Phase I Study of PTM-101 As Neoadjuvant Therapy for Borderline Resectable or Locally Advanced Pancreatic Ductal Adenocarcinoma: A Trial in Progress.

TPS775 Background: While there have been tremendous advances in cancer treatment, critical challenges remain including limited ability of drugs to successfully reach the tumor, short half-life, and low retention rate on site. Local control of non-metastatic pancreatic adenocarcinoma (PDAC) remains a major challenge. Up to 40% of patients present with locally advanced and borderline resectable anatomy, for whom enhanced local downsizing of disease could improve symptoms and increase overall survival (OS). Targeted therapies with reduced systemic toxicity are needed for the treatment of PDAC since current therapies have not provided meaningful advances. PTM-101 is a paclitaxel-impregnated absorbable product which is designed for direct, sustained release of the therapeutic agent at the tumor site. Preclinical animal studies demonstrate that PTM-101 results in enhanced drug levels in the tumor compared with comparable systemic paclitaxel dosing leading to tumor reduction, metastasis inhibition and survival benefit (Indolfi et al, 2016). Large animal (i.e. pigs) and human cadaver studies show that PTM-101 can successfully be deployed to the peritumoral pancreatic surface by a standard laparoscopic procedure. Further, large animal studies show no evidence of neutropenia, pancreatitis, severe fibrosis or scarring, or infection after placement of PTM-101. Methods: This Phase I trial will assess the addition of PTM-101 prior to mFOLFIRINOX in 6 subjects with newly diagnosed borderline resectable or locally advanced PDAC. The primary objective is to assess the safety, toxicity and feasibility of a single administration of PTM-101. It is hypothesized that PTM-101 will be readily implanted during diagnostic laparoscopy and will result in clinically meaningful delivery of paclitaxel directly towards the tumor area with good tolerance and minimal local systemic exposure of drug. Patients enrolled and treated on study will be monitored closely for local and systemic toxicities as well as preliminary signals of efficacy. Enrollment is in progress and 3 patients have been enrolled and completed prospective follow up at the time of abstract submission. Clinical trial information: ACTRN12621000881831 .