Capecitabine, Vinorelbine, and Trastuzumab in Treating Patients With Metastatic Breast Cancer

This study has been completed.
Sponsor:
Collaborator:
Information provided by:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00093808
First received: October 6, 2004
Last updated: June 17, 2012
Last verified: January 2009
  Purpose

RATIONALE: Drugs used in chemotherapy, such as capecitabine and vinorelbine, work in different ways to stop tumor cells from dividing so they stop growing or die. Monoclonal antibodies such as trastuzumab can locate tumor cells and either kill them or deliver tumor killing substances to them without harming normal cells. Giving capecitabine and vinorelbine together with trastuzumab may kill more tumor cells.

PURPOSE: This phase II trial is studying how well giving capecitabine and vinorelbine together with trastuzumab works in treating patients who have metastatic breast cancer.


Condition Intervention Phase
Breast Cancer
Biological: trastuzumab
Drug: capecitabine
Drug: vinorelbine tartrate
Phase 2

Study Type: Interventional
Study Design: Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Study of Capecitabine in Combination With Vinorelbine and Trastuzumab for the First- or Second-LineTreatment of HER2+ Metastatic Breast Cancer

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Overall response rate as measured by RECIST criteria [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Time to progression as measured by RECIST criteria [ Designated as safety issue: No ]
  • Duration of response as measured by RECIST criteria [ Designated as safety issue: No ]
  • Overall survival as assessed by time [ Designated as safety issue: No ]
  • Safety as assessed by CTC3 [ Designated as safety issue: Yes ]

Estimated Enrollment: 47
Study Start Date: August 2004
Primary Completion Date: December 2008 (Final data collection date for primary outcome measure)
Detailed Description:

OBJECTIVES:

Primary

  • Determine the overall response rate in patients with HER2/neu-overexpressing metastatic breast cancer treated with first- or second-line therapy comprising capecitabine, vinorelbine, and trastuzumab (Herceptin^®).

Secondary

  • Determine the time to disease progression, duration of response, and overall survival of patients treated with this regimen.
  • Determine the safety profile of this regimen in these patients.

OUTLINE: This is a multicenter study.

Patients receive oral capecitabine twice daily on days 1-14, vinorelbine IV over 6-10 minutes on days 1 and 8, and trastuzumab (Herceptin^®) IV over 30-90 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Patients are followed every 3 months until disease progression and then every 6 months for up to 5 years.

PROJECTED ACCRUAL: A total of 5-47 patients will be accrued for this study within 23 months.

  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 invasive breast cancer

    • Metastatic disease
  • HER2/neu-positive by immunohistochemistry (3+ by HercepTest^™ or equivalent) OR positive for amplification by fluorescent in situ hybridization

    • Testing may be performed in the primary tumor or the metastatic site
  • Received prior anthracycline or taxane as adjuvant therapy or for metastatic disease
  • Measurable disease

    • At least one measurable lesion ≥ 2.0 cm by CT scan or MRI OR ≥ 1.0 cm by spiral CT scan
    • The following are considered non-measurable disease:

      • Bone lesions
      • Leptomeningeal disease
      • Ascites
      • Pleural/pericardial effusion
      • Inflammatory breast disease
      • Lymphangitis cutis/pulmonis
      • Abdominal masses that are not confirmed and followed by imaging techniques
      • Cystic lesions
  • No bone metastases as the only evidence of metastasis
  • Previously treated CNS metastases allowed provided disease has been stable for ≥ the past 3 months
  • Hormone receptor status:

    • Not specified

PATIENT CHARACTERISTICS:

Age

  • 18 and over

Sex

  • Female or male

Menopausal status

  • Not specified

Performance status

  • ECOG 0-2

Life expectancy

  • At least 12 weeks

Hematopoietic

  • Absolute neutrophil count ≥ 1,500/mm^3
  • Hemoglobin ≥ 8.0 g/dL
  • Platelet count ≥ 100,000/mm^3
  • No known uncontrolled coagulopathy

Hepatic

  • Bilirubin ≤ 3.0 times the upper limit of normal (ULN)
  • One of the following must be true:

    • AST or ALT ≤ 5 times ULN AND alkaline phosphatase normal
    • Alkaline phosphatase ≤ 5 times ULN AND AST or ALT normal
    • Alkaline phosphatase ≤ 2.5 times ULN AND AST or ALT ≤ 1.5 times ULN
  • INR ≤ 1.5 times ULN

Renal

  • Calcium ≤ 11.5 mg/dL
  • Creatinine ≤ 1.5 times ULN
  • Creatinine clearance ≥ 30 mL/min

Cardiovascular

  • LVEF ≥ 50% by MUGA or echocardiogram
  • No clinically significant (i.e., active) cardiac disease
  • No congestive heart failure
  • No symptomatic coronary artery disease
  • No myocardial infarction within the past 12 months
  • No cardiac arrhythmia not controlled with medication

Gastrointestinal

  • Able to take oral medication
  • No lack of physical integrity of the upper gastrointestinal tract
  • No clinically significant malabsorption syndrome

Other

  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception during and for 30 days after study participation
  • No history of allergy or hypersensitivity to study drugs, drug product excipients, including polysorbate 80, or chemically similar agents
  • No prior unanticipated severe reaction to fluoropyrimidine therapy
  • No know hypersensitivity to fluorouracil
  • No known dihydropyrimidine dehydrogenase deficiency
  • No history of uncontrolled seizures or CNS disorders
  • No clinically significant psychiatric disability that would preclude giving informed consent or study compliance
  • No other serious uncontrolled infection or disease
  • No other malignancy within the past 5 years except cured basal cell skin cancer, carcinoma in situ of the cervix, or contralateral breast cancer

PRIOR CONCURRENT THERAPY:

Biologic therapy

  • Prior adjuvant trastuzumab (Herceptin^®) allowed as adjuvant or first-line therapy for metastatic disease
  • No concurrent immunotherapy

Chemotherapy

  • See Disease Characteristics
  • No more than 1 prior chemotherapy regimen in the advanced or metastatic (non-adjuvant) setting
  • No prior continuous (≥ 24 hours) fluorouracil infusion
  • No prior capecitabine
  • No prior oral fluoropyrimidines (e.g., eniluracil and fluorouracil, uracil and tegafur, S1, or emitefur)

Endocrine therapy

  • At least 1 day since prior hormonal therapy
  • No concurrent hormonal therapy

Radiotherapy

  • More than 4 weeks since prior radiotherapy to the axial skeleton (i.e., skull, spinal column, sternum, or ribs)
  • No concurrent radiotherapy

Surgery

  • More than 4 weeks since prior major surgery
  • No prior organ allografts requiring immunosuppressive therapy

Other

  • More than 4 weeks since prior investigational drugs
  • No concurrent sorivudine or its chemically related analogues (e.g., brivudine)
  • No concurrent allopurinol, metronidazole, or cimetidine
  • No other concurrent cytotoxic agents
  • No other concurrent investigational drugs
  • No other concurrent anticancer therapy
  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: NCT00093808

  Show 147 Study Locations
Sponsors and Collaborators
North Central Cancer Treatment Group
Investigators
Study Chair: Winston Tan, MD, FACP Mayo Clinic
Investigator: Muhammad Salim, MD Saskatchewan Cancer Agency
Investigator: Edith A. Perez, MD Mayo Clinic
  More Information

Additional Information:
Publications:
Responsible Party: Jan C. Buckner, North Central Cancer Treatment Group
ClinicalTrials.gov Identifier: NCT00093808     History of Changes
Other Study ID Numbers: CDR0000390344, NCCTG-N0337
Study First Received: October 6, 2004
Last Updated: June 17, 2012
Health Authority: United States: Federal Government

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

Additional relevant MeSH terms:
Breast Neoplasms
Breast Diseases
Neoplasms
Neoplasms by Site
Skin Diseases
Capecitabine
Trastuzumab
Vinorelbine
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Antineoplastic Agents, Phytogenic
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on October 28, 2014