Trastuzumab and Imatinib Mesylate in Treating Patients With Recurrent or Metastatic HER2/Neu-Expressing Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00084513
Recruitment Status : Completed
First Posted : June 11, 2004
Last Update Posted : February 12, 2010
National Cancer Institute (NCI)
Information provided by:
Fox Chase Cancer Center

June 10, 2004
June 11, 2004
February 12, 2010
August 2004
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  • Maximum tolerated dose (MTD) of imatinib mesylate given concurrently with trastuzumab (Herceptin®) as measured by CTC v 3.0 at course 1
  • Response as measured by RECIST criteria every 9 weeks
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Complete list of historical versions of study NCT00084513 on Archive Site
  • Circulating tumor cells in blood as measured by Immunicom Cell PrepTM at baseline, every 3 weeks until week 9, and then with each disease re-evaluation
  • Phosphorylation status of AKT, extracellular signal-regulated kinase (ERK), and KIT as measured by western blot and/or immunohistochemistry at baseline and week 9
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Trastuzumab and Imatinib Mesylate in Treating Patients With Recurrent or Metastatic HER2/Neu-Expressing Cancer
Phase I of Trastuzumab and Imatinib Mesylate (Gleevec®, Formerly Known as STI-571) in Patients With Recurrent or Metastatic Her-2/Neu Expressing Cancer

RATIONALE: Monoclonal antibodies such as trastuzumab can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. Imatinib mesylate may stop the growth of tumor cells by blocking the enzymes necessary for their growth and by stopping blood flow to the tumor. Giving trastuzumab together with imatinib mesylate may kill more tumor cells.

PURPOSE: This phase I trial is studying the side effects and best dose of imatinib mesylate when given together with trastuzumab in treating patients with recurrent or metastatic HER2/neu-expressing (producing) cancer.



  • Determine the maximum tolerated dose of imatinib mesylate when administered with trastuzumab (Herceptin®) in patients with recurrent or metastatic HER2/neu-overexpressing cancer.
  • Determine response in patients treated with this regimen.


  • Correlate the number of circulating tumor cells with radiographic imaging in patients treated with this regimen.

OUTLINE: This is a dose-escalation study of imatinib mesylate.

Patients receive trastuzumab (Herceptin®) IV over 90 minutes on day 1 and oral imatinib mesylate once or twice daily on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients 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: Approximately 9-18 patients will be accrued for this study.

Phase 1
Primary Purpose: Treatment
Unspecified Adult Solid Tumor, Protocol Specific
  • Biological: trastuzumab
  • Drug: imatinib mesylate
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*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
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March 2007
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  • Histologically or cytologically confirmed cancer that overexpresses HER2/neu, measured 3+ by immunohistochemistry or positive by fluorescence in situ hybridization

    • Recurrent or metastatic disease
  • Meets 1 of the following criteria for measurable or evaluable disease:

    • Unidimensionally measurable disease at least 20 mm by conventional techniques OR at least 10 mm by spiral CT scan
    • Evaluable disease, defined as a lesion on physical examination or imaging study that can be assessed as to changes in size but cannot be clearly measured in 1 dimension (e.g., pleural effusions, ascites, or bone disease)
  • No carcinomatous meningitis or untreated/uncontrolled metastatic brain parenchymal disease

    • Prior controlled brain parenchymal disease allowed provided at least 8 weeks since prior therapy AND no symptomatic progression off corticosteroids



  • 18 and over

Performance status

  • ECOG 0-2

Life expectancy

  • Not specified


  • Absolute neutrophil count ≥ 1,500/mm^3
  • Platelet count ≥ 100,000/mm^3


  • ALT and AST ≤ 2.0 times upper limit of normal (ULN)
  • Alkaline phosphatase ≤ 2.0 times ULN
  • Bilirubin ≤ 1.3 mg/dL
  • No known chronic liver disease (i.e., chronic active hepatitis or cirrhosis)


  • Creatinine ≤ 2.0 mg/dL


  • Ejection fraction ≥ lower limit of normal by MUGA
  • No uncontrolled or significant cardiovascular disease
  • No myocardial infarction within the past 6 months
  • No ischemic heart disease requiring medication
  • No congestive heart failure


  • No uncontrolled or significant pulmonary disease


  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective barrier contraception during and for 3 months after study participation
  • No active unresolved infection


Biologic therapy

  • Prior trastuzumab (Herceptin®) allowed
  • No concurrent filgrastim (G-CSF) or sargramostim (GM-CSF) to support blood counts
  • No other concurrent anticancer biologic agents


  • Prior chemotherapy for metastatic disease allowed
  • At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas) and recovered
  • No concurrent anticancer chemotherapy

Endocrine therapy

  • See Disease Characteristics


  • At least 4 weeks since prior radiotherapy and recovered


  • More than 2 weeks since prior major surgery


  • At least 7 days since prior antibiotics
  • No concurrent parenteral antibiotics
  • No other concurrent anticancer agents
  • No other concurrent investigational drugs
  • No concurrent therapeutic anticoagulation with warfarin

    • Concurrent mini-dose warfarin (1 mg/day) for prophylaxis of central venous catheter thrombosis allowed
Sexes Eligible for Study: All
18 Years and older   (Adult, Older Adult)
Contact information is only displayed when the study is recruiting subjects
United States
P30CA006927 ( U.S. NIH Grant/Contract )
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Fox Chase Cancer Center
National Cancer Institute (NCI)
Principal Investigator: Margaret von Mehren, MD Fox Chase Cancer Center
Fox Chase Cancer Center
February 2010

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP