Vinorelbine With or Without Trastuzumab in Treating Women With Progressive Metastatic Breast Cancer

This study has been completed.
Sponsor:
Collaborator:
Information provided by:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00103233
First received: February 7, 2005
Last updated: June 21, 2013
Last verified: August 2005
  Purpose

RATIONALE: Drugs used in chemotherapy, such as vinorelbine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as trastuzumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Trastuzumab may also help vinorelbine work better by making tumor cells more sensitive to the drug. Giving vinorelbine together with trastuzumab may be an effective treatment for breast cancer. It is not yet known whether giving vinorelbine together with trastuzumab is more effective than vinorelbine alone in treating breast cancer.

PURPOSE: This randomized phase III trial is studying vinorelbine and trastuzumab to see how well they work compared to vinorelbine alone in treating women with progressive metastatic breast cancer.


Condition Intervention Phase
Breast Cancer
Biological: trastuzumab
Drug: vinorelbine tartrate
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Study Start Date: December 2004
Study Completion Date: April 2006
Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00103233

Sponsors and Collaborators
Southwest Oncology Group
Investigators
Investigator: Lajos Pusztai, MD, MPH, DPhil M.D. Anderson Cancer Center
Investigator: Francisco J. Esteva, MD M.D. Anderson Cancer Center
  More Information

Additional Information:
No publications provided

ClinicalTrials.gov Identifier: NCT00103233     History of Changes
Other Study ID Numbers: CDR0000409573, SWOG-S0347
Study First Received: February 7, 2005
Last Updated: June 21, 2013
Health Authority: United States: Federal Government

Keywords provided by National Cancer Institute (NCI):
stage IV breast cancer
recurrent breast cancer

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Trastuzumab
Vinorelbine
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Antineoplastic Agents, Phytogenic

ClinicalTrials.gov processed this record on September 18, 2014