TRIAL COMPARING ADJUVANT CLODRONATE THERAPY VERSUS PLACEBO IN BREAST CANCER

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。这项III期前瞻性、随机、双盲、安慰剂对照试验将评估氯膦酸盐（第二代双膦酸盐）在早期乳腺癌患者中的价值。为了有资格参加这项试验，妇女必须接受全乳房切除术或乳房肿瘤切除术，同时进行腋窝清扫或前哨淋巴结活检。对于接受前哨淋巴结活检的患者，只有参加NSABP B-32的患者才有资格。如果在B-32方案之外进行前哨淋巴结活检，则需要完成腋窝清扫。患者将根据年龄、淋巴结状态、ER和/或PgR受体状态进行分层。患者必须没有转移性疾病的证据。辅助化疗和/或他莫昔芬的管理将由研究者自行决定，并将记录在研究记录中。确切的治疗方案、剂量和持续时间将由研究者自行决定。患者将在前5年每6个月随访一次，之后每12个月随访一次。为了充分确定对骨和所有其他潜在复发部位的治疗效果，将对每位患者进行复发部位随访，直到发生骨和非骨转移（包括内脏部位、软组织部位和/或局部/区域复发部位）。患者将继续其指定的治疗3年或直到第一次明确的骨转移，即使患者先前有非骨骼复发或第二原发癌症。该试验的主要目的是：1)确定连续3年每天服用1600mg氯膦酸钠，单独服用或与辅助化疗和/或激素治疗联合使用，是否会改善无病生存期；2)评估氯膦酸钠佐剂是否能降低骨骼转移、骨骼相关发病率、非骨骼转移、改善无复发生存期和总生存期；3)探讨骨转化血清标志物作为骨转移发生的预后因素的相关性。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. This phase III prospective randomized, double-blind, placebo-controlled trial will evaluate the worth of clodronate, a second-generation biphosphonate, in women with early-stage breast cancer. To qualify for this trial, women must have undergone either a total mastectomy or a lumpectomy with either an axillary dissection or sentinel node biopsy. For patients undergoing sentinel node biopsy, only those participating in NSABP B-32 will be eligible. If sentinel node biopsy is performed outside the B-32 protocol, completion of axillary dissection is required. Patients will be stratified according to age, nodal status and ER and/or PgR receptor status. Patients must have no evidence of metastatic disease. The administration of adjuvant chemotherapy and/or tamoxifen will be at the discretion of the investigator and will be documented in the study record. The exact regimen, dose and duration wil be at the discretion of the investigator. Patients will be followed every six months for the first five years and every 12 months thereafter. In order to fully determine treatment effects on both bone and all other potential sites of recurrence, each patient will be followed for sites of recurrence until the development of both bone and non-bone metastasis (this includes visceral sites, soft tissue sites and/or local/regional recurrence sites) have occurred. Patients will continue their assigned therapy for three years or until first definite bone metastasis, even if the patient has had a prior non-skeletal recurrence or second primary cancer. The primary aims of this trial are: 1) to determine whether 1,600 mg/day of clodronate, given for three years, either alone or in addition to adjuvant chemotherapy and/or hormonal therapy will improve disease-free survival; 2) to evaluate whether adjuvant clodronate results in a reduction in skeletal metastases, skeletal-related morbidity, non-skeletal metastases, and an improvement in relapse-free survival and overall survival; and 3) to investigate the relevance of serum markers of bone turnover as a prognostic factor for the development of bone metastases.