Phase III Randomized Study of the Effects on Bone Mineral Density of Tamoxifen, Letrozole, and Letrozole + Zoledronic Acid as Adjuvant Treatment of Patients With Early Breast Cancer; VERSION 2 AMENDED Phase 3 Study of Triptorelin and Tamoxifen, Letrozole, or Letrozole + Zoledronic Acid in Adjuvant Treatment of Premenopausal Endocrine Responsive Breast Cancer Patients.
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 1,294
- 试验地点
- 19
- 主要终点
- disease free survival in premenopausal patients
研究概览
简要总结
The HOBOE study was amended in November 2009, and, after reaching enrollment of the first 500 patients, the study began recruiting premenopausal patients only. The primary objective of the extended study is to compare disease free survival in premenopausal patients with early breast cancer. Patients receive triptorelin and are randomized in a 1:1:1 fashion to receive tamoxifen or letrozole, or letrozole + zoledronic acid.
The purpose of the HOBOE study, Version 1, was to compare the adjuvant hormonal therapy treatments of Tamoxifen, Letrozole and Letrozole + Zoledronate for their effects on bone loss in breast cancer patients. Postmenopausal and premenopausal patients were eligible, the latter also receiving monthly triptorelin. Upon reaching the enrollment of the first 500 patients in March 2010, the study began recruiting premenopausal patients only.
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
- •Histological diagnosis of breast cancer
- •Surgical resection of breast cancer (breast conserving surgery or mastectomy)
- •No evidence of disease
- •Indication for adjuvant hormonal therapy (ER and/or PgR positive with IHC exam in at least 1% of primary tumor cells, according to St. Gallen criteria)
- •Patient age at least 18 years
- •Written informed consent . Premenopausal status defined as LMP within 12 months of randomization (FSH, LH will not be considered as determinants of menopausal status due the chemotherapy induced reversible ovarian suppression)
- •Please note that patients who have received neoadjuvant or adjuvant chemotherapy and/or locoregional radiation therapy may be included in the study
排除标准
- •Performance status (ECOG)>
- •Previous or concomitant malignancy (with the exception of adequately treated nonmalignant skin cancer and carcinoma in situ of the uterine cervix
- •Metastatic breast cancer
- •Creatinine > 1.25 times the value of upper normal limit
- •Pregnant or lactating females
- •Clinical or radiologic evidence of bone fractures
- •Treatment with systemic cortisone therapy within 12 months prior to randomization
- •Treatment with drugs that could alter bone metabolism (calcitonin, mithramycin, gallium nitrate) within 2 weeks prior to randomization
- •Previous treatment with tamoxifen or aromatase inhibitors
- •AST and/or ALT > 3 times the value of upper normal limit with clinical and laboratory findings that indicate a grade of hepatic insufficiency that could potentially increase the risk of assuming letrozole
- •Any concomitant conditions that would, in the Investigator's opinion, contraindicate the use of any of the drugs used in this study
- •Inability to provide informed consent
- •Inability to comply with followup
- •Patient undergoing invasive dental work at time of baseline evaluation or foreseen during the course of adjuvant therapy
研究组 & 干预措施
A
Triptorelin 3.75 mg IM every 4 weeks and Tamoxifen 20 mg daily, for 5 years
干预措施: tamoxifen (Drug)
A
Triptorelin 3.75 mg IM every 4 weeks and Tamoxifen 20 mg daily, for 5 years
干预措施: triptorelin (Drug)
B
Triptorelin 3.75 mg IM every 4 weeks and Letrozole 2.5 mg daily, for 5 years
干预措施: triptorelin (Drug)
B
Triptorelin 3.75 mg IM every 4 weeks and Letrozole 2.5 mg daily, for 5 years
干预措施: letrozole (Drug)
C
Triptorelin 3.75 mg IM every 4 weeks and Letrozole 2.5 mg daily for 5 years + zoledronic acid 4 mg every 6 months.
干预措施: triptorelin (Drug)
C
Triptorelin 3.75 mg IM every 4 weeks and Letrozole 2.5 mg daily for 5 years + zoledronic acid 4 mg every 6 months.
干预措施: letrozole (Drug)
C
Triptorelin 3.75 mg IM every 4 weeks and Letrozole 2.5 mg daily for 5 years + zoledronic acid 4 mg every 6 months.
干预措施: zoledronic acid (Drug)
结局指标
主要结局
disease free survival in premenopausal patients
时间窗: observation period is 10 years from initiation of treatment
bone mineral density
时间窗: 12 months from initiation of therapy
次要结局
- Bone mineral density measured(yearly after first year of therapy)
- overall survival(observation period is 10 years from initiation of treatment)
- toxicity of letrozole + triptorelin and letrozole + zoledronic acid + triptorelin in premenopausal patients(monthly)
- disease free survival in postmenopausal patients(observation period is 10 years from initiation of treatment)