PANOVA-3: A phase 3 study of TTFields with gemcitabine and nab-paclitaxel for front-line treatment of locally-advanced pancreatic adenocarcinoma (LAPC)

Abstract

Background: TTFields are a non‐invasive, regional antimitotic treatment modality, which has been approved for the treatment of glioblastoma by the FDA. TTFields predominantly act by disrupting the formation of the mitotic spindle during metaphase. TTFields were effective in multiple preclinical models of pancreatic cancer. PANOVA was the first trial testing TTFields in pancreatic cancer patients, demonstrating their safety when combined with gemcitabine and nab‐paclitaxel, and preliminary promising efficacy in LAPC. PANOVA‐3 is designed to test the efficacy of adding TTFields to the same chemotherapy combination in this disease stage. Trial design: Approximately 600 patients with unresectable, LAPC (perNCCNguidelines) will be enrolled in this prospective, randomized trial. Patients should have an ECOGscore of 0‐2 and no prior progression or treatment. Patients will be stratified based on their performance status and geographical region.Gemcitabine and nab‐paclitaxel will be administered at standard dose. TheNovoTTF‐100L (150kHz) systemwill be used by experimental armpatients for at least 18 hours/day until local disease progression per RECIST Criteria V1.1. Follow upwill be performed q8w, including a CT scan of the chest and abdomen. Following local disease progression, patients will be followedmonthly for survival. Overall survival will be the primary endpoint and progression‐free survival, objective response rate, rate of resectability, quality of life and toxicity will all be secondary endpoints.