A phase II study of peri-operative NovoTTF-200T(P) in combination with gemcitabine and nab-paclitaxel for resectable pancreatic adenocarcinoma: Big Ten Cancer Research Consortium (BTCRC-GI21-500).

Abstract

TPS795 Background: The recurrence rates and outcomes in resectable pancreatic ductal adenocarcinoma (R-PDA) is concerningly high. The benefit of neoadjuvant chemotherapy over traditional upfront surgery followed by adjuvant therapy is not clear. Electromagnetic fields generate bi-directional forces on highly polar intracellular components, causing abnormal microtubule polymerization during spindle formation and irregular cleavage furrow formation. We will leverage these anti-proliferative effects in managing R-PDA by tumor treating fields (TTF) with chemotherapy backed by strong in vitro and in vivo evidence. The PANOVA phase II trial (n=40) gave us safety and efficacy data of this combination in advanced PDA. No systemic effects were associated with TTF. The only notable safety issue was a small incidence of grade 3 device-related dermatitis. Methods: Our phase II single arm study will investigate perioperative use of TTF with gemcitabine and nab-paclitaxel (G-NP) combination. Eligible patients R-PDA (visible pancreatic mass, measurable disease, absence of arterial interface, venous interface ≤ 180°, patent portal splenic confluence, and no metastatic disease, including lymphadenopathy outside the surgical area) will wear TTF and receive three cycles of G-NP before restaging. Patients are expected to wear TTF for > 80% of the time during this period. If they proceed with resection, additional 3 cycles of Gem-NP with TTF will be given to the patient. This study employs a Bayesian Optimal Phase 2 (BOP2) design with primary endpoints of overall survival (OS) at 2 years and resection rate. The null hypothesis posits a 40% OS rate compared to a target of 60%, and a resection rate null hypothesis of 60% versus a target of 75%. The trial aims to enroll 30 patients, with an interim futility analysis planned after 15 participants. Enrollment will be terminated early if 8 or fewer patients undergo resection in the initial stage, providing 83% power and a type I error rate of 10%. Secondary endpoints include adverse events, overall response rate, TTFields compliance rate, relative dose intensity, and overall survival. The trial started actively recruiting patients in April 2024. The accrual goal is 38 patients. At the time of submission, one patient was enrolled. Clinical trial information: NCT05624918 .