P-272 The international, open-label, multicenter phase 2 LAPACT trial of nab-paclitaxel (nab-P) plus gemcitabine (Gem) for patients with locally advanced pancreatic cancer (LAPC)

Abstract

Introduction: Efficacious systemic therapies for LAPC may be associated with improved local disease control and overall survival (OS). The phase 3 MPACT trial in patients with previously untreated metastatic PC demonstrated longer OS (median, 8.7 vs 6.6 months; hazard ratio 0.72; P < 0.001) and an 3-fold greater shrinkage of primary pancreatic tumors with nab-P + Gem vs Gem alone (-22.15% vs -7.02%), which suggests the potential for improved local PC control with this combination. The LAPACT trial will evaluate efficacy and safety of nab-P + Gem in treating patients with LAPC. Methods: Trial Design The LAPACT trial will enroll 110 patients in the United States, Canada, and Europe. Patients with no prior therapy for PC; an Eastern Cooperative Oncology Group performance status of 0 or 1; confirmed unresectable LAPC (adenocarcinoma only, no endocrine or mixed-origin tumors); no distant metastases; and adequate organ function are eligible. Patients with a history of metastatic PC; any other malignancy within 5 years; peripheral neuropathy grade > 1; allergy or hypersensitivity to nab-P, Gem, or any of their excipients; or clinically significant ascites are ineligible. Patients will receive 6 cycles of nab-P 125 mg/m2 + Gem 1000 mg/m2 on days 1, 8, and 15 of each 28-day cycle. After 6 cycles, patients without progressive disease (PD) or unacceptable toxicity will receive investigator's choice of continuing nab-P + Gem, chemoradiation (Gem or capecitabine with radiation according to institutional practice), or surgery. Surgery may occur prior to completion of 6 cycles of nab-P + Gem if a major response is observed. The primary endpoint is time to treatment failure (TTF; time from first therapy dose to discontinuation due to PD, start of a new non-protocol-defined anticancer therapy, or death [from any cause]). The study design allows for 80% power at a 1-sided of 0.05 to detect a 30% increase in median TTF from 5.1 (median observed for nab-P + Gem in the MPACT study) to 6.6 months. The secondary endpoints are disease control rate (DCR) after 6 cycles of nab-P + Gem, overall response rate, progression-free survival, OS, safety, and quality of life (by European Organisation for Research and Treatment of Cancer [EORTC] quality-of-life questionnaires [QLQs] QLQ-C30 and QLQPAN26). The exploratory endpoint is to correlate changes in circulating nucleic acids with PD and treatment response to continued nab-P + Gem or nab-P + Gem followed by chemoradiation. An interim analysis of the DCR will occur after all patients have completed 6 cycles of nab-P + Gem, discontinued therapy due to PD, died (from any cause), or started a new non-protocol-defined therapy before completing 6 cycles of therapy. The trial has enrolled over 50% of the planned patient population and enrollment is ongoing. ClinicalTrials.gov: NCT02301143. Results: Conclusion:.