La nanomedicina in oncologia: presente e futuro Alessandro Bittoni Scuola di Dottorato di Ricerca- Clinica di Oncologia Medica AOU Ospedali Riuniti - Università Politecnica delle Marche Ancona La nanomedicina in oncologia: presente e futuro GAP (Gemcitabine Abraxane Pancreas)Trial Bari, 27 Marzo 2015

Background and Rationale Study Design and Objectives Study Populations Enrollment Status Patients’ Characteristics

Background and Rationale About 25-30% of pancreatic cancer pts present with locally advanced disease (LAPC) Chemotherapy followed by chemoradiation is an accepted strategy in this setting Gemcitabine + nab-paclitaxel was shown to be superior in terms of RR, PFS and OS to gemcitabine in stage IV pts No data in LAPC

Study Design and Objectives Phase II, randomized, open-label, multicenter study ARM A nab-paclitaxel + gemcitabine 3 cycles ALL Capecitabine + RT 5 weeks Locally advanced pancreatic cancer R ARM B gemcitabine 3 cycles If PD Second Line Chemotherapy Arm A: nab-paclitaxel 125 mg/mq + gemcitabine 1000 mg/mq days 1-8-15 q28 Arm B: gemcitabine 1000 mg/mq

Study Design and Objectives Primary Endpoint Progression rate after 3 months Secondary Endpoint RR, toxicity, PFS, OS 124 pts required for final analysis 40% vs 20% PR, one-tailored alpha= 0.05, 80% power After 109 events the study will have 80% powe to detect 0.62 HR and 61% to detect 0.69 HR

Main Inclusion Criteria Study populations Main Inclusion Criteria Written informed consent Age < 75 years Histologically/cytologically confirmed locally advanced, unresectable PC At least 1 measureable lesion (RECIST 1.1) ECOG 0-1 Life expectancy of at least 3 months Adequate marrow, liver and renal function

Main Exclusion Criteria Study populations Main Exclusion Criteria Previous chemotherapy or radiotherapy for pancreatic cancer CNS metastases Severe cardiovascular disease Thrombotic or embolic events Acute or subacute intestinal occlusion or history of inflammatory bowel disease Known hypersensitivity to study drug Previous or concurrent malignancies

Enrollment started on 07 February 2014 Enrollment status Enrollment started on 07 February 2014 Enrollment will stop on April 2016 9 patients enrolled aggiornato al 30 Settembre 2014

Enrollment status

Enrollment status

Patients Characteristics

Safety 3 SAE reported

Grazie per l’attenzione!