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

This study has been completed.
Sponsor:
Collaborator:
Information provided by:
Fox Chase Cancer Center
ClinicalTrials.gov Identifier:
NCT00084513
First received: June 10, 2004
Last updated: February 11, 2010
Last verified: February 2010
  Purpose

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 Intervention Phase
Unspecified Adult Solid Tumor, Protocol Specific
Biological: trastuzumab
Drug: imatinib mesylate
Phase 1

Study Type: Interventional
Study Design: 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

Resource links provided by NLM:


Further study details as provided by Fox Chase Cancer Center:

Primary Outcome Measures:
  • Maximum tolerated dose (MTD) of imatinib mesylate given concurrently with trastuzumab (Herceptin®) as measured by CTC v 3.0 at course 1 [ Designated as safety issue: Yes ]
  • Response as measured by RECIST criteria every 9 weeks [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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 [ Designated as safety issue: No ]
  • Phosphorylation status of AKT, extracellular signal-regulated kinase (ERK), and KIT as measured by western blot and/or immunohistochemistry at baseline and week 9 [ Designated as safety issue: No ]

Estimated Enrollment: 18
Study Start Date: August 2004
Study Completion Date: March 2007
Detailed Description:

OBJECTIVES:

Primary

  • 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.

Secondary

  • 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • 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

PATIENT CHARACTERISTICS:

Age

  • 18 and over

Performance status

  • ECOG 0-2

Life expectancy

  • Not specified

Hematopoietic

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

Hepatic

  • 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)

Renal

  • Creatinine ≤ 2.0 mg/dL

Cardiovascular

  • 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

Pulmonary

  • No uncontrolled or significant pulmonary disease

Other

  • 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

PRIOR CONCURRENT THERAPY:

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

Chemotherapy

  • 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

Radiotherapy

  • At least 4 weeks since prior radiotherapy and recovered

Surgery

  • More than 2 weeks since prior major surgery

Other

  • 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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00084513

Locations
United States, Pennsylvania
Fox Chase Cancer Center
Philadelphia, Pennsylvania, United States, 19111-2497
Sponsors and Collaborators
Fox Chase Cancer Center
Investigators
Principal Investigator: Margaret von Mehren, MD Fox Chase Cancer Center
  More Information

Additional Information:
No publications provided

ClinicalTrials.gov Identifier: NCT00084513     History of Changes
Other Study ID Numbers: CDR0000365451, P30CA006927, FCCC-03041, NOVARTIS-FCCC-03041
Study First Received: June 10, 2004
Last Updated: February 11, 2010
Health Authority: United States: Federal Government

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

Additional relevant MeSH terms:
Trastuzumab
Imatinib
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on April 14, 2014