Investigational New Drugs

, Volume 23, Issue 5, pp 445–453

A phase I study of T900607 given once every 3 weeks in patients with advanced refractory cancers; National Cancer Institute of Canada Clinical Trials Group (NCIC–CTG) IND 130

  • Karen A. Gelmon
  • Karl Belanger
  • Denis Soulieres
  • Carolyn Britten
  • Stephen Chia
  • Danielle Charpentier
  • Kim Chi
  • Jean Powers
  • Wendy Walsh
  • Lesley Seymour
Article

DOI: 10.1007/s10637-005-2904-2

Cite this article as:
Gelmon, K.A., Belanger, K., Soulieres, D. et al. Invest New Drugs (2005) 23: 445. doi:10.1007/s10637-005-2904-2

Abstract

Background: T900607 is a novel tubulin active agent which disrupts microtubule polymerization by a unique mechanism of action. This phase I trial was conducted to determine the maximum tolerated dose, recommended phase II dose, pharmacokinetic properties and toxicities of this agent. Patients and methods: Patients with advanced and/or metastatic solid malignancies were enrolled, for an open dose escalation of T900607 administered intravenously over 30 minutes every 21-days. Results: Thirty patients were enrolled on 7 dose levels ranging from 15 to 270 mg/m2. No DLTs were seen until 270 mg/m2, the sixth dose level, with 1 patient experiencing Grade 3 thrombocytopenia, 1 grade 4 troponin increase and 1 grade 5 myocardial infarction in an expanded cohort of 6 patients. The dose was decreased to 180 mg/m2 with increased cardiac monitoring and at this dose 3/4 patients experienced cardiac toxicity. Further animal cardiotoxicity studies failed to reveal any cardiac effects and the study was reopened at 130 mg/m2; of 6 enrolled patients, 1 had grade 3 drug related lethargy considered to be a DLT and this dose was considered the RP2D. No objective responses were seen but stable disease was reported in 7/20. Pharmacokinetic analysis showed that AUC and Cmax increased with dose with considerable intrapatient variability, a short half life of < 1 hour, and no apparent dose dependency clearance. Conclusions: The recommended phase II dose for T900607 is 130 mg/m2 given as an intravenous infusion over 60 minutes on a 21-day cycle. Cardiac toxicity was seen with this schedule.

Keywords

phase I tubulin active agent 

Copyright information

© Springer Science + Business Media, Inc. 2005

Authors and Affiliations

  • Karen A. Gelmon
    • 1
    • 4
  • Karl Belanger
    • 2
  • Denis Soulieres
    • 2
  • Carolyn Britten
    • 1
  • Stephen Chia
    • 1
  • Danielle Charpentier
    • 2
  • Kim Chi
    • 1
  • Jean Powers
    • 3
  • Wendy Walsh
    • 3
  • Lesley Seymour
    • 3
  1. 1.British Columbia Cancer AgencyVancouver Cancer CentreVancouverCanada
  2. 2.CHUM—Pavillon Notre DameMontreal
  3. 3.NCIC Clinical Trials GroupKingstonCanada
  4. 4.British Columbia Cancer AgencyVancouver Cancer CentreVancouverCanada