Abstract CT084: Targeted intra-arterial gemcitabine vs. continuation of IV gemcitabine plus nab-paclitaxel following Induction with sequential IV gemcitabine plus nab-paclitaxel and radiotherapy for unresectable locally advanced pancreatic cancer (TIGeR-PaC) - phase III trial interim analysis
Authors: Pishvaian Michael , Zureikat Amer , Lopez Charles , Meredith Kenneth , Zervos Emmanuel , Hatoum Hassan , Chung Ki , Berg Daniel J. , Ucar Antonio , Gandhi Ripal , Nazemzadeh Reza , Nainesh Parikh , Novelli Paula , Kouri Brian , Laing Christopher , Boone Brian , Johnson Thor , Bates Susan , Goodman Karyn , Agah Ramtin 
Published: April 2023

Abstract
Background: Treatment of locally advanced pancreatic cancer (LAPC) remains a clinical challenge with a median survival of 16-18 months1. Control of local disease, beyond systemic therapy, is part of the treatment paradigm being investigated in this patient population. Double balloon mediated local delivery of intra-arterial gemcitabine (IAG) into the tumor has been demonstrated to be safe in this patient population2. TIGeR-PaC is an ongoing Phase III clinical trial comparing the efficacy of this approach compared to standard of care IV gemcitabine/nab-paclitaxel (GN) for patients with LAPC.
Methods: The trial is designed with an induction phase for all patients of upfront systemic chemotherapy and radiation prior to randomization to IAG or continuation of GN. ECOG 0-1 LAPC patients receive 3 cycles of GN and 1 cycle of radiation (SBRT, 33 Gy in 5 fractions). Following induction, patients with non-progressive disease are randomized to receive IAG (8 treatments bi-weekly for 16 weeks) or continuation of GN for 4 cycles over 16 weeks. After the 16 weeks of randomized therapy, patients with non-progressive disease receive continuation systemic therapy of GN or low-dose oral capecitabine, per investigator’s preference until disease progression and are followed for survival only. The primary endpoint is the overall survival (OS), and the study is powered at an 80% power to detect a hazard ratio of 0.6 between the two arms. It is assumed that the hazard functions are proportional only during the randomized treatment period, after which the two hazard functions become approximately identical during the continuing treatment period. The primary endpoint of OS for the two treatment arms will be compared using a 2-sided Wilcoxon test. The first interim analysis of the trial for the ITT population is performed after the 26th out of an expected 86 events have occurred in the trial (30%).
Clinical Endpoint Analysis: The first interim analysis of the primary endpoint of OS was conducted on Feb 2nd, 2023. This was based on a data lock on survival status of all patients after the sponsor became aware that the 26th event in the trial occurred on Dec. 21st, 2022. As of that date, 45 patients had been randomized in the trial and the survival status of all 45 subjects was used as of the date for analysis. Of the 45 patients randomized, 23 were randomized to IAG and 22 to continuation of IV GN. There were equal number of primary events, 13, in each arm. The median survival in the control arm is 10 months, versus 16 months in the IAG arm. The p-values based on Wilcoxson non-proportional hazard ratio is 0.051 between the 2 arms. The study continues to accrue patients with a second interim analysis (after 52 events) expected at end of 2024.
1. Hammel P, Huguet F, van Laethem JL, et al. Effect of Chemoradiotherapy vs Chemotherapy on Survival in Patients With Locally Advanced Pancreatic Cancer Controlled After 4 Months of Gemcitabine With or Without Erlotinib. JAMA. 2016;315(17):1844.
2. Rosemurgy AS, Ross SB, Vitulli PL, et al. Safety Study of Targeted and Localized Intra-Arterial Delivery of Gemcitabine in Patients with Locally Advanced Pancreatic Adenocarcinoma. J Pancreat Cancer. 2017;3(1):58-65.
Citation Format: Michael Pishvaian, Amer Zureikat, Charles Lopez, Kenneth Meredith, Emmanuel Zervos, Hassan Hatoum, Ki Chung, Daniel J. Berg, Antonio Ucar, Ripal Gandhi, Reza Nazemzadeh, Parikh Nainesh, Paula Novelli, Brian Kouri, Christopher Laing, Brian Boone, Thor Johnson, Susan Bates, Karyn Goodman, Ramtin Agah. Targeted intra-arterial gemcitabine vs. continuation of IV gemcitabine plus nab-paclitaxel following Induction with sequential IV gemcitabine plus nab-paclitaxel and radiotherapy for unresectable locally advanced pancreatic cancer (TIGeR-PaC) - phase III trial interim analysis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr CT084.