MINDACT (Microarray In Node-Negative and 1 to 3 Positive Lymph Node Disease May Avoid Chemotherapy): A Prospective, Randomized Study Comparing the 70-Gene Signature With the Common Clinical-Pathological Criteria in Selecting Patients for Adjuvant Chemotherapy in Breast Cancer With 0 to 3 Positive Nodes
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 6,600
- 试验地点
- 1
- 主要终点
- Distant metastasis-free survival at 5 years
研究概览
简要总结
RATIONALE: Drugs used in chemotherapy work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells. Estrogen can cause the growth of breast cancer cells. Hormone therapy using tamoxifen may fight breast cancer by blocking the use of estrogen by the tumor cells. Letrozole may fight breast cancer by lowering the amount of estrogen the body makes. Giving chemotherapy and hormone therapy after surgery may kill any tumor cells that remain after surgery. It is not yet known whether genetic testing is more effective than clinical assessment in determining the need for chemotherapy in treating breast cancer.
PURPOSE: This randomized phase III trial is studying genetic testing to see how well it works compared with clinical assessment in determining the need for chemotherapy in women with breast cancer that is either node-negative or involves no more than 3 lymph nodes.
详细描述
OBJECTIVES:
Primary
- Compare a molecular profiling approach (70-gene signature) vs usual clinical assessment in assigning adequate risk categories (and the need to receive adjuvant chemotherapy or not) to breast cancer patients with 0-3 positive lymph nodes.
- Compare the efficacy and long-term toxicities of docetaxel and capecitabine vs standard anthracycline-based chemotherapy regimens in these patients.
- Determine the best endocrine treatment strategy (i.e., letrozole for 7 years vs sequential tamoxifen for 2 years followed by letrozole for 5 years) in these patients.
Secondary
- Compare both relative (hazard ratio) and absolute (percentage at 5 years) efficacy of these regimens, in terms of disease-free survival (DFS), distant metastasis-free survival (DMFS), and overall survival (OS), in these patients.
- Determine overall estimates of efficacy (DFS, DMFS, OS) for each treatment strategy according to clinical-pathological prognosis and molecular prognosis in these patients.
- Estimate the percentage of patients receiving chemotherapy per each prognostic method.
- Identify predictive gene expression profiles of clinical response/resistance to anthracycline-based and docetaxel-capecitabine chemotherapy in these patients.
- Compare novel gene expression signatures predicting clinical response in patients treated with sequential tamoxifen-letrozole vs letrozole alone.
- Compare the OS distributions in patients treated with these regimens.
- Compare the early and late toxicities of these regimens in these patients.
- Evaluate adjuvant endocrine treatment success or failure in the subgroup of postmenopausal patients with endocrine-responsive disease.
- Compare the safety profile of these two endocrine therapy regimens in these patients.
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 120 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Chemotherapy randomization: Arm I (anthracycline-based)
- FEC 100
- Canadian CEF
- CAF
- FAC
- E-CMF
干预措施: anthracycline-based (Drug)
Treatment decision randomization: Arm II
chemotherapy-decision-making according to genomic prognosis using the 70-gene signature
干预措施: docetaxel and capecitabine (Drug)
Chemotherapy randomization: Arm II (docetaxel and capecitabine)
- Docetaxel
- Capecitabine
干预措施: docetaxel and capecitabine (Drug)
Endocrine therapy randomization: Arm I
2 years of tamoxifen followed by 5 years of letrozole
干预措施: tamoxifen (Drug)
Endocrine therapy randomization: Arm I
2 years of tamoxifen followed by 5 years of letrozole
干预措施: Letrozole (Drug)
Endocrine therapy randomization: Arm II
7 years of letrozole
干预措施: Letrozole (Drug)
Treatment decision randomization: Arm I
chemotherapy-decision-making according to clinical criteria (using Adjuvant! Online)
干预措施: anthracycline-based (Drug)
Treatment decision randomization: Arm I
chemotherapy-decision-making according to clinical criteria (using Adjuvant! Online)
干预措施: docetaxel and capecitabine (Drug)
Treatment decision randomization: Arm II
chemotherapy-decision-making according to genomic prognosis using the 70-gene signature
干预措施: anthracycline-based (Drug)
结局指标
主要结局
Distant metastasis-free survival at 5 years
时间窗: from enrollment/randomization
o The primary endpoint for chemotherapy versus no chemotherapy (R-T) is that the 5-year distant metastasis free survival (DMFS) of 92% will be tested (a one-sided test).
Disease-free survival (DFS)
时间窗: from enrollment/randomization
o The primary endpoint for the chemotherapy randomization (R-C) is disease free survival (DFS).
DFS
时间窗: from enrollment/randomization
The primary test for the endocrine randomization (R-E) is DFS.
次要结局
- Safety (early and late)(from registration)
- DFS at 5 years(from enrollment/randomization)
- DMFS at 5 years(from enrollment/randomization)
- Proportion of patients treated with chemotherapy based on clinical prognosis compared to 70-gene signature prognosis(from enrollment)
- Overall survival at 5 years(from enrollment/randomization)