Clinical Trial: Imatinib Mesylate in Treating Patients With Advanced Cancer and Liver Dysfunction

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: A Phase I Pharmacokinetic Study of STI571 in Patients With Advanced Malignancies and Varying Levels of Liver Dysfunction

Brief Summary: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Phase I trial to study the effectiveness of imatinib mesylate in treating patients who have advanced cancer and liver dysfunction

Detailed Summary:

PRIMARY OBJECTIVES:

I. Determine the maximum tolerated dose and dose-limiting toxicity of imatinib mesylate in patients with advanced malignancies and varying degrees of liver dysfunction.

II. Determine the effects of hepatic dysfunction on the pharmacodynamics and pharmacokinetics of this drug in these patients.

III. Determine the non-dose-limiting toxic effects of this drug in these patients.

IV. Determine the response rate of these patients treated with this drug. V. Correlate the Childs-Pugh classification of hepatic dysfunction with observed toxic effects, pharmacodynamics, and pharmacokinetics of this drug in these patients.

OUTLINE: This is a dose-escalation, multicenter study. Patients are stratified according to liver dysfunction (normal vs mild vs moderate vs severe).

Patients receive oral imatinib mesylate daily. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients within each stratum (except normal stratum) receive escalating doses of imatinib mesylate 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.

PROJECTED ACCRUAL: A total of 60 patients will be accrued for this study within 1 year.

Sponsor: National Cancer Institute (NCI)

Current Primary Outcome:

• MTD defined based on the toxicities observed during the first cycle of treatment [ Time Frame: 4 weeks ]
• Toxicity evaluation graded according to the NCI common toxicity criteria and relationship to the study drug [ Time Frame: Up to 4 years ]
  Results will be tabulated by liver dysfunction group.

Original Primary Outcome:

Current Secondary Outcome:

• Pharmacokinetic data [ Time Frame: Day 1, 2, 3, 4, 15, 16 ]
  Will be analyzed with ADAPT II, and results will be summarized separately for the four study groups. Additionally, results for pharmacokinetic parameters will be related to the measured level of liver dysfunction in exploratory analyses.
• Responses [ Time Frame: Up to 4 years ]
  Will be tabulated by liver dysfunction group, and by dose if appropriate.
• Child-Pugh Classification [ Time Frame: Baseline ]
  Will be correlated to the toxicities, pharmacokinetic and pharmacodynamic data seen with STI571.

Original Secondary Outcome:

Information By: National Cancer Institute (NCI)

Dates:
Date Received: October 11, 2001
Date Started: August 2001
Date Completion:
Last Updated: February 6, 2013
Last Verified: February 2013