A Phase I Study of AEG35156 in Combination With Docetaxel in Patients With Solid Tumors
- Determine the maximum tolerated dose and define the recommended phase II dose of
AEG35156 in combination with docetaxel in patients with solid tumors.
- Determine the qualitative and quantitative toxicities of AEG35156 and docetaxel and
define duration and reversibility of those toxicities.
- Determine the pharmacokinetic profile of this regimen.
- Assess, preliminarily, the antitumor activity of this regimen in patients with
- Assess the pharmacodynamic effects of AEG35156 administration on X-linked inhibitor of
apoptosis protein (XIAP) levels and apoptosis in peripheral blood mononuclear cells
and, in selected patients, in tumor tissue.
- Evaluate M30/M65 cytokeratin 18 level, a marker of apoptosis/necrosis of epithelial
tumors, in these patients.
OUTLINE: This is a multicenter, open-label, dose-escalation study of AEG35156.
Patients receive AEG35156 IV continuously on days -2 and -1. Patients then receive AEG35156
IV continuously over 24 hours on days 1, 8, and 15. Beginning with course 2, patients also
receive docetaxel IV over 1 hour on day 1. Treatment repeats every 3 weeks for up to 6
courses in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of AEG35156 until the maximum tolerated
dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2
of 6 patients experience dose-limiting toxicity.
Blood is collected at baseline and periodically during study treatment for pharmacokinetic
and pharmacodynamic assessment.
After completion of study treatment, patients are followed at 4 weeks and then every 3
PROJECTED ACCRUAL: A total of 30 patients will be accrued for this study.
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Safety and toxicity evaluated according to the NCI CTCAE version 3.0
Every 3 weeks
Gerald Batist, MD
Jewish General Hospital
Canada: Health Canada