A Phase III Adjuvant Trial Evaluating the Addition of Adjuvant Chemotherapy to Ovarian Function Suppression Plus Endocrine Therapy in Premenopausal Patients With pN0-1, ER-Positive/HER2-Negative Breast Cancer and an Oncotype Recurrence Score Less Than or Equal to 25 (OFSET)
概览
- 阶段
- 3 期
- 干预措施
- Ovarian Function Suppression + Aromatase Inhibitor
- 疾病 / 适应症
- Breast Cancer
- 发起方
- NRG Oncology
- 入组人数
- 3960
- 试验地点
- 2414
- 主要终点
- Invasive breast cancer-free survival (IBCFS)
- 状态
- 招募中
- 最后更新
- 9天前
概览
简要总结
This Phase III Trial will determine whether adjuvant chemotherapy (ACT) added to ovarian function suppression (OFS) plus endocrine therapy (ET) is superior to OFS plus ET in improving invasive breast cancer-free survival (IBCFS) among premenopausal, early- stage breast cancer (EBC) patients with estrogen receptor (ER)-positive, HER2-negative tumors and 21-gene recurrence score (RS) between 16-25 (for pN0 patients) and 0-25 (for pN1 patients).
详细描述
Younger age at diagnosis is an adverse prognostic factor in early breast cancer: women who are less than 35 years of age at diagnosis are more likely to die from their disease than their older counterparts following standard treatments. There remains a pressing need for advancements in therapeutic options for this patient population. One increasingly utilized option is ovarian suppression, which was first reported as treatment for advanced breast cancer in 1896 and has been examined in a multitude of clinical trials over the past century. As chemotherapeutic options became more commonplace for breast cancer therapy, however, the role of ovarian suppression became uncertain. In the pre-genomic era, several studies evaluated the role of ovarian suppression compared to chemotherapy, with conflicting results. These studies either looked at ovarian suppression alone or at tamoxifen compared to chemotherapy. A meta-analysis examining LHRH-agonists (luteinizing hormone-releasing hormone) in the Early Breast Cancer Overview group (LHRH-agonists in Early Breast Cancer Overview group 2007) showed that when LHRH-agonists were added to tamoxifen, chemotherapy, or both, there was a 12.7% reduction in the risk of recurrence and a 15.1% reduction in the risk of death. When compared to chemotherapy, LHRH-agonists appeared to be equally as effective, especially if patients were less than 40 years of age. These older studies, conducted in the pre-taxane/anthracycline era, typically used CMF (cyclophosphamide, methotrexate, and fluorouracil) chemotherapy, and were designed prior to the use of genomic assays .
研究者
入排标准
入选标准
- •A patient cannot be considered eligible for this study unless ALL of the following conditions are met.
- •The patient or a legally authorized representative must provide study-specific informed consent prior to pre-entry and, for patients treated in the U.S., authorization permitting release of personal health information.
- •Female patients must be greater than or equal to 18 years of age.
- •Patients must be premenopausal (evidence of functioning ovaries) at the time of pre-entry. For study purposes, premenopausal is defined as:
- •Age 50 years or under with spontaneous menses within 12 months; or
- •Age greater than 50-60 years with spontaneous menses within 12 months plus follicle-stimulating hormone (FSH) and estradiol levels in the premenopausal range; or
- •Patients with amenorrhea due to IUD or prior uterine ablation must have FSH and estradiol levels in the premenopausal range; or
- •Patients with prior hysterectomy must have FSH and estradiol levels in the premenopausal range.
- •The patient must have an ECOG performance status of less than or equal to 2 (or Karnofsky greater than or equal to 60%).
- •Patients may have ipsilateral or contralateral synchronous breast cancer if the highest stage tumor meets entry criteria, and the other sites of disease would not require chemotherapy or HER2-directed therapy.
排除标准
- •• Definitive clinical or radiologic evidence of metastatic disease.
- •pT4 (pathological state) tumors, including inflammatory breast cancer.
- •History of ipsilateral or contralateral invasive breast cancer. (Patients with synchronous and/or previous DCIS or LCIS are eligible.)
- •If prior ipsilateral DCIS was treated with lumpectomy and XRT (ionizing radiation therapy), a mastectomy must have been performed for the current cancer.
- •Life expectancy of less than 10 years due to co-morbid conditions in the opinion of the investigator.
- •Known results from most recent lab studies obtained as part of routine care prior to study entry showing ANY of the following values:
- •ANC (absolute neutrophil count) less than 1200/mm3;
- •Platelet count less than 100,000/mm3;
- •Hemoglobin less than 10 g/dL;
- •Total bilirubin greater than ULN (upper limit of normal) for the lab or greater than 1.5 x ULN for patients who have a bilirubin elevation due to Gilbert's disease or similar syndrome involving slow conjugation of bilirubin;
研究组 & 干预措施
Arm 1: Ovarian Function Suppression + Aromatase Inhibitor
Aromatase inhibitor co-administered with a GnRH agonist (gonadotropin releasing hormone) for 5 years. The choice of AI is per investigator discretion. The choice of GnRH agonist and dosing schedule is per investigator's discretion. Options commonly include goserelin, leuprolide, or triptorelin given monthly or every-three-months. The dose and schedule of AI should be consistent with the drug package insert. Endocrine treatment beyond 5 years is at the investigator's discretion. Bilateral oophorectomy may substitute for ovarian suppression if desired.
干预措施: Ovarian Function Suppression + Aromatase Inhibitor
Arm 2 Adjuvant Chemotherapy + Ovarian Function Suppression + Aromatase Inhibitor
Adjuvant chemotherapy of investigator's choice followed by an aromatase inhibitor (AI) co-administered with an GnRH agonist for 5 years. The choice of AI is per investigator discretion. The choice of GnRH agonist and dosing schedule is per investigator's discretion. Options commonly include goserelin, leuprolide, or triptorelin given monthly or every-three-months. The dose and schedule of AI should be consistent with the drug package insert. Endocrine treatment beyond 5 years is at the investigator's discretion. Bilateral oophorectomy may substitute for ovarian suppression if desired.
干预措施: Ovarian Function Suppression + Aromatase Inhibitor
Arm 2 Adjuvant Chemotherapy + Ovarian Function Suppression + Aromatase Inhibitor
Adjuvant chemotherapy of investigator's choice followed by an aromatase inhibitor (AI) co-administered with an GnRH agonist for 5 years. The choice of AI is per investigator discretion. The choice of GnRH agonist and dosing schedule is per investigator's discretion. Options commonly include goserelin, leuprolide, or triptorelin given monthly or every-three-months. The dose and schedule of AI should be consistent with the drug package insert. Endocrine treatment beyond 5 years is at the investigator's discretion. Bilateral oophorectomy may substitute for ovarian suppression if desired.
干预措施: Adjuvant Chemotherapy + Ovarian Function Suppression
结局指标
主要结局
Invasive breast cancer-free survival (IBCFS)
时间窗: Time from randomization for duration of trial, 11 years
Time from randomization to the first diagnosis of local invasive recurrence following mastectomy, local invasive recurrence in the ipsilateral breast following lumpectomy, regional recurrence, distant recurrence, contralateral invasive breast cancer, or death from any cause prior to recurrence or contralateral breast cancer.
次要结局
- Invasive disease-free survival (IDFS)(Time from randomization for duration of trial, 11 years)
- Distant recurrence-free interval (DRFI)(Time from randomization for duration of trial, 11 years)
- Breast cancer-free interval (BCFI)(Time from randomization for duration of trial, 11 years)
- Menopausal symptoms measured by the FACT ESS-19 score(Measured at one year after randomization)
- Pain during aromatase inhibitor (AI) therapy(Measured at one year after randomization)
- Overall survival(Time from randomization for duration of trial, 11 years)