Phase II Study of Induction Therapy with Gemcitabine and Nab-Paclitaxel Followed by Consolidation with Mfolfirinox in Patients with Metastatic Pancreatic Cancer.

233 Background: We designed a phase II study to evaluate the efficacy, toxicity and feasibility of administering nab-paclitaxel/gemcitabine (NabP-Gem) followed by mFOLFIRINOX in MPC. Methods: Eligible patients had evidence of untreated MPC with performance status of ECOG 0-1 and adequate organ function. Induction therapy was with Nab-P (125 mg/m2) and Gem (1000 mg/ m2) weekly x 3 every 4 weeks for a maximum of 6 months (6 cycles). mFOLFIRINOX every 2 weeks (Consolidation regimen) was initiated after 6 cycles of the Induction regimen, or earlier in case of progression, and given upto 6 months (12 cycles). The FOLFIRINOX regimen (NEJM,364:1817-25: 2011) was modified to omit the bolus 5FU and requires addition of granulocyte growth factor prophylaxis. A primary endpoint is to increase 1 year survival (n=30) to >70%, (95% confidence intervals for one year survival rate is +/- 20%). Results: As of 9/1/2012, 26 of 30 subjects have been accrued. M/F ratio is 58%/42%, median is 65 years. In 20 patients treated on the induction phase, 75% have a > 90% decrease in CA 19-9 levels. The partial response rate (PR) in the first 19 patients who have completed 4 cycles is 50%. Early image analysis on 9 subjects with concurrent CT and PET showed 44% PR (RECIST 1.1) but 89% by CHOI and PET criteria. A novel approach to interrogate tumor texture composition demonstrated substantial change in lesion texture following induction therapy. To date selected Grade > 3 adverse events are neutropenia (n=8), fatigue (n=5), thromboembolic events (n=4), peripheral neuropathy (n=3), dehydration (n=2), anemia (n=3), thrombocytopenia (n=2), febrile neutropenia (n=2) and myalgias (n=2). Among 26 patients who have received at least one cycle of NabP-Gem, ten dose reductions and four dose delays were seen. To date, 11 patients have begun the Consolidation regimen with mFOLFIRINOX. Conclusions: The induction NabP-Gem regimen shows preliminary evidence of substantial activity similar to published reports (JCO.29:4548-54: 2011). Study will now evaluate the safety, efficacy and feasibilty of the Consolidation regimen with mFOLFIRINOX. Supported by the Seena Magowitz Foundation. Clinical trial information: NCT01488552.