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Imatinib Mesylate in Treating Patients With Advanced Cancer and Kidney Failure
This study has been completed.

First Received on November 9, 2001.   Last Updated on June 9, 2010   History of Changes
Sponsor: Case Comprehensive Cancer Center
Collaborator: National Cancer Institute (NCI)
Information provided by: Case Comprehensive Cancer Center
ClinicalTrials.gov Identifier: NCT00026169
  Purpose

RATIONALE: Imatinib mesylate may stop the growth of cancer cells by stopping the enzyme necessary for cancer cell growth. Kidney failure may delay the elimination of imatinib mesylate from the body, which may lead to longer drug exposure and increase toxic side effects.

PURPOSE: Phase I trial to determine the dose of imatinib mesylate that is most effective with the least amount of toxic side effects in treating patients who have advanced cancer and kidney failure.


Condition Intervention Phase
Brain and Central Nervous System Tumors
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: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I Pharmacokinetic Study Of STI571 In Patients With Advanced Malignancies And Varying Degrees Of Renal Dysfunction For The CTEP-Sponsored Organ Dysfunction Working Group

Resource links provided by NLM:


Further study details as provided by Case Comprehensive Cancer Center:

Primary Outcome Measures:
  • Determine the dose of imatinib mesylate that is most effective with the least amount of toxic side effects. [ Time Frame: Every 28 days in the absence of disease progression or unacceptable toxicity. ] [ Designated as safety issue: Yes ]

Enrollment: 60
Study Start Date: December 2001
Study Completion Date: December 2008
Primary Completion Date: April 2005 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: imatinib mesylate
    Patients receive oral imatinib mesylate once or twice daily on days 1 and 4-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients in each stratum receive escalating doses of imatinib mesylate until the maximum tolerated dose (MTD) is determined.
Detailed Description:

OBJECTIVES:

  • Determine the maximum tolerated dose of imatinib mesylate in patients with advanced malignancies and varying degrees of renal dysfunction.
  • Determine the effects of renal dysfunction on the plasma pharmacokinetics and pharmacodynamics of this drug in these patients.
  • Determine the safety of this drug in these patients.

OUTLINE: This is a dose-escalation study. Patients are stratified according to creatinine clearance (at least 60 mL/min vs 40-59 mL/min vs 20-39 mL/min vs less than 20 mL/min vs any creatinine clearance and undergoing dialysis).

Patients receive oral imatinib mesylate once or twice daily on days 1 and 4-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients in each 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 at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

PROJECTED ACCRUAL: Approximately 60-69 patients (about 12 per stratum) will be accrued for this study.

  Eligibility

Ages Eligible for Study:   16 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Histologically or cytologically confirmed malignancy that is metastatic or unresectable and for which no standard curative therapy exists or palliative measures are no longer effective

    • Hematological malignancies

      • Philadelphia chromosome-positive patients should be enrolled on another NCI or Novartis trial, if possible
    • Myeloproliferative disorders
    • Any solid tumor, and especially:

      • Gastrointestinal stromal tumors
      • Gliomas
  • No untreated (unirradiated) or unstable brain metastases

PATIENT CHARACTERISTICS:

Age:

  • 16 and over

Performance status:

  • ECOG 0-2 OR
  • Karnofsky 60-100%

Life expectancy:

  • At least 3 months

Hematopoietic:

  • WBC at least 3,000/mm^3 OR
  • Absolute neutrophil count at least 1,500/mm^3
  • Platelet count at least 100,000/mm^3

Hepatic:

  • Bilirubin normal
  • AST/ALT no greater than 1.5 times upper limit of normal

Renal:

  • Abnormal kidney function allowed

Cardiovascular:

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

Other:

  • No seizures within the past month (for patients with glioma)
  • No other concurrent uncontrolled illness that would preclude study entry
  • No ongoing or active infection
  • No psychiatric illness or social situation that would preclude study consent
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective barrier contraception during and for 6 months after study participation

PRIOR CONCURRENT THERAPY:

Biologic therapy:

  • Prior immunotherapy allowed
  • No concurrent colony-stimulating factor therapy

Chemotherapy:

  • More than 24 hours since prior hydroxyurea to maintain WBC count in leukemia patients
  • At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin)

Endocrine therapy:

  • Prior hormonal therapy allowed
  • Concurrent corticosteroids must be at a stable dose
  • No concurrent oral contraceptives

Radiotherapy:

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

Surgery:

  • No prior liver, kidney, or lung transplantation
  • At least 14 days since prior major surgery (e.g., thoracotomy or intra-abdominal surgery)

Other:

  • Prior imatinib mesylate allowed
  • No other concurrent investigational agents
  • No concurrent therapeutic doses of warfarin
  • No concurrent tacrolimus or cyclosporine as an immunosuppressive agent
  • No concurrent herbal supplements, vitamins, or other nontraditional compounds
  • No concurrent combination antiretroviral therapy for HIV-positive patients
  • No concurrent acetaminophen of more than 4,000 mg total daily dose
  • Concurrent anticonvulsants must be at a stable dose
  • Concurrent renal dialysis allowed
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00026169

Locations
United States, California
City of Hope Comprehensive Cancer Center
Duarte, California, United States, 91010
USC/Norris Comprehensive Cancer Center and Hospital
Los Angeles, California, United States, 90033-0804
City of Hope National Medical Center / UCI Medical Center
Pasadena, California, United States, 91105
United States, Maryland
Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support
Bethesda, Maryland, United States, 20892-1182
United States, Michigan
Wayne State University
Detroit, Michigan, United States, 48202
United States, New York
Albert Einstein Clinical Cancer Center
Bronx, New York, United States, 10461
NYU School of Medicine's Kaplan Comprehensive Cancer Center
New York, New York, United States, 10016
United States, Ohio
Ireland Cancer Center at University Hospitals Case Medical Center, Case Comprehensive Cancer Center
Cleveland, Ohio, United States, 44106-5065
United States, Pennsylvania
University of Pittsburgh Cancer Institute
Pittsburgh, Pennsylvania, United States, 15213-1863
United States, Texas
University of Texas Health Science Center at San Antonio
San Antonio, Texas, United States, 78229
United States, Wisconsin
University of Wisconsin Comprehensive Cancer Center
Madison, Wisconsin, United States, 53792
Sponsors and Collaborators
Case Comprehensive Cancer Center
Investigators
Study Chair: Afshin Dowlati, MD Ireland Cancer Center at University Hospitals Case Medical Center, Case Comprehensive Cancer Center
  More Information

Additional Information:
Publications:
Responsible Party: Afshin Dowlati, MD, : Ireland Cancer Center at University Hospitals Case Medical Center, Case Comprehensive Cancer Center
ClinicalTrials.gov Identifier: NCT00026169     History of Changes
Obsolete Identifiers: NCT00028392
Other Study ID Numbers: CWRU1Y01, U01CA062502, P30CA043703, CWRU-1Y01, NCI-02-C-0073, NCI-5340
Study First Received: November 9, 2001
Last Updated: June 9, 2010
Health Authority: United States: Federal Government;   United States: Food and Drug Administration

Keywords provided by Case Comprehensive Cancer Center:
recurrent adult brain tumor
adult brain stem glioma
unspecified adult solid tumor, protocol specific
adult anaplastic oligodendroglioma
adult mixed glioma
gastrointestinal stromal tumor
polycythemia vera
Philadelphia chromosome positive chronic myelogenous leukemia
meningeal chronic myelogenous leukemia
blastic phase chronic myelogenous leukemia
relapsing chronic myelogenous leukemia
chronic phase chronic myelogenous leukemia
accelerated phase chronic myelogenous leukemia
AIDS-related peripheral/systemic lymphoma
anaplastic large cell lymphoma
angioimmunoblastic T-cell lymphoma
recurrent adult diffuse large cell lymphoma
recurrent adult diffuse mixed cell lymphoma
recurrent adult diffuse small cleaved cell lymphoma
recurrent adult Burkitt lymphoma
recurrent adult immunoblastic large cell lymphoma
recurrent adult lymphoblastic lymphoma
recurrent cutaneous T-cell non-Hodgkin lymphoma
recurrent grade 1 follicular lymphoma
recurrent grade 2 follicular lymphoma
recurrent grade 3 follicular lymphoma
recurrent mantle cell lymphoma
small intestine lymphoma
stage IV adult diffuse large cell lymphoma
stage IV adult diffuse mixed cell lymphoma

Additional relevant MeSH terms:
Neoplasms
Disease
Leukemia
Lymphoma
Lymphoma, Non-Hodgkin
Multiple Myeloma
Neoplasms, Plasma Cell
Plasmacytoma
Myelodysplastic Syndromes
Preleukemia
Myeloproliferative Disorders
Nervous System Neoplasms
Precancerous Conditions
Lymphoma, Large-Cell, Immunoblastic
Central Nervous System Neoplasms
Duodenal Neoplasms
Ileal Neoplasms
Jejunal Neoplasms
Gastrointestinal Stromal Tumors
Intestinal Neoplasms
Myelodysplastic-Myeloproliferative Diseases
Pathologic Processes
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases

ClinicalTrials.gov processed this record on February 12, 2012