PANOVA-3: A phase 3 study of tumor treating fields with gemcitabine and nab-paclitaxel for front-line treatment of locally advanced pancreatic adenocarcinoma.

TTFields are an antimitotic therapy delivering low-intensity, intermediate-frequency, alternating electric fields non-invasively to the tumor region via arrays placed on the skin. The phase 2 PANOVA study demonstrated the safety and preliminary efficacy of TTFields when combined with GnP in metastatic and locally advanced pancreatic adenocarcinoma (LAPC). The phase 3 PANOVA-3 trial (NCT03377491) will evaluate the efficacy and safety of adding TTFields to GnP in LAPC. This prospective, randomized trial is enrolling untreated patients (N = 556) with unresectable LAPC and an eastern cooperative oncology group performance status (ECOG PS) score of 0–2. Patients will be randomized 1:1 to TTFields plus GnP or GnP alone, stratified by ECOG PS and geographical region. GnP will be administered at standard doses (nab-paclitaxel 125 mg/m2; gemcitabine 1000 mg/m2) on Days 1, 8, and 15 of a 28-day cycle. TTFields (150 kHz) will be delivered at least 18 h/day until disease progression per RECIST criteria V1.1. A recent protocol amendment incorporated use of a smaller device (weight reduced from 6 to 2.7 lbs). Computed tomography scans will be performed every 8 weeks. The primary endpoint is overall survival. Secondary endpoints include progression-free survival, objective response rate, rate of resectability, quality of life, and toxicity. Sample size was calculated using a log-rank test comparing time to event in patients treated with TTFields plus GnP versus GnP alone. PANOVA-3 is designed to detect a hazard ratio 0.75 in overall survival. Type I error is set to 0.05 (two-sided) and power to 80%.