Adjuvant Therapy for High-Risk Localized Breast Cancer Using Weekly Adriamycin + Daily Oral Cytoxan With Continuous G-CSF Support for 12 Weeks Followed by Weekly Abraxane™ for 12 Weeks With Concurrent Herceptin for Subjects With HER-2/Neu Positive Disease, Phase II
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 60
- 试验地点
- 1
- 主要终点
- Disease-free Survival Following a Dose-intensive Weekly Regimen of Adriamycin + Oral Cyclophosphamide Augmented With G-CSF Support Followed by Abraxane and Herceptin
研究概览
简要总结
RATIONALE: Drugs used in chemotherapy, such as doxorubicin hydrochloride, cyclophosphamide, and paclitaxel albumin-stabilized nanoparticle formulation, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Colony-stimulating factors, such as filgrastim, may increase the number of immune cells found in bone marrow or peripheral blood and may help the immune system recover from the side effects of chemotherapy. 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. Giving combination chemotherapy and filgrastim together with trastuzumab may kill more tumor cells.
PURPOSE: This phase II trial is studying how well giving doxorubicin hydrochloride, cyclophosphamide, and filgrastim together followed by paclitaxel albumin-stabilized nanoparticle formulation and trastuzumab works in treating patients with breast cancer previously treated with surgery
详细描述
PRIMARY OBJECTIVES:
I. To assess disease-free survival following a dose-intensive weekly regimen of Adriamycin + oral cyclophosphamide augmented with G-CSF support followed by Abraxane and Herceptin if appropriate for adjuvant treatment of high risk breast cancer patients.
SECONDARY OBJECTIVES:
I. To assess the toxicity associated with this regimen. II. To assess the delivered dose intensity of the regimen. III. To assess time to treatment failure and overall survival of the regimen. IV. To assess the incidence and severity of delayed nausea and vomiting with this regimen.
OUTLINE:
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Have a histologically confirmed diagnosis of primary breast carcinoma that has been surgically resected; (this regimen is not intended for neoadjuvant treatment)
- •4 + nodes
- •OR if 1-3 + nodes, either ER OR HER-2/neu+
- •OR have high-risk node negative disease that is HER-2/neu positive OR >= 2.0 cm tumor size
- •HER-2/new + definition: patient has known tumor HER-2/new expression = 3+ by IHC or, if 2+ by IHC confirmed to be FISH positive
- •Patients with clinically apparent cardiac disease, or history of same, are not eligible; patients who are >= 60 years of age or who have a history of hypertension must have an echocardiogram or MUGA prior to enrollment; patients with breast cancer that is HER-2/neu positive and a treatment plan that includes Herceptin must have an echocardiogram or MUGA scan prior to enrollment; the LVEF must be within the institutional normal range; if LVEF is > 75%, the investigator should consider having the LVEF reviewed or repeating the MUGA prior to registration
- •WBC >= 4,000
- •ANC >= 1,500
- •Platelet count >= 100,000
- •Serum creatinine =< 1.5 x IULN
- •Bilirubin =< 2.0
- •SGOT/SGPT/alkaline phosphatase =< 2 x IULN
- •Elevations greater than these require metastatic work up
- •Be informed of the investigational nature of this study and provide written informed consent in accordance with institutional and federal guidelines prior to study specific screening procedures
排除标准
- •Except for the following, no other malignancy is allowed: synchronous ipsilateral breast cancer of the same subtype (ER/PR, HER-2/neu), adequately treated basal cell or squamous cell skin cancer, in situcervical cancer or other stage I or II cancer from which the patient has been disease free for at least 5 years
- •Patients with cardiac disease that would preclude the use of Adriamycin, Taxol or Herceptin are not eligible; this includes:
- •Angina pectoris that requires the use of antianginal medication
- •Cardiac arrhythmia requiring medication
- •Severe conduction abnormality
- •Clinically significant valvular disease
- •Cardiomegaly on chest x-ray
- •Ventricular hypertrophy on EKG
- •Uncontrolled hypertension, (diastolic greater than 100 mm/Hg or systolic > 200 mm/hg)
- •Current use of digitalis or beta blockers for CHF
- •Clinically significant pericardial effusion
- •Myocardial infarction documented as a clinical diagnosis or by EKG or any other test
- •Documented congestive heart failure
- •Documented cardiomyopathy
- •Documented arrhythmia or cardiac valvular disease that requires medication or is medically significant
- •Patients who have received prior chemotherapy or radiotherapy are not eligible
- •Patients who are pregnant or breastfeeding are not eligible; women of child bearing potential must agree to practice adequate contraception
- •Patients with active infection are not eligible
- •Patients who are known to be infected with HIV, hepatitis B or hepatitis C are not eligible; testing is not required unless there is a high index of clinical suspicion
- •Patients suffering from psychiatric impairment are not eligible
研究组 & 干预措施
Arm I
Patients receive dose-intensive chemotherapy comprising doxorubicin hydrochloride IV over 10-15 minutes on day 1, oral cyclophosphamide once daily on days 1-7, and filgrastim subcutaneously on days 2-7. Courses repeat every 7 days for up to 12 weeks in the absence of disease progression or unacceptable toxicity. Beginning 1 week later, patients then receive paclitaxel albumin-stabilized nanoparticle formulation IV over 30 minutes once a week for 12 weeks in the absence of disease progression or unacceptable toxicity. Patients with HER-2/neu positive disease also receive trastuzumab IV over 30-90 minutes once a week for 1 year in the absence of disease progression or unacceptable toxicity.
干预措施: doxorubicin hydrochloride (Drug)
Arm I
Patients receive dose-intensive chemotherapy comprising doxorubicin hydrochloride IV over 10-15 minutes on day 1, oral cyclophosphamide once daily on days 1-7, and filgrastim subcutaneously on days 2-7. Courses repeat every 7 days for up to 12 weeks in the absence of disease progression or unacceptable toxicity. Beginning 1 week later, patients then receive paclitaxel albumin-stabilized nanoparticle formulation IV over 30 minutes once a week for 12 weeks in the absence of disease progression or unacceptable toxicity. Patients with HER-2/neu positive disease also receive trastuzumab IV over 30-90 minutes once a week for 1 year in the absence of disease progression or unacceptable toxicity.
干预措施: cyclophosphamide (Drug)
Arm I
Patients receive dose-intensive chemotherapy comprising doxorubicin hydrochloride IV over 10-15 minutes on day 1, oral cyclophosphamide once daily on days 1-7, and filgrastim subcutaneously on days 2-7. Courses repeat every 7 days for up to 12 weeks in the absence of disease progression or unacceptable toxicity. Beginning 1 week later, patients then receive paclitaxel albumin-stabilized nanoparticle formulation IV over 30 minutes once a week for 12 weeks in the absence of disease progression or unacceptable toxicity. Patients with HER-2/neu positive disease also receive trastuzumab IV over 30-90 minutes once a week for 1 year in the absence of disease progression or unacceptable toxicity.
干预措施: filgrastim (Biological)
Arm I
Patients receive dose-intensive chemotherapy comprising doxorubicin hydrochloride IV over 10-15 minutes on day 1, oral cyclophosphamide once daily on days 1-7, and filgrastim subcutaneously on days 2-7. Courses repeat every 7 days for up to 12 weeks in the absence of disease progression or unacceptable toxicity. Beginning 1 week later, patients then receive paclitaxel albumin-stabilized nanoparticle formulation IV over 30 minutes once a week for 12 weeks in the absence of disease progression or unacceptable toxicity. Patients with HER-2/neu positive disease also receive trastuzumab IV over 30-90 minutes once a week for 1 year in the absence of disease progression or unacceptable toxicity.
干预措施: paclitaxel albumin-stabilized nanoparticle formulation (Drug)
Arm I
Patients receive dose-intensive chemotherapy comprising doxorubicin hydrochloride IV over 10-15 minutes on day 1, oral cyclophosphamide once daily on days 1-7, and filgrastim subcutaneously on days 2-7. Courses repeat every 7 days for up to 12 weeks in the absence of disease progression or unacceptable toxicity. Beginning 1 week later, patients then receive paclitaxel albumin-stabilized nanoparticle formulation IV over 30 minutes once a week for 12 weeks in the absence of disease progression or unacceptable toxicity. Patients with HER-2/neu positive disease also receive trastuzumab IV over 30-90 minutes once a week for 1 year in the absence of disease progression or unacceptable toxicity.
干预措施: trastuzumab (Biological)
Arm I
Patients receive dose-intensive chemotherapy comprising doxorubicin hydrochloride IV over 10-15 minutes on day 1, oral cyclophosphamide once daily on days 1-7, and filgrastim subcutaneously on days 2-7. Courses repeat every 7 days for up to 12 weeks in the absence of disease progression or unacceptable toxicity. Beginning 1 week later, patients then receive paclitaxel albumin-stabilized nanoparticle formulation IV over 30 minutes once a week for 12 weeks in the absence of disease progression or unacceptable toxicity. Patients with HER-2/neu positive disease also receive trastuzumab IV over 30-90 minutes once a week for 1 year in the absence of disease progression or unacceptable toxicity.
干预措施: laboratory biomarker analysis (Other)
Arm I
Patients receive dose-intensive chemotherapy comprising doxorubicin hydrochloride IV over 10-15 minutes on day 1, oral cyclophosphamide once daily on days 1-7, and filgrastim subcutaneously on days 2-7. Courses repeat every 7 days for up to 12 weeks in the absence of disease progression or unacceptable toxicity. Beginning 1 week later, patients then receive paclitaxel albumin-stabilized nanoparticle formulation IV over 30 minutes once a week for 12 weeks in the absence of disease progression or unacceptable toxicity. Patients with HER-2/neu positive disease also receive trastuzumab IV over 30-90 minutes once a week for 1 year in the absence of disease progression or unacceptable toxicity.
干预措施: quality-of-life assessment (Procedure)
结局指标
主要结局
Disease-free Survival Following a Dose-intensive Weekly Regimen of Adriamycin + Oral Cyclophosphamide Augmented With G-CSF Support Followed by Abraxane and Herceptin
时间窗: 2 years
次要结局
- Time to Treatment Failure(Up to 6 years)
- Delivered Dose Intensity of the Regimen(After at least one course of Adriamycin, up to 12 weeks.)
- Toxicity Associated With This Regimen(After at least one course of Adriamycin, up to 12 weeks.)
- Overall Survival(Up to 6 years.)
研究者
Vijayakrishna Gadi
Investigator
University of Washington