Summary Between October 2008 and December 2009 18 patients were accrued

1. Primary Objective 1.1.1.1 To determine the maximum tolerated dose (MTD) of nab-paclitaxel when combined concurrently with carboplatin and radiation followed by two cycles of nab-paclitaxel/carboplatin as consolidation A Phase II Trial of Sorafenib (S) and Erlotinib (E) in Unresectable Pancreas Cancer (UPC): Preliminary Results 1DC Backlund, 1LW Goff, 1E Chan, 1Y Shyr, 2WA Conkright, 1L Cornelius, 1S Pakron,1 M Holloway, 1P McClanahan, 1J Berlin. 1Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN; 2Purchase Cancer Group, Paducah, KY. ( • Trial Design • Methods • Phase II, nonrandomized, single arm, multiinstitutional study • Inclusion Criteria • Microscopic confirmation of diagnosis of unresectable pancreatic adenocarcinoma (excluding neuroendocrine tumors and cystadenocarcinoma) • Measurable or evaluable disease by RECIST criteria • Age > 18 years • ECOG PS 0-2 • Adequate bone marrow, liver and renal function • Normal coagulation parameters in pts not receiving anticoagulants such as warfarin or heparin • Exclusion Criteria • Prior treatment with antiangiogenics • Patients who received more than one line of therapy for advanced disease • Underlying heart failure > class II NYHA, unstable angina or MI in prior 6 months • Ventricular arrhythmias requiring antiarrhythmic therapy • Uncontrolled hypertension • Known HIV or chronic Hepatitis B or C • Any arterial thrombotic event in prior 6 months • Pulmonary hemorrhage or other bleeding event within 4 weeks of beginning study drug, or prior evidence of a bleeding diathesis or coagulopathy (except cancer-related blood clots) • Serious non-healing wound, infection, ulcer or bone fracture • Known brain metastasis • Patients who require therapy with known strong CYP3A4 inhibitors or inducers • Major surgery, open biopsy or significant traumatic injury within 4 weeks of first study drug • Known allergy to sorafenib or erlotinib • A known, untreated malabsorption problem, or inability to swallow whole pills • Pregnant or nursing women Patient Demographics Toxicity Abstract Background: The MAP kinase pathway is known to play a central role in PC pathogenesis, and blocking this pathway at multiple levels using S and Eis attractive from a mechanistic standpoint. S also targets VEGF receptors and there is evidence suggesting that blockade of both EGFR and VEGF pathways simultaneously has potential for additive, if not synergistic effects. This phase II trial is designed to evaluate the efficacy of the combination of S andEin patients with UPC. Methods: Patients (pts) with UPC are eligible to receive S 400mg twice daily along with E 150mg once daily, on a continuous basis as either 1st or 2nd line therapy. Primary endpoint is 8-week progression free survival rate (PFS) and secondary endpoints include response rate, 4-month PFS and safety. In addition, DNA from peripheral blood will be interrogated by analysis of single nucleotide polymorphisms to see if any predict for response and toxicity with these agents. Results: Fourteen pts have enrolled to date, and 13 have received study drug. Median age is 62 (range 52-75), 8 female, 6 male. Thirteen patients have received prior regimens, and 3 pts had ECOG PS=2 upon starting therapy. Grade 3 related toxicities reported thus far include nausea, vomiting and abdominal pain (4 pts each), diarrhea (3 pts), hypertension, constitutional symptoms and low blood counts (2 pts each), and 1 pt each with rash, constipation and dehydration. There have been 7 deaths, all due to progressive disease. Eleven pts were off-treatment at the time of this assessment, 7 due to disease progression, 2 due to pt request or withdrawal, and 2 due to toxicities or complications. Conclusions: The combination of full-dose S andE is often poorly tolerated by UPC pts, and this protocol has been amended to begin pts at an S dose of 400mg q day. For several patients, there was a delay in start of therapy due to problems getting insurance coverage for erlotinib on study, and for patients with aggressive disease, this delay may have had an impact on tolerance of therapy and survival. Efficacy data and toxicity of the revised dosing regimen will be reported at the meeting after an interim analysis. Data included in this poster reflects updated information since abstract submission. • Summary • Between October 2008 and December 2009 18 patients were accrued • Full dose sorafenib and erlotinib were poorly tolerated in this patient population, with 12 of the first 15 patients accrued requiring dose delays or dose reductions. This protocol has been amended to begin sorafenib at a lower dose, (400mg qd) with option of titration to full dose if patient tolerates modified dose well after one month of combined therapy • Toxcities seen in this patient population appear slightly more severe than in the lung cancer population reported by Lind, et al • There were no unanticipated toxicities seen in this study, and no deaths to date attributable to study interventions • It is too early to draw conclusions regarding efficacy. Trial accrual is ongoing at the modified dose. Results to Date Efficacy **Research support provided by Bayer-Onyx Pharmaceuticals; additional drug support provided by OSI Pharmaceuticals. This research was also supported by the Vanderbilt-Ingram Cancer Center Support Grant CA 068485-14. • Objectives • Primary: To determine the efficacy of the combination of sorafenib and erlotinib in patients with unresectable pancreas cancer. Primary endpoint is 8-week progression free survival rate. • Secondary: To determine the response rate, the progression free survival at 4 months, and evaluate the safety profile of this combination in this patient population. • Correlative: To evaluate change in serum Ca 19-9 at baseline and at 8-week intervals, to gather blood and plasma at baseline and 8 weeks for future DNA and proteomic assessments.