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Developmental therapeutics

1384 - An open-label, randomized cross-over bioavailability study of oral paclitaxel and HM30181 compared with weekly intravenous (IV) paclitaxel in patients with advanced solid tumours (133O)

Date

18 Nov 2017

Session

Developmental therapeutics

Presenters

Christopher Jackson

Citation

Annals of Oncology (2017) 28 (suppl_10): x39-x41. 10.1093/annonc/mdx658

Authors

C.G.C.A. Jackson1, S. Deva2, K. Bayston3, P. Barlow2, K. Eden4, N. Hung5, G. Fetterly6, D. Cutler6, R. Kwan6, D. Kramer6, W. Chan6, T. Hung7

Author affiliations

  • 1 Department Of Medicine, University of Otago, 9016 - Dunedin/NZ
  • 2 Regional Cancer And Blood Service, Auckland District Health Board, Auckland/NZ
  • 3 Southern Blood And Cancer, Southern District Health Board, Invercargill/NZ
  • 4 Southern Blood And Cancer, Southern District Health Board, 9016 - Dunedin/NZ
  • 5 Department Of Pathology, University of Otago, 9016 - Dunedin/NZ
  • 6 -, Athenex, Buffalo/US
  • 7 -, Zenith Technologies, Dunedin/NZ
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Abstract 1384

Background

Paclitaxel has poor oral bioavailability due to active excretion by p-glycoprotein (Pgp) on intestinal epithelial cells. Oral administration is preferable to IV administration to minimize IV access, avoid allergic reactions to cremaphor, obviate steroid pre-medication, reduce day stay, provide cost-savings, and improve patient convenience. Oraxol (Athenex, USA) is a combination of oral paclitaxel and HM30181, a novel oral non-absorbed specific inhibitor of intestinal Pgp. Following a previously reported phase 1 dose-escalation study, we report the preliminary bio-equivalence results of a three-day schedule of Oraxol compared to IV paclitaxel.

Methods

We conducted a randomized crossover study recruiting patients from 2 sites in New Zealand. HM30181 15mg plus oral paclitaxel 205mg/m2 (®Oraxol) were administered orally once daily for 3 consecutive days and compared to a single dose of IV paclitaxel (80 mg/m2) in patients with advanced solid tumours. PK blood samples were taken up to day 9 for Oraxol and day 5 for IV paclitaxel.

Results

A scheduled interim analysis of the first 6 patents’ Oraxol PK (AUC0-∞) compared to IV paclitaxel showed: - Geometric mean ratios (GMR) = 87.09%, (90% CI 74.61-101.66%) - Intra-subject coefficients of variation (CV) = 12.62% - Time over minimum effective concentration was approximately 6 hours for IV paclitaxel, and 30 hours for Oraxol. Further results will be presented. The safety profile of Oraxol was acceptable without grade 3-4 toxicities. A total sample size of 30 subjects is required to demonstrate bioequivalence between Oraxol and IV paclitaxel (90% CI of the GMR is within the limits of 80% – 125%), with 80% power.

Conclusions

Oraxol 615mg/m2 orally over three days achieved paclitaxel AUC comparable to IV paclitaxel 80mg/m2. A three-day schedule of Oraxol is within predicted range needed to demonstrate bioequivalence, and further patients are being enrolled to achieve adequate power. A phase 3 study is now underway.

Clinical trial indentification

ACTRN 12615000894594.

Clinical trial identification

ACTRN 12615000894594.

Legal entity responsible for the study

Athenex

Funding

Athenex

Disclosure

G. Fetterly, R. Kwan, W-K. Chan: Employee of Athenex, D. Cutler: Employee and shareholder in Athenex, D. Kramer: Employee of Athenex; Shareholder in Athenex, All other authors have declared no conflicts of interest.

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