Abstract C003: 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
Authors: Khorasanchi Adam , Abushahin Laith , Noonan Anne M , Jin Ning , Hays John , Malalur Pannaga G , Rahman Shafia , Cloyd Jordan , Dillhoff Mary , Tsai Susan , Mittra Arjun , Manne Ashish 
Published: September 2024

Abstract
In this trial, we propose to study the effect of Tumor Treating Fields (TTFields) perioperatively in pancreatic ductal adenocarcinoma (PDAC). There is a growing body of in vitro and in vivo evidence of significant anti-proliferative effects of TTFields on multiple tumor types. The central mechanism is that electromagnetic fields provide bi-directional forces on highly polar intracellular elements, eliciting abnormal microtubule polymerization during spindle formation and aberrant cleavage furrow formation. The safety and efficacy of TTFields concomitant with chemotherapy in advanced PDAC was first reported in the PANOVA phase II trial (N=40). No systemic toxicity was attributed to the electrical field therapy, highlighting this modality's remarkable safety profile. The only additional safety concern was a small number of grade 3 device-related dermatitis that was easily managed, consistent with clinical and real-world experience from glioblastoma and mesothelioma. This is a single-arm phase II trial for resectable PDAC (visible pancreatic mass, measurable disease, absence of arterial interface, venous interface of less than or equal to 180°, patent portal splenic confluence, and absence of metastatic disease, including lymphadenopathy outside the surgical basin); eligible patients will receive three cycles of gemcitabine – nabpaclitaxel (G-NP) along with TTFields therapy (expected to wear ≥ 18 hours/day) followed by restaging. Patients will proceed to surgery if suitable for resection, and an additional 3 cycles of G-NP with TTFields therapy will be used post-surgery. This study uses a Bayesian optimal phase 2 (BOP2) design. The primary endpoints are OS at 2 years and resection rate. With a null hypothesis of 40% vs. a target of 60% for OS at 2 years and a null hypothesis of 60% vs. a target of 75% for resection rate. We will have 30 patients and one futility interim analysis at 15 enrolled patients. The study will be terminated early if ≤ 8 patients undergo resection in the first stage. This will yield 83% power and a type I error of 10% with the following stopping. Secondary endpoints include adverse events, overall response rate, TTFields compliance rate, relative dose intensity, and overall survival. The trial opened to enrollment in October 2023 and is accepting patients. The accrual goal is 38. Clinical trial information: NCT05624918.
Citation Format: Adam Khorasanchi, Laith Abushahin, Anne M Noonan, Ning Jin, John Hays, Pannaga G Malalur, Shafia Rahman, Jordan Cloyd, Mary Dillhoff, Susan Tsai, Arjun Mittra, Ashish Manne. 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]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Pancreatic Cancer Research; 2024 Sep 15-18; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(17 Suppl_2):Abstract nr C003.