reg. Must be able to swallow pills and capsules. Pts with diabetes must be well controlled with fasting glucose </= Grade 1 according to CTCAE v4.0 within 14 days prior to reg. Pts with history of congestive heart failure must have ejection fraction >/= 55% within 14 days prior to reg. Must not have: uncontrolled hypertension, acute coronary syndrome within 6 months prior to reg; poorly controlled angina; New York Heart Association Class II-IV heart failure; prior or concurrent cardiomyopathy; atrial fibrillation; or severe valvular heart disease. Must not have current or past history of central serous retinopathy, retinal vein occlusion, retinal detachment, or have uncontrolled glaucoma (irrespective of IOP). No other prior malignancy is allowed except the following: adequately treatment basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated Stage I or II cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease-free for five years. Must not be pregnant or nursing.