A Phase I Study of AT7519M Given Twice Weekly in Patients With Advanced Incurable Malignancy
- Determine the recommended phase II dose of AT7519M in patients with advanced or
metastatic solid tumors or refractory non-Hodgkin's lymphoma.
- Determine the safety, tolerability, toxicity profile, and dose-limiting toxicities of
this drug in these patients.
- Determine the pharmacokinetic profile of this drug in these patients.
- Correlate the toxicity profile with pharmacokinetics of this drug in these patients.
- Assess, preliminarily, the antitumor activity of this drug in these patients.
OUTLINE: This is an open-label, dose-escalation, multicenter study.
Patients receive AT7519M IV over 1-3 hours on days 1, 4, 8, and 11. Courses repeat every 21
days in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of AT7519M 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 during course 1. Once the MTD has been
determined, up to 8 additional patients are treated at the MTD.
Patients undergo blood collection periodically for pharmacokinetic studies. Patients treated
at the MTD also undergo tumor tissue biopsies or aspirates and blood collection periodically
for additional pharmacodynamic and correlative biomarker studies.
After completion of study therapy, patients are followed at 4 weeks. Patients with complete
response, partial response, or stable disease are followed every 3 months thereafter until
PROJECTED ACCRUAL: A total of 30 patients will be accrued for this study.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Maximum tolerated dose as assessed by NCI CTCAE v.30
from time of 1st dose
Sebastien Hotte, MD
Margaret and Charles Juravinski Cancer Centre
Canada: Health Canada