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): A randomized phase 3 multicenter study.

Abstract

TPS773 Background: Prognosis for locally advanced pancreatic cancer (LAPC) remains dismal even with advances in cancer therapy. Beyond systemic therapies, local disease control is important in these patients. Local double balloon mediated delivery of intra-arterial gemcitabine (IAG) was demonstrated to be safe in this patient population in a prior study1. TIGeR-PaC is an ongoing Phase-3 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 of upfront systemic therapy prior to IAG. Patients with LAPC diagnosed within 6 weeks and ECOG 0-1, receive 3 cycles of GN and 1 cycle of radiation. The form of radiation was either IMRT, 50 Gy in 25 fractions, with concomitant capecitabine or SBRT, 33 Gy in 5 fractions (per site preference). Following induction, patients with non-progressive disease were randomized to receive IAG (8 treatments every two weeks for 16 weeks) or continuing therapy with 4 cycles of GN. After the 16 weeks of randomized therapy, the patients with non-progressive disease went on to continue systemic therapy (GN or capecitabine, per investigator’s preference) until disease progression and then followed for survival only. The primary endpoint is overall survival, and the study has an 80% power to detect a hazard ratio of 0.6 between the two arms. As of September 1st, 2022, 189 patients have been enrolled in the trial. In its initial design the trial expected a 35% drop out rate during the induction phase; however, two years into the trial the actual observed dropout rate was 53%. Beyond progression (22%), the key element of dropout rate was AE/SAE during radiation with IMRT/capecitabine (17%) vs. only 6% with SBRT. To increase accrual of randomized patients, the protocol and the statistical plan were modified to restrict the mode of radiation during induction to SBRT only starting December 2021. Since the modification of the protocol, the dropout rate during induction has decreased to 38%. As of this abstract, 43 patients have been randomized following induction with GN and SBRT. The rate of SAE during active treatment is not different between the 2 arms (20% in each arm), and the most common SAE is GI side effects in both arms. The protocol has a pre-planned interim analysis after 26 events, with 23 events at this writing we expect our first interim analysis later this year. 1. Rosemurgy AS, e al: J Pancreat Cancer. 2017;3(1):58-65. doi:10.1089/pancan.2017.0011. Clinical trial information: NCT03257033 .