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

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ClinicalTrials.gov 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

Brief Summary:

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.

Condition or disease Intervention/treatment Phase
Unspecified Adult Solid Tumor, Protocol Specific Biological: trastuzumab Drug: imatinib mesylate Phase 1

Detailed Description:



  • 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.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 18 participants
Primary Purpose: Treatment
Official Title: Phase I of Trastuzumab and Imatinib Mesylate (Gleevec®, Formerly Known as STI-571) in Patients With Recurrent or Metastatic Her-2/Neu Expressing Cancer
Study Start Date : August 2004
Study Completion Date : March 2007

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Primary Outcome Measures :
  1. Maximum tolerated dose (MTD) of imatinib mesylate given concurrently with trastuzumab (Herceptin®) as measured by CTC v 3.0 at course 1
  2. Response as measured by RECIST criteria every 9 weeks

Secondary Outcome Measures :
  1. 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
  2. Phosphorylation status of AKT, extracellular signal-regulated kinase (ERK), and KIT as measured by western blot and/or immunohistochemistry at baseline and week 9

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No


  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00084513

United States, Pennsylvania
Fox Chase Cancer Center
Philadelphia, Pennsylvania, United States, 19111-2497
Sponsors and Collaborators
Fox Chase Cancer Center
National Cancer Institute (NCI)
Principal Investigator: Margaret von Mehren, MD Fox Chase Cancer Center

ClinicalTrials.gov Identifier: NCT00084513     History of Changes
Other Study ID Numbers: CDR0000365451
P30CA006927 ( U.S. NIH Grant/Contract )
First Posted: June 11, 2004    Key Record Dates
Last Update Posted: February 12, 2010
Last Verified: February 2010

Keywords provided by Fox Chase Cancer Center:
unspecified adult solid tumor, protocol specific

Additional relevant MeSH terms:
Imatinib Mesylate
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action