A Phase III Trial Evaluating The Role Of Exemestane Plus GnRH Analogue As Adjuvant Therapy For Premenopausal Women With Endocrine Responsive Breast Cancer
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 2,672
- 试验地点
- 228
- 主要终点
- Disease-free Survival
研究概览
简要总结
RATIONALE: Estrogen can stimulate the growth of breast cancer cells. Hormone therapy using triptorelin, exemestane, and tamoxifen may fight breast cancer by blocking the use of estrogen. It is not yet known whether giving triptorelin together with exemestane is more effective than triptorelin and tamoxifen in treating hormone-responsive breast cancer.
PURPOSE: This randomized phase III trial is studying triptorelin and exemestane to see how well they work compared to triptorelin and tamoxifen in treating premenopausal women with hormone-responsive breast cancer.
详细描述
OBJECTIVES:
- Compare the disease-free survival, breast cancer-free interval, distant recurrence-free interval and overall survival of premenopausal women with endocrine-responsive breast cancer when treated with triptorelin and exemestane vs triptorelin and tamoxifen.
- Compare the quality of life, including late side effects of early menopause, of patients treated with these regimens.
OUTLINE: This is a randomized, international, multicenter study. Patients are stratified according to planned use of concurrent adjuvant chemotherapy (yes vs no), and number of positive lymph nodes (0 vs 1 or more). Treatment duration is 5 years. Patients are followed every 3 months for 1 year, every 6 months for 5 years, and then annually thereafter. Quality of life is assessed at baseline, every 6 months for 2 years, and annually for 3 years.
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 65 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •DISEASE CHARACTERISTICS:
- •Histologically confirmed breast cancer
- •Completely resected disease
- •No clinically detectable residual loco-regional axillary disease
- •Prior surgery for primary breast cancer of 1 of the following types:
- •Total mastectomy with or without adjuvant radiotherapy
- •Breast-conserving procedure (e.g., lumpectomy, quadrantectomy, or partial mastectomy with margins negative* for invasive disease and ductal carcinoma in situ) with planned radiotherapy NOTE: *If all other margins are clear a positive posterior (deep) margin is permitted, provided the excision was performed down to the pectoral fascia and all tumor has been removed OR a positive anterior (superficial; abutting skin) margin is allowed provided all tumor was removed
- •Tumor confined to the breast and axillary nodes
- •Tumor detected in internal mammary chain nodes by sentinel node procedure and is not enlarged is allowed
- •Axillary lymph node dissection or a negative axillary sentinel node biopsy required
- •Patients with negative or microscopically positive axillary sentinel nodes are eligible
- •Positive sentinel nodes must have either axillary dissection or radiation of axillary nodes
- •No distant metastases
- •No locally advanced inoperable breast cancer, including any of the following:
- •Inflammatory breast cancer
- •Supraclavicular node involvement
- •Enlarged internal mammary nodes (unless pathologically negative)
- •Bilateral synchronous invasive breast cancer allowed if disease meets all other eligibility criteria
- •No prior ipsilateral or contralateral invasive breast cancer
- •Hormone receptor status:
- •Estrogen and/or progesterone receptor positive
- •At least 10% of the tumor cells positive by immunohistochemistry
- •If > 1 breast tumor, each tumor must be hormone receptor positive
- •PATIENT CHARACTERISTICS:
- •Premenopausal
- •Menopausal status
- •Premenopausal
- •Estradiol in the premenopausal range after prior surgery OR meets the following criteria:
- •Menstruating regularly for the past 6 months
- •Has not used any form of hormonal treatment (including hormonal contraception) within the past 6 months
- •Performance status
- •Not specified
- •Life expectancy
- •Not specified
- •Hematopoietic
- •Not specified
- •No systemic hepatic disease that would preclude prolonged follow-up
- •No systemic renal disease that would preclude prolonged follow-up
- •Cardiovascular
- •No systemic cardiovascular disease that would preclude prolonged follow-up
- •No prior thrombosis (e.g., deep vein thrombosis) and/or embolism unless patient is medically suitable
- •No systemic pulmonary disease that would preclude prolonged follow-up
- •Not pregnant or nursing
- •Fertile patients must use effective nonhormonal contraception
- •No history of noncompliance to medical regimens
- •No other nonmalignant systemic disease that would preclude prolonged follow-up
- •No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer, nonbreast carcinoma in situ, contralateral or ipsilateral carcinoma in situ of the breast, or other nonrecurrent invasive nonbreast malignancy, including any of the following:
- •Stage I papillary thyroid cancer
- •Stage IA carcinoma of the cervix
- •Stage IA or B endometrioid endometrial cancer
- 另有 23 项未显示
排除标准
- 未提供
研究组 & 干预措施
T+OFS
Ovarian function suppression (OFS) by triptorelin (GnRH analogue) 3.75mg by im injection q28 days for 5 years plus tamoxifen 20mg orally daily for 5 years. Tamoxifen (T) begins after the completion of adjuvant chemotherapy if given, or approximately 6-8 weeks after the initiation of triptorelin. Bilateral oophorectomy or ovarian irradiation was allowed after at least 6 months of triptorelin.
干预措施: tamoxifen (Drug)
T+OFS
Ovarian function suppression (OFS) by triptorelin (GnRH analogue) 3.75mg by im injection q28 days for 5 years plus tamoxifen 20mg orally daily for 5 years. Tamoxifen (T) begins after the completion of adjuvant chemotherapy if given, or approximately 6-8 weeks after the initiation of triptorelin. Bilateral oophorectomy or ovarian irradiation was allowed after at least 6 months of triptorelin.
干预措施: triptorelin (Drug)
E+OFS
Ovarian function suppression (OFS) by triptorelin (GnRH analogue) 3.75mg by im injection q28 days for 5 years plus exemestane 25mg orally daily for 5 years. Exemestane (E) begins after the completion of adjuvant chemotherapy if given, or approximately 6-8 weeks after the initiation of triptorelin. Bilateral oophorectomy or ovarian irradiation was allowed after at least 6 months of triptorelin.
干预措施: exemestane (Drug)
E+OFS
Ovarian function suppression (OFS) by triptorelin (GnRH analogue) 3.75mg by im injection q28 days for 5 years plus exemestane 25mg orally daily for 5 years. Exemestane (E) begins after the completion of adjuvant chemotherapy if given, or approximately 6-8 weeks after the initiation of triptorelin. Bilateral oophorectomy or ovarian irradiation was allowed after at least 6 months of triptorelin.
干预措施: triptorelin (Drug)
结局指标
主要结局
Disease-free Survival
时间窗: 5-year estimate reported at a median follow-up of 72 months
Estimated percentage of patients alive and disease-free at 5 years from randomization, where disease-free survival is defined as the time from randomization to the first appearance of one of the following: invasive breast cancer recurrence at local, regional, or distant site, invasive contralateral breast cancer, second (non-breast) invasive cancer, or death without cancer event; or censored at date of last follow up.
次要结局
- Breast Cancer-free Interval(5-year estimate reported at a median follow-up of 72 months)
- Distant Recurrence-free Interval(5-year estimates reported at a median follow-up of 72 months)
- Overall Survival(8-year estimates, reported at a median follow-up of 9 years)