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Imatinib Mesylate in Treating Patients With Advanced Cancer and Liver Dysfunction
This study has been completed.
First Received: October 11, 2001   Last Updated: November 16, 2008   History of Changes
Sponsors and Collaborators: UPMC Cancer Centers
National Cancer Institute (NCI)
Information provided by: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00025415
  Purpose

RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die.

PURPOSE: Phase I trial to study the effectiveness of imatinib mesylate in treating patients who have advanced cancer and liver dysfunction.


Condition Intervention Phase
Chronic Myeloproliferative Disorders
Gastrointestinal Stromal Tumor
Leukemia
Lymphoma
Multiple Myeloma and Plasma Cell Neoplasm
Myelodysplastic Syndromes
Myelodysplastic/Myeloproliferative Diseases
Precancerous/Nonmalignant Condition
Small Intestine Cancer
Unspecified Adult Solid Tumor, Protocol Specific
Drug: imatinib mesylate
Phase I

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

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Study Start Date: October 2001
Detailed Description:

OBJECTIVES:

  • Determine the maximum tolerated dose and dose-limiting toxicity of imatinib mesylate in patients with advanced malignancies and varying degrees of liver dysfunction.
  • Determine the effects of hepatic dysfunction on the pharmacodynamics and pharmacokinetics of this drug in these patients.
  • Determine the non-dose-limiting toxic effects of this drug in these patients.
  • Determine the response rate of these patients treated with this drug.
  • 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.

  Eligibility

Ages Eligible for Study:   15 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Histologically or cytologically confirmed surgically incurable solid tumor or hematologic malignancy for which no standard or palliative therapy exists or is 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 be on a stable dose and seizure-free for 1 month
  • No unstable or untreated (non-irradiated) brain metastases

PATIENT CHARACTERISTICS:

Age:

  • Over 15 (Patients 15 -18 years are eligible only if refractory disease and no alternative therapy options exist)

Performance status:

  • ECOG 0-2 OR
  • Karnofsky 60-100%

Life expectancy:

  • More than 3 months

Hematopoietic:

  • 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

Hepatic:

  • See Surgery
  • No evidence of biliary sepsis

Renal:

  • Creatinine normal OR
  • Creatinine clearance at least 60 mL/min

Cardiovascular:

  • No symptomatic congestive heart failure
  • No unstable angina pectoris
  • No cardiac arrhythmia

Other:

  • 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

PRIOR CONCURRENT THERAPY:

Biologic therapy:

  • At least 24 hours since prior colony-stimulating factors
  • No concurrent colony-stimulating factors

Chemotherapy:

  • At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered

Endocrine therapy:

  • See Disease Characteristics

Radiotherapy:

  • See Disease Characteristics
  • At least 4 weeks since prior radiotherapy and recovered

Surgery:

  • 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

Other:

  • 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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00025415

Locations
United States, California
City of Hope Medical Group
Pasadena, California, United States, 91105
UCSF Comprehensive Cancer Center
San Francisco, California, United States, 94115
University of California Davis Cancer Center
Sacramento, California, United States, 95817
USC/Norris Comprehensive Cancer Center and Hospital
Los Angeles, California, United States, 90033
United States, Maryland
Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support
Bethesda, Maryland, United States, 20892-1182
United States, Ohio
Ireland Cancer Center
Cleveland, Ohio, United States, 44106-5065
United States, Pennsylvania
Hillman Cancer Center at University of Pittsburgh Cancer Institute
Pittsburgh, Pennsylvania, United States, 15232
Sponsors and Collaborators
UPMC Cancer Centers
Investigators
Study Chair: Ramesh K. Ramanathan, MD UPMC Cancer Centers
  More Information

Additional Information:
Publications:
Study ID Numbers: CDR0000068959, PCI-01-028, MB-NAVY-B01-053, NCI-02-C-0020, NCI-5331
Study First Received: October 11, 2001
Last Updated: November 16, 2008
ClinicalTrials.gov Identifier: NCT00025415     History of Changes
Health Authority: United States: Federal Government

Keywords provided by National Cancer Institute (NCI):
stage IV adult Hodgkin lymphoma
monoclonal gammopathy of undetermined significance
recurrent adult Hodgkin lymphoma
stage IV cutaneous T-cell non-Hodgkin lymphoma
recurrent cutaneous T-cell non-Hodgkin lymphoma
isolated plasmacytoma of bone
extramedullary plasmacytoma
refractory multiple myeloma
Waldenstrom macroglobulinemia
stage IV chronic lymphocytic leukemia
recurrent adult acute myeloid leukemia
recurrent adult acute lymphoblastic leukemia
relapsing chronic myelogenous leukemia
refractory chronic lymphocytic leukemia
small intestine lymphoma
unspecified adult solid tumor, protocol specific
chronic phase chronic myelogenous leukemia
accelerated phase chronic myelogenous leukemia
blastic phase chronic myelogenous leukemia
meningeal chronic myelogenous leukemia
untreated adult acute lymphoblastic leukemia
untreated adult acute myeloid leukemia
polycythemia vera
chronic idiopathic myelofibrosis
essential thrombocythemia
Philadelphia chromosome positive chronic myelogenous leukemia
untreated hairy cell leukemia
progressive hairy cell leukemia, initial treatment
refractory hairy cell leukemia
chronic myelomonocytic leukemia

Study placed in the following topic categories:
Philadelphia Chromosome
Blast Crisis
Liver Diseases
Mantle Cell Lymphoma
Ileal Diseases
Preleukemia
Leukemia, Prolymphocytic
Hemorrhagic Disorders
Lymphoma, Large-Cell, Anaplastic
Neoplasm Metastasis
Thrombocythemia, Hemorrhagic
Myelodysplastic Myeloproliferative Disease
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Hematologic Diseases
Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative
Leukemia, Myelomonocytic, Chronic
Blood Coagulation Disorders
Leukemia, Myeloid
Imatinib
Waldenstrom Macroglobulinemia
Plasmacytoma
Leukemia, Myeloid, Accelerated Phase
Chronic Myelogenous Leukemia
Lymphoma, Non-Hodgkin
Precancerous Conditions
Blood Protein Disorders
Lymphoma, Follicular
Sezary Syndrome
Lymphoblastic Lymphoma
Lymphoma, B-Cell

Additional relevant MeSH terms:
Liver Diseases
Molecular Mechanisms of Pharmacological Action
Precancerous Conditions
Antineoplastic Agents
Gastrointestinal Diseases
Blood Protein Disorders
Paraproteinemias
Hemostatic Disorders
Protein Kinase Inhibitors
Ileal Diseases
Duodenal Neoplasms
Leukemia
Preleukemia
Neoplasms by Site
Pathologic Processes
Hemorrhagic Disorders
Ileal Neoplasms
Jejunal Diseases
Therapeutic Uses
Syndrome
Cardiovascular Diseases
Lymphoma
Duodenal Diseases
Jejunal Neoplasms
Digestive System Neoplasms
Disease
Neoplasms by Histologic Type
Immunoproliferative Disorders
Immune System Diseases
Hematologic Diseases

ClinicalTrials.gov processed this record on September 02, 2009