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

This study has been completed.
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Alliance for Clinical Trials in Oncology
ClinicalTrials.gov Identifier:
NCT00093808
First received: October 6, 2004
Last updated: January 23, 2017
Last verified: January 2017
  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: Intervention Model: Single Group Assignment
Masking: No masking
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 Alliance for Clinical Trials in Oncology:

Primary Outcome Measures:
  • Confirmed Response Rate [ Time Frame: Up to 5 years ]
    A confirmed tumor response is defined to be either a Complete Response (CR) or Partial Response (PR) noted as the objective status on 2 consecutive evaluations at least 6 weeks apart. All patients meeting the eligibility criteria who have signed a consent form and initiated study medication will be evaluable for response. The proportion of confirmed tumor responses will be estimated by the number of tumor regressions that meet the RECIST criteria for a confirmed CR or PR divided by the total number of evaluable patients. A 95% confidence interval for the true confirmed response rate will be calculated using the properties of the binomial distribution. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.


Secondary Outcome Measures:
  • Time to Progression (TTP) [ Time Frame: Up to 5 years ]
    Time to progression is defined as the time from registration to disease progression. Patients who died without documentation of progression will be considered to have progressed on the date of their death. If a patient starts treatment and fails to return for any evaluations, that patient will be censored for progression of disease at day one post-registration. Otherwise, for patients that do not progress, censoring will occur at the last follow up date. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as at least a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions or unequivocal progression of existing non-target lesions.

  • Duration of Response as Measured by RECIST Criteria [ Time Frame: Up to 5 years ]
    Duration of response is defined for all eligible patients who have achieved an objective response as the date at which the patient's objective status is first noted to be either a Complete Response (CR) or Partial Response (PR) to the date progression is documented. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions.

  • Overall Survival as Assessed by Time [ Time Frame: Up to 5 years ]
    Overall survival: The overall survival or survival time is defined as the time from registration to death due to any cause. The distribution of overall survival will be estimated using the method of Kaplan-Meier method.


Enrollment: 47
Study Start Date: August 2004
Study Completion Date: May 2013
Primary Completion Date: December 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: capecitabine + vinorelbine + trastuzumab

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.

Biological: trastuzumab Drug: capecitabine Drug: vinorelbine tartrate

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.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
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

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
Alliance for Clinical Trials in Oncology
National Cancer Institute (NCI)
Investigators
Study Chair: Winston Tan, MD, FACP Mayo Clinic
  More Information

Publications:
Responsible Party: Alliance for Clinical Trials in Oncology
ClinicalTrials.gov Identifier: NCT00093808     History of Changes
Other Study ID Numbers: NCCTG-N0337
NCI-2012-02625 ( Registry Identifier: CTRP (Clinical Trials Reporting System) )
CDR0000390344 ( Registry Identifier: PDQ (Physician Data Query) )
Study First Received: October 6, 2004
Results First Received: November 28, 2016
Last Updated: January 23, 2017

Keywords provided by Alliance for Clinical Trials in Oncology:
recurrent breast cancer
stage IV breast cancer
male breast cancer

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Vinorelbine
Trastuzumab
Capecitabine
Vinblastine
Antineoplastic Agents
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Phytogenic
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators

ClinicalTrials.gov processed this record on May 25, 2017