Diez, Pedro Quintana

284 Background: ODSH, a low anticoagulant heparin derivative, interferes with several important pancreatic cancer cell survival pathways. A randomized phase II trial was initiated to determine if ODSH improves the activity of G/A, a promising pancreatic cancer investigational therapy. Preliminary data are presented here for the first 10 patients administered ODSH as part of an initial run-in phase prior to patient randomization. Methods: Patients with previously untreated, metastatic pancreatic cancer were treated with G (1,000 mg/m2) and A (125 mg/m2) plus ODSH (4 mg/kg bolus followed by a 48 hr. continuous IV infusion at a dose of 0.375 mg/kg/hr) on days 1, 8, and 15 every 28 days until disease progression or unacceptable toxicity. Patients were required to have ECOG ≤ 1 and appropriate blood and liver function levels. The primary endpoint was progression-free survival (PFS). Results: 10 patients (median age, 66 years) were administered up to 5 cycles of G/A plus ODSH. Per RECIST criteria, a partial response (PR) was achieved in 5 patients (50%) and the median PFS will exceed 6 months. Disease control (PR or stable disease for > 16 weeks) occurred in all 10 patients. Of 9 patients with baseline elevated CA 19-9 levels, 8 had > 60% reduction. ODSH was well tolerated and unexpectedly appeared to preserve marrow function as no patients had grade 3/4 thrombocytopenia or grade 4 neutropenia during any of the cycles. Conclusions: Although G/A and FOLFIRINOX are important advances, additional progress is necessary for metastatic pancreatic cancer patients. ODSH may interfere with pancreatic cancer invasion, metastasis, and chemo-resistance by inhibiting P- and L-selectins, heparanase, and the HMGB1-RAGE axis, respectively, suggesting that ODSH may enhance chemotherapy activity. This preliminary analysis in a small number of patients is encouraging and consistent with a previous report for this regimen (Von Hoff, J Clin Oncol, 2011). ODSH has also been very well tolerated and early data suggests that it may preserve platelet and neutrophil levels. Further follow-up of the ongoing randomized phase II trial is warranted. Clinical trial information: NCT01461915.