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Sa2006 EUS-GUIDED INJECTION OF INTRATUMORAL SUBMICRON PARTICLE PACLITAXEL (SPP) FOR THE TREATMENT OF LOCALLY ADVANCED PANCREATIC ADENOCARCINOMA (LAPC):PHASE 2 STUDY

      Pancreatic cancer is an aggressive malignancy with a 5-year survival rate of 8%. Approximately 30% of all pancreatic tumors present as locally advanced disease (LAPC). Despite recent use of more aggressive chemotherapies and the advances in surgical techniques, the mean survival for most patients with LAPC is approximately 8-13 months. Current chemotherapy agents exhibit systemic toxicities and variable tumor penetrance due to the desmoplastic reaction associated with it. Nanopac is a novel submicron particle paclitaxel (SPP) that can be administered directly into the tumor via EUS. It has no demonstrable systemic distribution and remains in tumor for extended periods of time.

      Aims

      To assess safety and preliminary efficacy of submicron particle paclitaxel (SPP) injected directly into a LAPC lesion via Endoscopic Ultrasound guidance.

      Methods

      Subjects were enrolled to receive EUS-guided intratumoral delivery of an SPP solution of 6, 10, or 15 mg/mL at a volume equivalent to ≤ 20% of the tumor volume, in a standard ‘3+3’ dose-escalation protocol. Following completion of this initial phase, SPP at 15mg/mL is being evaluated in 22 subjects who will receive two equal-dose injections 4 weeks apart. All subjects will be followed for 6 months (m) after initial injection. Tumor responses will be assessed at 3 and 6m post-initial injection using RECIST criteria.

      Results

      Fifteen evaluable subjects have been enrolled to the second phase to date, of whom 7 have completed the study and 2 have passed the 3m assessment. Adverse events include transient mild/moderate abdominal pain, nausea, back pain, bloating, and pancytopenia. Acute pancreatitis has not been reported.
      Evaluation of the tumors has demonstrated stable disease in 8/9 subjects at 3m, and in 6/7 at 6m. One subject had disease progression through 6m. Partial response (>30% difference) at 6m has been demonstrated in 4/6 subjects and 2/6 have stable disease (Table 1;). The 7 evaluable subjects who have completed the study had no new lesions at 6m, and are all surviving (24 - 46 weeks). One subject was down-staged at week 16 and underwent surgical resection (Image).

      Conclusion

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      Image: Scan taken pre- and post-SPP EUS guided injection for subject whose tumor was down staged and was resected, providing negative margins. Lesions went from 2.7 x 2.2cm down to 2.2 x 1.6cm with less involvement of Superior Mesenteric Artery facilitating R0 resection.
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      Table 1RECIST evaluation – Tumor Diameter (largest) and Tumor Volume - in subjects receiving two SPP injections, one month apart.