A Phase III Clinical Trial Comparing Trastuzumab Given Concurrently With Radiation Therapy and Radiation Therapy Alone for Women With HER2-Positive Ductal Carcinoma In Situ Resected by Lumpectomy
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 2,014
- 试验地点
- 1,251
- 主要终点
- Ipsilateral Invasive Breast Cancer, Ipsilateral Skin Cancer Recurrence, or Ipsilateral DCIS-Free Survival
研究概览
简要总结
This randomized phase III trial studies radiation therapy to see how well it works with or without trastuzumab in treating women with ductal carcinoma in situ who have undergone lumpectomy. 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. Radiation therapy uses high-energy x-rays to kill tumor cells. It is not yet known whether radiation therapy is more effective with or without trastuzumab in treating ductal carcinoma in situ.
详细描述
PRIMARY OBJECTIVES:
I. To determine the value of trastuzumab given during radiation therapy (RT) compared to RT alone in preventing subsequent occurrence of ipsilateral breast cancer recurrence, ipsilateral skin cancer recurrence, or ipsilateral ductal carcinoma in situ (IIBCR-SCR-DCIS) in women with human epidermal growth factor receptor 2 (HER2)-positive DCIS resected by lumpectomy.
SECONDARY OBJECTIVES:
I. Determine the value of trastuzumab given during RT compared to RT alone in prolonging invasive or DCIS disease-free survival (IDFS)-DCIS.
II. Determine the value of trastuzumab given during RT compared to RT alone in increasing invasive or DCIS recurrence-free interval.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 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
- •The patient must have consented to participate and must have signed and dated an appropriate Institutional Review Board (IRB)-approved consent form that conforms to federal and institutional guidelines for the study treatment and for the pre-entry tumor block submission for HER2 testing and B-43 correlative studies
- •Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 (0 = fully active, able to carry on all pre-disease performance without restriction; 1 = restricted in physically strenuous activity but ambulatory)
- •On histologic examination, the tumor must be ductal carcinoma in situ (DCIS) (patients with mixed DCIS and lobular carcinoma in situ [LCIS] are eligible)
- •The DCIS must be HER2-positive as determined by central testing
- •Estrogen and/or progesterone receptor status must be determined prior to randomization (patients with DCIS that is hormone receptor positive or negative are eligible)
- •All DCIS must have been resected by lumpectomy
- •The margins of the resected specimen must be histologically free of DCIS; for patients in whom pathologic examination demonstrates DCIS present at the line of resection, re-excision(s) may be performed to obtain clear margins (patients who require mastectomy are not eligible)
- •If axillary staging is performed, nodal staging must be pN0, pN0(i-), pN0(i+) which is defined as isolated tumor cells =< 0.2 mm, regardless of the method of detection, i.e., immunohistochemistry (IHC) or hematoxylin & eosin (H&E), pN0(mol-), or pN0(mol+); note: axillary staging is not required
- •The interval between the last surgery for excision of DCIS (lumpectomy or re-excision of lumpectomy margins) and randomization must be no more than 120 days
排除标准
- •Invasive (including microinvasion staged as T1mic) breast cancer (patients with DCIS "suspicious" for microinvasion, but not confirmed, are eligible)
- •Nodal staging of pN1 (including pN1mi) (note: axillary staging is not required)
- •DCIS present in more than one quadrant (multicentric)
- •Masses or clusters of calcification that are clinically or mammographically suspicious unless biopsied and proven to be benign (if DCIS is found, the patient is eligible if the DCIS was in the same quadrant of the ipsilateral breast and was resected with clear margins)
- •Contralateral breast cancer (including DCIS)
- •Whole breast irradiation administered before randomization (partial breast irradiation is prohibited)
- •Prior history of breast cancer, including DCIS (patients with a history of LCIS are eligible)
- •Prior anthracycline chemotherapy for any malignancy
- •Cardiac disease that would preclude the use of the drugs included in the B-43 treatment regimens; this includes but is not confined to:
- •Active cardiac disease:
- •Angina pectoris that requires the use of anti-anginal medication;
- •Ventricular arrhythmias except for benign premature ventricular contractions (PVCs) controlled by medication;
- •Conduction abnormality requiring a pacemaker;
- •Supraventricular and nodal arrhythmias requiring a pacemaker or not controlled with medication; and
- •Clinically significant valvular disease
- •History of cardiac disease:
- •Myocardial infarction documented by elevated cardiac enzymes or persistent regional wall abnormalities on assessment of left ventricular (LV) function;
- •Documented congestive heart failure; or
- •Documented cardiomyopathy
- •Uncontrolled hypertension, i.e., systolic blood pressure [BP] greater than 180 mm/Hg and/or diastolic BP greater than 100 mm/Hg (patients with hypertension that is well controlled on medication are eligible)
- •Other nonmalignant systemic disease that would preclude a patient from receiving trastuzumab or radiation therapy or would prevent prolonged follow-up
- •Other malignancies unless the patient is considered to be disease-free for 5 or more years prior to randomization and is deemed by her physician to be at low risk for recurrence; patients with the following cancers are eligible if diagnosed and treated within the past 5 years: carcinoma in situ of the cervix, carcinoma in situ of the colon, melanoma in situ, and basal cell and squamous cell carcinoma of the skin
- •Pregnancy or lactation at the time of study entry (note: pregnancy testing according to institutional standards should be performed for women of child-bearing potential)
- •Administration of any investigational agent within 30 days before study entry
研究组 & 干预措施
Arm I (standard WBI)
Patients undergo standard WBI over 5-6 weeks.
干预措施: Laboratory Biomarker Analysis (Other)
Arm I (standard WBI)
Patients undergo standard WBI over 5-6 weeks.
干预措施: Whole Breast Irradiation (Radiation)
Arm II (WBI, trastuzumab)
Patients receive trastuzumab IV over 30-90 minutes once in weeks 1 and 4. Patients also undergo WBI as in Arm I.
干预措施: Laboratory Biomarker Analysis (Other)
Arm II (WBI, trastuzumab)
Patients receive trastuzumab IV over 30-90 minutes once in weeks 1 and 4. Patients also undergo WBI as in Arm I.
干预措施: Trastuzumab (Biological)
Arm II (WBI, trastuzumab)
Patients receive trastuzumab IV over 30-90 minutes once in weeks 1 and 4. Patients also undergo WBI as in Arm I.
干预措施: Whole Breast Irradiation (Radiation)
结局指标
主要结局
Ipsilateral Invasive Breast Cancer, Ipsilateral Skin Cancer Recurrence, or Ipsilateral DCIS-Free Survival
时间窗: 5 years
Patients who are free from Ipsilateral Invasive Breast Cancer, Ipsilateral Skin Cancer Recurrence or Ipsilateral DCIS as estimated by (1- cumulative incidence) x 100%.
次要结局
- Incidence of Post-treatment Amenorrhea in Women Who Were Premenopausal at the Time of Study Entry Premenopausal at the Time of Study Entry(18 months)
- Contralateral Breast Cancer (Invasive or DCIS) - Free Survival(5 years)
- Invasive or DCIS Disease-free Survival(5 years)
- Invasive or DCIS Recurrence-free Interval(5 years)
- Invasive Regional or Distant-Free Recurrence(5 years)
- Overall Survival(5 years)