APACT: Phase III randomized trial of adjuvant treatment with nab-paclitaxel (nab-P) plus gemcitabine (Gem) versus Gem alone in patients (pts) with resected pancreatic cancer (PC).

Abstract

TPS473 Background: Gem therapy improves outcomes in pts with resected PC. However, disease recurrence is common, prompting a need for improved regimens. nab-P + Gem was superior to Gem alone in MPACT, a phase III trial of pts with metastatic PC (mPC) for all endpoints, including overall survival (OS; median, 8.7 vs 6.6 months; hazard ratio [HR] 0.72; P < 0.001). Toxicities were manageable and consistent with prior studies. The APACT trial will compare adjuvant nab-P + Gem vs Gem alone in pts with resected PC. Methods: Pts (≈ 800) with confirmed PC (R0 or R1 resection); stage T1 - 3, N0 - 1, M0; Eastern Cooperative Oncology Group performance status ≤ 1; adequate organ function; and CA19-9 < 100 U/mL within 14 days of randomization are eligible. Pts with mixed-origin tumors; present or previous mPC; any other malignancy within 5 years of randomization; HIV or hepatitis B or C infection; or prior neoadjuvant treatment or radiotherapy for PC are ineligible. Randomization should occur once pts adequately recover from surgery but ≤ 12 weeks after surgery. Pts will receive 6 cycles of either nab-P 125 mg/m2 plus Gem 1000 mg/m2 or Gem 1000 mg/m2 on days 1, 8, and 15 of a 28-day cycle. Stratification factors are resection (R0 vs R1) and nodal (LN+ vs LN−) status and geographic region (North America vs Europe vs Australia vs Asia Pacific). Pts with > 2 dose reductions will be discontinued. The primary endpoint is independently assessed disease-free survival (DFS). Secondary endpoints are OS and safety. Quality of life and correlation of tumor heterogeneity with clinical outcome are exploratory outcomes. At least 489 DFS events from 800 pts will allow 90% power to detect an HR for DFS of 0.74 at a 2-sided significance level of 0.05. Interim analyses, 1 for safety (after 100 pts are treated for ≥ 2 cycles) and 2 for efficacy (the first for futility and the second for futility and superiority), will be performed. As of July 2015, > 400 pts were enrolled, and 80% of all activated study sites (n = 141) randomized ≥ 1 pt. Of the 674 screened pts, ≈ 25% were ineligible, mainly due to postsurgical disease recurrence identified at screening. Pt enrollment is ongoing. ClinicalTrials.gov: NCT01964430. Clinical trial information: NCT01964430.