3-AP in Treating Patients With Advanced or Metastatic Solid Tumors
Unspecified Adult Solid Tumor, Protocol Specific
Other: pharmacological study
Procedure: laboratory biomarker analysis
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase I and Pharmacokinetic Study of Oral 3-Aminopyridine-2-Carboxaldehyde Thiosemicarbazone(3-AP,Triapine) in the Treatment of Advanced Solid Tumors|
- Maximum tolerated dose of oral 3-AP determined by dose-limiting toxicities graded according to the NCI CTCAE version 3.0 [ Time Frame: 28 days ] [ Designated as safety issue: Yes ]
- Serum pharmacokinetics of oral triapine [ Time Frame: Baseline, day 4, and day 8 ] [ Designated as safety issue: No ]Summary statistics of the pharmacokinetic parameters will be tabulated using the logarithmic scale where appropriate. The relationship of the AUC to the dose will be assessed by least-square regression analysis.
|Study Start Date:||December 2006|
|Primary Completion Date:||February 2011 (Final data collection date for primary outcome measure)|
Experimental: Arm I
Patients will receive a 2-hour infusion of 3-AP once in week 1. Beginning in week 2, they will receive 3-AP by mouth twice a day 3 days a week for 3 weeks. Treatment with 3-AP by mouth may repeat every 4 weeks for as long as benefit is shown.
Given IV and orally
Other Names:Other: pharmacological study
Other Name: pharmacological studiesProcedure: laboratory biomarker analysis
I. Determine the safety, tolerability, and toxicity of oral 3-AP in patients with advanced solid tumors.
II. Determine the maximum tolerated dose and recommended phase II dose of this drug in these patients.
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00390052
|United States, California|
|City of Hope|
|Duarte, California, United States, 91010|
|Principal Investigator:||Yun Yen||City of Hope Medical Center|