A phase II trial of perioperative tumor treating fields (NovoTTF-200T[P]) combined with gemcitabine and nab-paclitaxel in resectable pancreatic adenocarcinoma: Big Ten Cancer Research Consortium (BTCRC-GI21-500).

Abstract

TPS797 Background: Resectable pancreatic ductal adenocarcinoma (R-PDA) continues to be associated with high recurrence and poor long-term outcomes. While neoadjuvant chemotherapy is increasingly utilized, its superiority over upfront resection with adjuvant therapy remains uncertain. Tumor treating fields (TTFields) exert anti-mitotic effects by disrupting microtubule assembly and impairing cytokinesis through alternating electric fields. Preclinical models and clinical data suggest additive activity with chemotherapy. In the phase II PANOVA trial (n=40) in advanced PDA, TTFields combined with gemcitabine-based therapy demonstrated promising activity with acceptable safety, the main device-related adverse event being grade 3 dermatitis. Methods: This multicenter, single-arm phase II trial will assess perioperative TTFields in combination with gemcitabine plus nab-paclitaxel (GNP) in patients with R-PDA. Key eligibility criteria include: visible pancreatic mass, measurable disease, ≤180° venous involvement without arterial encasement, patent portal–splenic confluence, and no distant metastasis or extra-regional lymphadenopathy. Patients will initiate treatment with TTFields (compliance goal >80%) and three cycles of GNP, followed by restaging. Those proceeding to resection will receive an additional three cycles of adjuvant GNP with TTFields. The Bayesian Optimal Phase II (BOP2) design specifies dual primary endpoints: 2-year overall survival (OS) and resection rate. The null hypotheses are OS of 40% (vs. 60% target) and resection rate of 60% (vs. 75% target). A total of 30 evaluable patients are required, with an interim analysis after 15 patients; early termination occurs if ≤8 resections are achieved at that point (power 83%, type I error 10%). Secondary objectives include safety/tolerability, overall response rate, TTFields compliance, relative dose intensity, and long-term survival outcomes. The study opened to accrual with a planned enrollment of 38 patients. At the time of submission, two patients had been enrolled, and one patient had resection (ClinicalTrials.gov identifier: NCT05624918). Clinical trial information: NCT05624918 .