P-186 - International phase II trial of weekly nab-paclitaxel (nab-P) plus gemcitabine (Gem) in patients with locally advanced pancreatic cancer (LAPC): LAP...

Date 04 July 2015
Event WorldGI 2015
Session Posters
Topics Anti-Cancer Agents & Biologic Therapy
Pancreatic Cancer
Presenter Philip A. Philip
Citation Annals of Oncology (2015) 26 (suppl_4): 1-100. 10.1093/annonc/mdv233
Authors P.A. Philip1, P. Hammel2, L. Kayitalire1, T. Nydam1, D. Penenberg3
  • 1Karmanos Cancer Center, Detroit/US
  • 2Hôpital Beaujon, Clichy/FR
  • 3Celgene, Summit/US

Abstract

Introduction

Treatment strategies for patients with LAPC include both systemic therapy and local treatment (eg, radiation or surgery). A systemic therapy that induces substantial tumor shrinkage may improve local control of the disease and potentially increase survival. Gem is considered a standard of systemic therapy in LAPC. In the MPACT trial, nab-P + Gem demonstrated significantly longer overall survival (OS, primary endpoint) than Gem alone in patients with metastatic PC (median, 8.7 vs 6.6 months; HR 0.72; P < 0.001). Local PC control was observed with an approximate 3-fold greater shrinkage of primary pancreatic tumors vs Gem alone. The LAPACT study will assess the efficacy and safety of first-line nab-P + Gem in LAPC.

Methods

This open-label, multicenter phase II trial will enroll approximately 110 patients in the United States, Canada, and Europe. Patients with Eastern Cooperative Oncology Group performance status ≤ 1, histologically or cytologically confirmed LAPC that is unresectable according to radiographic criteria or exploration, adequate organ function, and no distant metastases are eligible. Key exclusion criteria include histology other than adenocarcinoma, prior therapy for PC, any other malignancy within 5 years, peripheral neuropathy grade > 1, and clinically significant ascites. Eligible patients will receive first-line therapy with nab-P 125 mg/m2 plus Gem 1000 mg/m2 on days 1, 8, and 15 of each 28-day cycle. After 6 cycles, patients without disease progression or unacceptable toxicities will receive investigator's choice of surgery, chemoradiotherapy (Gem or capecitabine with radiation), or continuation of nab-P + Gem. Surgery may occur prior to completing the planned 6 cycles of nab-P + Gem if a major response is observed. Patients will be followed until disease progression, withdrawal of consent, lost to follow-up, or death. The primary endpoint is time to treatment failure (TTF), defined as the time from the first dose of study therapy to discontinuation due to disease progression, start of a new non–protocol-defined anticancer therapy, or death. The study design will allow 80% power at a 1-sided alpha of 0.05 to detect a 30% increase in median TTF over the 5.1-month median TTF observed for nab-P + Gem in the phase III MPACT study. Secondary endpoints include disease control rate after 6 cycles, overall response rate, progression-free survival, OS, safety, and health-related quality-of-life outcomes as assessed by the European Organisation for Research and Treatment of Cancer questionnaires QLQ-C30 and QLQ-PAN26. Correlation of changes in circulating nucleic acids with disease progression and response to treatment will be evaluated as an exploratory endpoint. An interim analysis of disease control rate is planned after all patients have completed 6 cycles of nab-P + Gem, discontinued therapy due to disease progression, died from any cause, or started a new non–protocol-defined therapy prior to completing 6 cycles of therapy. Enrollment is ongoing. ClinicalTrials.gov: NCT02301143.