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Cancer Chemotherapy and Pharmacology
Published in: Cancer Chemotherapy and Pharmacology 4/2015

01-10-2015 | Original Article

A first-in-human phase I and pharmacokinetic study of CP-4126 (CO-101), a nucleoside analogue, in patients with advanced solid tumours

Authors: B. Venugopal, A. Awada, T. R. J. Evans, S. Dueland, A. Hendlisz, W. Rasch, K. Hernes, S. Hagen, S. Aamdal

Published in: Cancer Chemotherapy and Pharmacology | Issue 4/2015

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Abstract

Background

CP-4126 (gemcitabine elaidate, previously CO-101) is a lipid–drug conjugate of gemcitabine designed to circumvent human equilibrative nucleoside transporter1-related resistance to gemcitabine. The purpose of this study was to determine the maximum tolerated dose (MTD) and the recommended phase II dose (RP2D) of CP-4126, and to describe its pharmacokinetic profile.

Methods

Eligible patients with advanced refractory solid tumours, and adequate performance status, haematological, renal and hepatic function, were treated with one of escalating doses of CP-4126 administered by a 30-min intravenous infusion on days 1, 8 and 15 of a 28-day cycle. Blood and urine samples were collected to determine the pharmacokinetics (PKs) of CP-4126.

Results

Forty-three patients, median age 59 years (range 18–76; male = 27, female = 16), received one of ten dose levels (30–1600 mg/m2). Dose-limiting toxicities included grade 3 anaemia, grade 3 fatigue and grade 3 elevation of transaminases. The MTD and RP2D were 1250 mg/m2 on basis of the toxicity and PK data. CP-4126 followed dose-dependent kinetics and maximum plasma concentrations occurred at the end of CP-4126 infusion. Seven patients achieved stable disease sustained for ≥3 months, including two patients with pancreatic cancer who had progressed on or after gemcitabine exposure.

Conclusions

CP-4126 was well tolerated with comparable toxicity profile to gemcitabine. Future studies are required to determine its anti-tumour efficacy, either alone or in combination with other cytotoxic chemotherapy regimens.
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Metadata
Title
A first-in-human phase I and pharmacokinetic study of CP-4126 (CO-101), a nucleoside analogue, in patients with advanced solid tumours
Authors
B. Venugopal
A. Awada
T. R. J. Evans
S. Dueland
A. Hendlisz
W. Rasch
K. Hernes
S. Hagen
S. Aamdal
Publication date
01-10-2015
Publisher
Springer Berlin Heidelberg
Published in
Cancer Chemotherapy and Pharmacology / Issue 4/2015
Print ISSN: 0344-5704
Electronic ISSN: 1432-0843
DOI
https://doi.org/10.1007/s00280-015-2846-0

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