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CC BY-NC-ND 4.0 · Endosc Int Open 2022; 10(12): E1517-E1525
DOI: 10.1055/a-1949-7730
Original article

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

Mohamed Othman
1   Gastroenterology and Hepatology Section, Baylor College of Medicine Medical Center, Houston, Texas, United States
,
Kalpesh Patel
1   Gastroenterology and Hepatology Section, Baylor College of Medicine Medical Center, Houston, Texas, United States
,
Somashekar G. Krishna
2   Division of Gastroenterology, Hepatology and Nutrition, The Ohio State University Wexner Medical Center, Columbus, Ohio, United States
,
Antonio Mendoza-Ladd
3   Division of Gastroenterology, Texas Tech University Health Sciences Center at El Paso, El Paso, Texas, United States
,
Shelagh Verco
4   US Biotest, Inc., San Luis Obispo, California, United States
,
Wasif Abidi
1   Gastroenterology and Hepatology Section, Baylor College of Medicine Medical Center, Houston, Texas, United States
,
James Verco
4   US Biotest, Inc., San Luis Obispo, California, United States
,
Alison Wendt
4   US Biotest, Inc., San Luis Obispo, California, United States
,
Gere diZerega
4   US Biotest, Inc., San Luis Obispo, California, United States
5   NanOlogy, LLC., Fort Worth, Texas, United States
› Author AffiliationsSupported by: NanOlogy, LLC

TRIAL REGISTRATION: Multicenter open-label trial at http://www.clinicaltrials.gov/
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EUS-guided treatments of pancreatic cystic neoplasms – a call for methodological improvementsEndosc Int Open 2022; 10(12): E1526-E1527
DOI: 10.1055/a-1965-3191

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.

Supplementary material



Publication History

Received: 19 April 2022

Accepted after revision: 20 September 2022

Article published online:
15 December 2022

© 2022. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/)

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