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A Phase II Trial of Trastuzumab, Neupogen, and Vinorelbine Investigating the Effects on Immune Function and Clinical Outcomes in Patients With Metastatic Breast Cancer Overexpressing Her-2/Neu

Phase 2/Phase 3
18 Years
Not Enrolling
Metastatic Breast Cancer

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Trial Information

A Phase II Trial of Trastuzumab, Neupogen, and Vinorelbine Investigating the Effects on Immune Function and Clinical Outcomes in Patients With Metastatic Breast Cancer Overexpressing Her-2/Neu

This is a randomized phase II study comparing trastuzumab with G-CSF against trastuzumab
with placebo during the first two weeks of therapy.

Twenty five patients with metastatic breast cancer will be randomized to receive weekly
trastuzumab plus either G-CSF or placebo by subcutaneous (SQ) injection daily for five days
weekly for two weeks. Subsequently, all patients will receive an additional 12 weeks of
weekly trastuzumab, G-CSF by SQ injection daily for five days weekly for 12 weeks, and
vinorelbine once weekly at a dose of 25 mg/m2 weeks 3, 4, 6, 7, 9, 10, 12, 13. Baseline
evaluation will include a history and physical exam, comprehensive metabolic panel (CMP),
complete blood count (CBC), serum pregnancy test, computerized tomography (CT) scan for
disease measurements, and a Multiple Uptake Gated Acquisition (MUGA) scan. The CT scan and
MUGA will be repeated upon completion of the study treatment. Blood will be drawn
pre-trastuzumab, 2 hours post-trastuzumab, and 48 hours post-trastuzumab on weeks 1, 2, 3,
4, and 12 to measure whole blood ADCC activity. Two additional assays for whole blood ADCC
activity will be drawn at baseline pre-treatment, and following completion of protocol
treatment. These assays will measure chromium release from a Her-2 positive target cell
exposed to the patient's effector cells. Measurement of soluble Her-2 in patient serum will
also be measured at each ADCC time point.

Inclusion Criteria:

- All patients must have pathological confirmation of carcinoma of the breast.

- Patients must have metastatic breast cancer by documented clinical or radiological

- Immunohistochemical analysis of HER-2/neu expression on paraffin-embedded specimens
will be performed. HER-2/neu overexpression will be qualitatively scored as 0, 1+,
2+, or 3+, with 3+ indicating the strongest positivity. Fluorescence In Situ
Hybridization (FISH) analyses will also be performed on these patients. Patients
with 2+ to 3+ overexpression of HER-2/neu (membranous staining) are eligible,
regardless of the results of the FISH analysis.

- Age ≥18 years.

- Karnofsky performance status ≥ 60%.

- Adequate hepatic, renal, and hematologic function.

- Prior treatment with trastuzumab will be allowed.

- All patients must have adequate cardiac function (defined as left ventricular
ejection fraction ≥ 45%) documented by echocardiogram or MUGA scan.

- Premenopausal women will be required to have a negative urine or serum pregnancy test
and to use an effective form of contraception.

- Patients with a history of brain metastases are permitted as long as it has been at
least 30 days since definitive treatment, they are clinically stable and a magnetic
resonance imaging scan of the brain demonstrates control of the lesion(s).

- All patients must give written informed consent indicating they are aware of the
investigational nature of this treatment, as well as the risks and benefits of this

Exclusion Criteria:

- No treatment with chemotherapy or trastuzumab will be allowed within four weeks of
study entry.

- Prior therapy with vinorelbine.

- Known history of hypersensitivity to trastuzumab, Chinese hamster ovary (CHO) cell
proteins, or any component of these products.

- History of current unstable angina, symptomatic congestive heart failure, or
myocardial infarction within the last 6 months.

- Pregnant women are excluded.

- History of a known hypersensitivity to E. coli-derived proteins, filgrastim, or any
component of the product.

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Outcome Measure:

To compare antibody dependent cell-mediated cytotoxicity of effector cells isolated from subjects receiving trastuzumab with either G-CSF or a saline placebo against a Her-2 overexpressing target in vitro

Outcome Time Frame:

Two weeks

Safety Issue:


Principal Investigator

Gary N Schwartz, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Norris Cotton Cancer Center


United States: Institutional Review Board

Study ID:




Start Date:

July 2002

Completion Date:

March 2009

Related Keywords:

  • Metastatic Breast Cancer
  • Breast cancer
  • Her-2/neu
  • Granulocyte Colony Stimulating Factor
  • Trastuzumab
  • Vinorelbine
  • Antibody-dependent cellular cytotoxicity
  • Effector cells
  • Breast Neoplasms