A Study of Weekly Doxorubicin and Daily Oral Cyclophosphamide Plus G-CSF Followed by Weekly Paclitaxel as Neoadjuvant Therapy for Resectable, Hormone Receptor Negative or Hormone Receptor Positive, HER-2/Neu Positive Breast Cancer Followed by a Novel Regimen of Capecitabine, Methotrexate and Vinorelbine for Patients Who Do Not Have Either a Macroscopic or Microscopic Pathologic Complete Response, a Phase II Study
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 50
- 试验地点
- 1
- 主要终点
- Combined Rate of Microscopic pCR and Macroscopic Pathologic Complete Response (mCR)
研究概览
简要总结
This phase II trial studies how well giving combination chemotherapy and filgrastim together before surgery works in treating patients with human epidermal growth receptor 2 (HER2)-positive breast cancer that can be removed by surgery. Drugs used in chemotherapy, such as doxorubicin hydrochloride, cyclophosphamide, and paclitaxel work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving combination chemotherapy before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. 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. Giving doxorubicin hydrochloride, cyclophosphamide, and filgrastim together followed by paclitaxel before surgery may be an effective treatment for breast cancer
详细描述
PRIMARY OBJECTIVES:
I. To assess the pathologic response rate in patients with operable breast cancer treated with a two part, neoadjuvant regimen consisting of weekly doxorubicin (doxorubicin hydrochloride) and daily oral cyclophosphamide given with G-CSF (filgrastim) support for 12 weeks followed weekly paclitaxel for 12 weeks.
SECONDARY OBJECTIVES:
I. To assess the clinical response rate in patients with surgically resectable breast cancer treated with weekly doxorubicin and daily oral cyclophosphamide given with G-CSF support for 12 weeks.
II. To assess the clinical response rate in patients with surgically resectable breast cancer treated with weekly paclitaxel for 12 weeks.
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 known tumor HER-2/neu expression; if determination is "intermediate" by immunohistochemistry, fluorescent in situ hybridization (FISH) must be performed; protocol therapy is determined by HER-2/neu result
- •Have histologically confirmed, operable breast cancer that is either:
- •Hormone receptor (estrogen receptor [ER] or progesterone receptor [PR]) positive and HER2/neu positive or
- •ER/PR negative
- •Have radiographically measurable breast cancer > 1cm (Operable lesions are T1c-T3 and N0-N2a; histologic confirmation should be by core needle biopsy only)
- •Be chemotherapy naïve
- •Eastern Cooperative Oncology Group (ECOG) performance status of =< 2
- •Absolute neutrophil count (ANC) >= 1,500
- •Platelet count >= 100,000
- •Serum creatinine =< 1.5 x international upper limit of normal (IULN)
- •Bilirubin < 2.0
- •Serum glutamic oxaloacetic transaminase (SGOT)/serum glutamic pyruvate transaminase (SGPT) =< 2 x IULN
- •Alkaline phosphatase =< 2 x IULN
- •Have staging studies and tumor assessment prior to registration; staging studies include physical exam with bidimensional tumor measurements and mammography, ultrasound, or magnetic resonance imaging (MRI) to assess tumor volume; sentinel lymph node dissection or axillary needle biopsy must be completed prior to enrollment; MRI and positron emission tomography (PET) (fluorodeoxyglucose [FDG], methoxyisobutylisonitrile [MIBI] and fluoroestradiol [FES]) imaging will be done before enrollment if clinically indicated to assess tumor volume or may be done within the first month of study participation on another institutional protocol
- •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 multi gated acquisition scan (MUGA) prior to enrollment; patients with breast cancer that is HER-2/neu positive who will receive herceptin (trastuzumab) must have an echocardiogram or MUGA scan; the left ventricular ejection fraction (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
- •Women of childbearing potential must have a negative pregnancy test within seven days prior to registration
- •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
- •Primary tumor =< 1 cm, not measurable; inflammatory disease
- •Pregnant or lactating; woman of childbearing potential with either a positive or no pregnancy test at baseline are excluded; postmenopausal woman must have been amenorrheic for at least 12 months to be considered of non-childbearing potential; patients must agree to continue contraception for 30 days from the date of the last study drug administration; woman of childbearing potential not using a reliable and appropriate contraceptive method are excluded
- •Evidence of distant metastatic disease
- •Prior chemotherapy or hormonal therapy for breast cancer
- •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 situ cervical cancer or other stage I or II cancer from which the patient has been disease free for at least 5 years
- •Prior unanticipated severe reaction to fluoropyrimidine therapy, or known sensitivity to 5-fluorouracil
- •Previous enrollment in an investigational drug study within the past four weeks
- •History of uncontrolled seizures, central nervous system disorders, or psychiatric disability judged by the investigator to be clinically significant, precluding informed consent, or interfering with compliance with oral drug intake
- •Patients with cardiac disease that would preclude the use of Adriamycin, Taxol or Herceptin are not eligible
- •Active cardiac disease:
- •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 electrocardiogram (EKG)
- •Uncontrolled hypertension, (diastolic greater than 100 mm/Hg or systolic > 200 mm/hg)
- •Current use of digitalis or beta blockers for congestive heart failure (CHF)
- •Clinically significant pericardial effusion
- •History of cardiac disease:
- •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
- •Major surgery within 4 weeks of the start of study treatment without complete recovery
- •Lack of physical integrity of the upper gastrointestinal tract or malabsorption syndrome
- •Known, existing uncontrolled coagulopathy
- •Unwillingness to give written informed consent
- •Unwillingness to participate or inability to comply with the protocol for the duration of the study
研究组 & 干预措施
Treatment (neoadjuvant therapy, adjuvant therapy)
See Detailed Description.
干预措施: doxorubicin hydrochloride (Drug)
Treatment (neoadjuvant therapy, adjuvant therapy)
See Detailed Description.
干预措施: cyclophosphamide (Drug)
Treatment (neoadjuvant therapy, adjuvant therapy)
See Detailed Description.
干预措施: paclitaxel (Drug)
Treatment (neoadjuvant therapy, adjuvant therapy)
See Detailed Description.
干预措施: filgrastim (Biological)
Treatment (neoadjuvant therapy, adjuvant therapy)
See Detailed Description.
干预措施: capecitabine (Drug)
Treatment (neoadjuvant therapy, adjuvant therapy)
See Detailed Description.
干预措施: methotrexate (Drug)
Treatment (neoadjuvant therapy, adjuvant therapy)
See Detailed Description.
干预措施: vinorelbine tartrate (Drug)
Treatment (neoadjuvant therapy, adjuvant therapy)
See Detailed Description.
干预措施: needle biopsy (Procedure)
Treatment (neoadjuvant therapy, adjuvant therapy)
See Detailed Description.
干预措施: therapeutic conventional surgery (Procedure)
Treatment (neoadjuvant therapy, adjuvant therapy)
See Detailed Description.
干预措施: immunohistochemistry staining method (Other)
Treatment (neoadjuvant therapy, adjuvant therapy)
See Detailed Description.
干预措施: trastuzumab (Biological)
Treatment (neoadjuvant therapy, adjuvant therapy)
See Detailed Description.
干预措施: tamoxifen citrate (Drug)
Treatment (neoadjuvant therapy, adjuvant therapy)
See Detailed Description.
干预措施: letrozole (Drug)
Treatment (neoadjuvant therapy, adjuvant therapy)
See Detailed Description.
干预措施: laboratory biomarker analysis (Other)
结局指标
主要结局
Combined Rate of Microscopic pCR and Macroscopic Pathologic Complete Response (mCR)
时间窗: Up to 16 weeks
Microscopic pCR: No evidence of microscopic invasive tumor at the primary site or in the regional lymph nodes at the time of definitive surgical resection. mCR: The examining pathologist cannot identify gross residual tumor mass in the surgical specimen. This differs from a pCR where the specimen must also be negative for invasive tumor by microscopy. For this study, we are using a definition of mCR that will make the trial more translatable to other institutions. For this study, mCR will be defined as no focus of invasive cancer \>= 1 cm. Count of participants with either a pCR or mCR.
次要结局
- Number and Percent of Patients Reporting Grade 2, 3, 4, or Fatal Toxicities of These Regimens, Need for Dose Reduction, or Treatment Interruption or Discontinuation(From the initiation of study treatments to 30 days after the end of neoadjuvant treatment or adjuvant treatment if received)
- Correlation of Molecular Markers With Response(After completion of neoadjuvant therapy)
- Relapse Rate in Patients With Operable Breast Cancer Treated With Neoadjuvant Chemotherapy for 12 Weeks Followed by Weekly Paclitaxel for 12 Weeks and Adjuvant Chemotherapy(Up to 8 years)
- Time to Progression(Up to 5 years)
- OS in Patients With Operable Breast Cancer Treated With Neoadjuvant Chemotherapy for 12 Weeks Followed Weekly Paclitaxel for 12 Weeks and Adjuvant Chemotherapy With XMN(1, 2, and 5 years)
- Disease-free Survival(1, 2, and 5 years)
- Clinical Response to Neoadjuvant Therapy(Up to 12 weeks)
- Clinical Response to Paclitaxel(Up to 24 weeks)
研究者
Hannah Linden
Investigator
University of Washington