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Published in: Cancer Chemotherapy and Pharmacology 1/2024

Open Access 22-09-2023 | Solid Tumor | Original Article

A phase I study of the ceramide nanoliposome in patients with advanced solid tumors

Authors: Aaron Ciner, Theodore Gourdin, Jeff Davidson, Mylisa Parette, Susan J. Walker, Todd E. Fox, Yixing Jiang

Published in: Cancer Chemotherapy and Pharmacology | Issue 1/2024

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Abstract

Purpose

Ceramide is a sphingolipid metabolite that deactivates multiple oncogenic signaling pathways and promotes cell death. In-vivo data demonstrate single-agent anti-cancer activity and enhanced efficacy with combination strategies. This phase I dose-escalation trial evaluated Ceramide nanoLiposomes (CNL) in patients with advanced solid tumors and no standard treatment option.

Methods

The primary objective was to establish the maximum tolerated dose. Secondary objectives included determining the recommended phase II dose, the safety and tolerability, the pharmacokinetic profile and preliminary anti-tumor efficacy.

Results

15 patients with heavily pretreated metastatic disease enrolled. Safety data were analyzed for all patients, while pharmacokinetic data were available for 14 patients. There were no grade 3 or higher treatment-related adverse events. The maximum tolerated dose was not reached and there were no dose-limiting toxicities. The most common grade 1 or 2 treatment-related adverse events included headache, fatigue, constipation, nausea and transaminitis. The maximum concentration and area under the curve increased with dose. Clearance was consistent between doses and was observed mainly through the liver without significant hepatotoxicity. The half-life ranged from 20 to 30 h and the volume of distribution was consistent with a lipophilic drug.

Conclusions

CNL exhibited an encouraging safety profile and pharmacokinetic parameters, with some signals of efficacy including prolonged stable disease in 1 patient with refractory pancreatic cancer. Pre-clinical data indicate potential synergy between CNL and multiple systemic therapies including chemotherapy, targeted therapy, and immunotherapy. Future studies are planned investigating CNL in combination strategies.

Trial registration

This study is registered under ClinicalTrials.gov ID: NCT02834611.
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Metadata
Title
A phase I study of the ceramide nanoliposome in patients with advanced solid tumors
Authors
Aaron Ciner
Theodore Gourdin
Jeff Davidson
Mylisa Parette
Susan J. Walker
Todd E. Fox
Yixing Jiang
Publication date
22-09-2023
Publisher
Springer Berlin Heidelberg
Keyword
Solid Tumor
Published in
Cancer Chemotherapy and Pharmacology / Issue 1/2024
Print ISSN: 0344-5704
Electronic ISSN: 1432-0843
DOI
https://doi.org/10.1007/s00280-023-04588-7

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