A Phase I and Pharmacokinetic Study of Oral 3-Aminopyridine-2-Carboxaldehyde Thiosemicarbazone(3-AP,Triapine) in the Treatment of Advanced Solid Tumors
I. Determine the safety, tolerability, and toxicity of oral 3-AP in patients with advanced
II. Determine the maximum tolerated dose and recommended phase II dose of this drug in these
III. Determine the oral bioavailability and pharmacokinetics of this drug. IV. Assess
tumoral expression of genes involved in response and resistance to 3-AP.
V. Observe and record any tumor response in these patients.
OUTLINE: This is a multicenter, dose-escalation study.
Patients receive a one time dose of 3-AP IV over 2 hours on day -7. Patients then receive
oral 3-AP twice daily on days 1-3, 8-10, and 15-17. Treatment repeats every 28 days in the
absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive
escalating doses of oral 3-AP 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 samples for pharmacokinetic analysis are collected
periodically over 8 hours after the IV dose of 3-AP and after the first oral dose of 3-AP
during course 1.
After completion of study treatment, patients are followed periodically.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Maximum tolerated dose of oral 3-AP determined by dose-limiting toxicities graded according to the NCI CTCAE version 3.0
City of Hope Medical Center
United States: Food and Drug Administration
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