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A Randomized Study of Weekly Vinorelbine (Navelbine®) Alone or in Combination With Trastuzumab (Herceptin®) (NSC-688097) for Patients With HER-2-Positive Metastatic Breast Cancer Whose Tumors Have Progressed After Taxane + Trastuzumab Combination Therapy - Phase III


Phase 3
18 Years
N/A
Not Enrolling
Female
Breast Cancer

Thank you

Trial Information

A Randomized Study of Weekly Vinorelbine (Navelbine®) Alone or in Combination With Trastuzumab (Herceptin®) (NSC-688097) for Patients With HER-2-Positive Metastatic Breast Cancer Whose Tumors Have Progressed After Taxane + Trastuzumab Combination Therapy - Phase III


OBJECTIVES:

- Compare progression-free survival (PFS) of women with HER2-positive progressive
metastatic breast cancer treated with vinorelbine with or without trastuzumab
(Herceptin®).

- Compare overall survival and time to treatment failure in patients treated with these
regimens.

- Compare the toxicity of these regimens in these patients.

- Compare the response rate (complete and partial, confirmed and unconfirmed) in patients
with measurable disease treated with these regimens.

- Correlate baseline circulating tumor cells (CTC) with PFS, overall survival, and
disease progression status at 9 weeks in patients treated with these regimens.

- Correlate 4-week CTC with subsequent PFS and overall survival of patients treated with
these regimens.

OUTLINE: This is a randomized, multicenter study. Patients are randomized to 1 of 2
treatment arms.

- Arm I: Patients receive trastuzumab (Herceptin®) IV over 90 minutes and vinorelbine IV
over 10 minutes on day 1 of course 1. Patients receive trastuzumab IV over 30 minutes
and vinorelbine IV over 10 minutes on days 1, 8, 15, and 22 in all subsequent courses.
If trastuzumab is discontinued due to toxicity, patients may continue to receive
vinorelbine alone.

- Arm II: Patients receive vinorelbine IV over 10 minutes on days 1, 8, 15, and 22.

In both arms, courses repeat every 28 days in the absence of disease progression or
unacceptable toxicity.

After completion of study treatment, patients are followed every 3 months until disease
progression and then every 6 months for up to 3 years.

PROJECTED ACCRUAL: A total of 292 patients (146 per treatment arm) will be accrued for this
study within 3 years.

Inclusion Criteria


DISEASE CHARACTERISTICS:

- Histologically confirmed breast cancer

- Clinical evidence of metastatic disease

- HER2-positive tumor, as indicated by one of the following methods:

- HER2 gene amplification by fluorescence in situ hybridization

- HER2 protein overexpression (3+) by immunohistochemistry

- Disease progression during or after prior taxane therapy (single-agent paclitaxel,
docetaxel, or taxane-containing combination chemotherapy) in combination with
trastuzumab (Herceptin®) as first- or second-line chemotherapy for metastatic disease

- Patients who received maintenance therapy with single-agent trastuzumab after
acheiving a response or stable disease to prior taxane/trastuzumab combination
therapy are eligible provided disease has progressed

- Measurable or nonmeasurable disease

- No effusions or ascites as the only sites of disease

- No leptomeningeal disease or lymphatic pulmonary metastases

- Brain metastases allowed provided disease is stable for > 3 months after completion
of prior radiotherapy to the brain

- Hormone receptor status:

- Not specified

PATIENT CHARACTERISTICS:

Age

- 18 and over

Sex

- Female

Menopausal status

- Not specified

Performance status

- Zubrod 0-1

Life expectancy

- Not specified

Hematopoietic

- Absolute neutrophil count ≥ 1,500/mm^3

- Platelet count ≥ 100,000/mm^3

- Hemoglobin ≥ 9 g/dL

Hepatic

- Bilirubin ≤ 2.0 mg/dL

- SGOT or SGPT ≤ 2.5 times upper limit of normal (ULN) (< 5 times ULN in the presence
of liver metastases)

- Alkaline phosphatase ≤ 3 times ULN (< 5 times ULN in the presence of liver or bone
metastases)

Renal

- Creatinine ≤ 2.0 mg/dL

- Calcium ≤ 11.0 mg/dL

Cardiovascular

- No history of significant symptomatic cardiac disease

- LVEF ≥ 50% of the lower limit of normal by MUGA or ECG

Other

- No pre-existing clinically significant (≥ grade 2) motor or sensory neuropathy except
for abnormalities due to cancer

- No other malignancy within the past 5 years except adequately treated basal cell or
squamous cell skin cancer, carcinoma in situ of the cervix, or adequately treated
stage I or II cancer in complete remission

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy

- See Disease Characteristics

- At least 28 days since prior trastuzumab

- No concurrent filgrastim (G-CSF)

Chemotherapy

- See Disease Characteristics

- No more than 2 prior chemotherapy regimens for metastatic breast cancer

- Prior adjuvant/neoadjuvant chemotherapy allowed, for a total of 3 prior regimens

- No prior vinorelbine

- No other prior chemotherapy after progression on a taxane/trastuzumab regimen

- No prior cumulative dose > 360 mg/m^2 of anthracycline-based chemotherapy

Endocrine therapy

- No prior hormonal therapy after progression on a taxane/trastuzumab regimen

- Prior exogenous hormonal therapy for stage IV disease and/or as adjuvant therapy
allowed

Radiotherapy

- See Disease Characteristics

- No prior radiotherapy to > 50% of the marrow-bearing bone

Surgery

- At least 4 weeks since prior major surgery (2 weeks for minor surgery) and recovered

Other

- Concurrent bisphosphonates allowed for bone metastasis

Type of Study:

Interventional

Study Design:

Allocation: Randomized, Primary Purpose: Treatment

Principal Investigator

Lajos Pusztai, MD, MPH, DPhil

Investigator Affiliation:

M.D. Anderson Cancer Center

Authority:

United States: Federal Government

Study ID:

CDR0000409573

NCT ID:

NCT00103233

Start Date:

December 2004

Completion Date:

April 2006

Related Keywords:

  • Breast Cancer
  • stage IV breast cancer
  • recurrent breast cancer
  • Breast Neoplasms

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