Imatinib Mesylate in Treating Patients With Advanced Cancer and Liver Dysfunction

February 6, 2013 updated by: National Cancer Institute (NCI)

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

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

Study Overview

Status

Completed

Conditions

Detailed Description

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.

Study Type

Interventional

Enrollment (Actual)

60

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • Pennsylvania
      • Pittsburgh, Pennsylvania, United States, 15232
        • University of Pittsburgh

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

15 years and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Histologically or cytologically confirmed surgically incurable solid tumor orhematologic malignancy for which no standard or palliative therapy exists oris no longer effective

    • All tumor types are eligible, including:

      • Chronic myelogenous leukemia or other Philadelphia chromosome-positive leukemia OR
      • Gastrointestinal stromal tumors
  • Patients with gliomas that require corticosteroids or anticonvulsants must beon a stable dose and seizure-free for 1 month
  • No unstable or untreated (non-irradiated) brain metastases
  • Performance status - ECOG 0-2
  • Performance status - Karnofsky 60-100%
  • More than 3 months
  • WBC at least 3,000/mm^3
  • Absolute neutrophil count at least 1,500/mm^3
  • Platelet count at least 100,000/mm^3
  • No active hemolysis
  • See Surgery
  • No evidence of biliary sepsis
  • Creatinine normal
  • Creatinine clearance at least 60 mL/min
  • No symptomatic congestive heart failure
  • No unstable angina pectoris
  • No cardiac arrhythmia
  • Able to swallow pills
  • No other uncontrolled concurrent illness that would preclude study participation
  • No ongoing or active infection
  • No uncontrolled diarrhea
  • No psychiatric illness or social situation that would preclude study compliance
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective barrier contraception during and for 6 months after study completion
  • At least 24 hours since prior colony-stimulating factors
  • No concurrent colony-stimulating factors
  • At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered
  • See Disease Characteristics
  • See Disease Characteristics
  • At least 4 weeks since prior radiotherapy and recovered
  • See Disease Characteristics
  • At least 10 days since prior placement of shunt for treatment of biliary obstruction
  • At least 14 days since prior major surgery
  • No prior solid organ transplantation
  • No other concurrent investigational agents
  • No concurrent therapeutic doses of warfarin for anticoagulation
  • No other concurrent investigational or commercial agents or therapies for treatment of this disease
  • No concurrent combination antiretroviral therapy for HIV-positive patients
  • No concurrent acetaminophen of more than 4,000 mg/day

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Treatment (imatinib mesylate)
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
Correlative studies
Other Names:
  • pharmacological studies
Given orally
Other Names:
  • Gleevec
  • CGP 57148
  • Glivec

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
MTD defined based on the toxicities observed during the first cycle of treatment
Time Frame: 4 weeks
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.
Up to 4 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Day 1, 2, 3, 4, 15, 16
Responses
Time Frame: Up to 4 years
Will be tabulated by liver dysfunction group, and by dose if appropriate.
Up to 4 years
Child-Pugh Classification
Time Frame: Baseline
Will be correlated to the toxicities, pharmacokinetic and pharmacodynamic data seen with STI571.
Baseline

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Principal Investigator: Ramesh Ramanathan, University of Pittsburgh

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

August 1, 2001

Primary Completion (Actual)

January 1, 2005

Study Registration Dates

First Submitted

October 11, 2001

First Submitted That Met QC Criteria

January 26, 2003

First Posted (Estimate)

January 27, 2003

Study Record Updates

Last Update Posted (Estimate)

February 7, 2013

Last Update Submitted That Met QC Criteria

February 6, 2013

Last Verified

February 1, 2013

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NCI-2012-02418
  • U01CA099168 (U.S. NIH Grant/Contract)
  • U01CA062502 (U.S. NIH Grant/Contract)
  • U01CA062505 (U.S. NIH Grant/Contract)
  • U01CA062491 (U.S. NIH Grant/Contract)
  • U01CA062487 (U.S. NIH Grant/Contract)
  • 01-028
  • CDR0000068959 (Registry Identifier: PDQ (Physician Data Query))

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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