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. 2022 Dec 15;10(12):E1517-E1525.
doi: 10.1055/a-1949-7730. eCollection 2022 Dec.

Early phase trial of intracystic injection of large surface area microparticle paclitaxel for treatment of mucinous pancreatic cysts

Mohamed Othman  1 , Kalpesh Patel  1 , Somashekar G Krishna  2 , Antonio Mendoza-Ladd  3 , Shelagh Verco  4 , Wasif Abidi  1 , James Verco  4 , Alison Wendt  4 , Gere diZerega  4   5
Affiliations

Early phase trial of intracystic injection of large surface area microparticle paclitaxel for treatment of mucinous pancreatic cysts

Mohamed Othman et al. Endosc Int Open. .

Abstract

Background and study aims Mucinous pancreatic cystic lesions (PCLs) have the potential for malignant transformation, for which the only accepted curative modality is surgery. A novel intracystic therapy with large surface area microparticle paclitaxel (LSAM-PTX) may treat PCLs without local or systemic toxicities. Safety and preliminary efficacy of LSAM-PTX for the treatment of PCLs administered by endoscopic ultrasound-guided fine-needle injection (EUS-FNI) was evaluated. Patients and methods Ten subjects with confirmed PCLs (size > 1.5 cm) received intracystic LSAM-PTX via EUS-FNI at volumes equal to those aspirated from the cyst in sequential cohorts at 6, 10, and 15 mg/mL in a standard "3 + 3" dose-escalation protocol. The highest dose with acceptable safety and tolerability was taken into the confirmatory phase where nine additional subjects received two injections of LSAM-PTX 12 weeks apart. Subjects were followed for 6 months after initial LSAM-PTX treatment for endpoints including: adverse events (AEs), tolerability, pharmacokinetic analysis of systemic paclitaxel drug levels, and change in cyst volume. Results Nineteen subjects completed the study. No dose-limiting toxicities, treatment-related serious AEs, or clinically significant laboratory changes were reported. Systemic paclitaxel concentrations did not exceed 3.5 ng/mL at any timepoint measured and fell below 1 ng/mL by Week 2, supporting the lack of systemic toxicity. By Week 24 a cyst volume reduction (10-78 %) was seen in 70.6 % of subjects. Conclusions Intracystic injection of LSAM-PTX into mucinous PCLs resulted in no significant AEs, a lack of systemic absorption, and resulted in reduction of cyst volume over a 6 month period.

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Conflict of interest statement

Competing interests Gere diZerega holds a consultant/advisory role, has stock ownership or receives funding from NanOlogy, LLC. Shelagh Verco, James Verco, and Alison Wendt are full-time employees of NanOlogy, LLC. Mohamed O Othman is a consultant for Abbvie, BSC, Olympus, Conmed, Apollo and Nestle and received grant funding from Abbvie, Lucid Diagnostics, Conmed and NanOlogy, LLC. Kalpesh Patel is a consultant for Conmed and Abbvie. Somashekar G. Krishna is PI of an investigator-initiated study in part funded by a grant to The Ohio State University Wexner Medical Center from Mauna Kea Technologies, Paris, France. The remaining authors declare that they have no conflict of interest.

Figures

Fig. 1
Fig. 1
Flow diagram for subjects enrolled to receive large surface area microparticle paclitaxel (LSAM-PTX).
Fig. 2
Fig. 2
Change in cyst volume based on single or two injections of large surface area microparticle paclitaxel (LSAM-PTX) at Week 12 and 24. 1 Subject was enrolled in the two-injection group but received a single injection. 2 Subject did not have a Week 12 CT scan. 3 Subject did not have a Week 24 CT scan.
See this image and copyright information in PMC

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