Trial in Progress: 2019-1001 A Phase I Study of NBTXR3 Activated by Radiotherapy for Locally Advanced or Borderline Resectable Pancreatic Ductal Adenocarcinoma (LAPC or BRPC)

Abstract

<h3>Purpose/Objective(s)</h3> Patients with pancreatic ductal adenocarcinoma (PDAC), who are not eligible for surgery after induction chemotherapy often receive radiation. Although radiation therapy (RT) improves local disease control, the placement of the pancreas proves to be difficult when safely delivering therapeutic doses. NBTXR3 is a novel, potentially first-in-class radio enhancer, composed of functionalized hafnium oxide nanoparticles that is administered via one-time intratumoral injection and activated by RT. Pre-clinical testing suggests up to a 9-fold enhancement of the RT dose delivered within tumor cells. In this phase 1 trial-in-progress, the primary objective is to determine the recommended phase II dose (RP2D) of NBTXR3 for LAPC and BRPC patients undergoing RT. The secondary objectives are to evaluate the safety, feasibility, and anti-tumor response of NBTXR3 intratumoral injection on PDAC patients as well as time-to-event outcomes of subjects. <h3>Materials/Methods</h3> For the dose-finding part 1 of the study, patients with LAPC and no metastatic disease after at least 2-6 months of chemotherapy will be eligible. For part 2, the expansion at RP2D, patients with BRPC or LAPC and no metastatic disease after chemotherapy will be eligible. The statistical design of the trial uses a Bayesian optimal interval (BOIN) design. A maximum of 24 patients will be enrolled. For baseline and follow-up, imaging and blood biomarkers will be collected. Patients enrolled will receive NBTXR3, once, through intratumoral injection via endoscopic ultrasound (Day 1). Pre-treatment biopsy will be collected. Post NBTXR3 injection, blood samples will be collected at 4 time points (0,5,30, and 120 minutes). Two urine voids will be collected post injection for hafnium quantification as well. At least three days later, patients will undergo imaging for RT dosimetry and planning where NBTXR3 can be visualized. Patients will then receive 45 Gy in 15 fractions with IMRT, with regional nodal basins receiving 37.5 Gy. Follow-up period will begin 4 weeks after end of treatment and continue every 3 months for a year. Patients will be evaluated for surgery 4-12 weeks post RT. At 11-13 weeks after end of RT, if the patient is not eligible for surgery, an endoscopic ultrasound procedure will be performed. In both events, a post-treatment biopsy will be obtained. The imaging collected of pancreatic target lesion will be used to determine tumor response as per RECIST v1.1 criteria. <h3>Results</h3> Trial is open and accruing, with 8 patients enrolled so far. <h3>Conclusion</h3> We expect to determine the RP2D, safety, and preliminary efficacy of NBTXR3 in pancreatic cancer with this study with blood, tissue, and imaging correlates in 2022.