"A Randomized Multicenter Phase II Trial to Evaluate the Effectiveness of Selective Neoadjuvant Treatment According to Immunohistochemical Subtype for HER2 Negative Breast Cancer Patients"
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 189
- 试验地点
- 12
- 主要终点
- Pathological Response for Basal Group 2
研究概览
简要总结
This is an open-label study that includes two substudies of random distribution. First,a sample of the primary tumor will be obtained and will be analyzed by an immunohistochemical technique to determine several markers.Depending on the expression of these markers, the patients will be characterize as group 1 (Luminal A phenotype) or group 2 (Basal phenotype) and a random assignment will be performed to standard or experimental treatment.
详细描述
Group 1 (Luminal A):
- Standard treatment: Epirubicin (E) 90 mg/ m2 intravenous (iv) in combination with Cyclophosphamide (C) 600 mg/ m2 iv every 21 days for 4 cycles, followed by docetaxel (D)100 mg/m2 iv every 21 days for 4 cycles.
EC x 4 -> D x 4
- Selective treatment: Postmenopausal patients: exemestane x 6 months; Premenopausal patients: goserelin x 6 months + exemestane x 6 months
Group 2 (Basal):
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
- •Written informed consent.
- •Breast cancer with histological diagnosis.
- •Negative Human Epidermal Growth Factor Receptor 2 (HER2) tumours defined as immunohistochemistry (IHQ) 0,1+.
- •No evidence of suspicion of metastatic disease.
- •Age >= 18 years old.
- •Performance status (Karnofsky index) >= 80 (ECOG 0,1).
- •Adequate cardiac function by ECG in the previous 12 weeks.
- •Hematology: neutrophils >= 1,5 x10^9/l; platelets >= 100 x10^9/l; hemoglobin >= 10 g/dl.
- •Adequate hepatic function: total bilirubin <= 1x Upper Normal Limit (UNL); Aspartate aminotransferase (AST) (SGOT) and Alanine aminotransferase (ALT) (SGPT) <= 2.5 x UNL; alkaline phosphatase <= 2.5 x UNL.
- •Adequate renal function: creatinine <= 1 x UNL; creatinine clearance >= 60 ml/min.
- •Patients able to comply with study treatment and follow-up.
- •Negative pregnancy test in the previous 14 days.
排除标准
- •HER2 positive tumours (defined as IHQ 3+ or positive fluorescence in situ hybridization [FISH]).
- •Prior systemic therapy for breast cancer (immunotherapy, hormonotherapy, chemotherapy).
- •Prior treatment with anthracyclines or taxanes (paclitaxel, docetaxel) for any previous malignancy.
- •Prior radiotherapy for breast cancer.
- •Bilateral invasive breast cancer.
- •Pregnant or lactating women.
- •Previous grade >= 2 motor or sensorial neurotoxicity (National Cancer Institute Common Toxicity Criteria [NCICTC]).
- •Other serious comorbidities: congestive heart failure or unstable angina; prior history of myocardial infarction in previous year; uncontrolled hypertension (HT); high risk arrhythmias; history of significant neurological or psychiatric disorders; uncontrolled active infection; active peptic ulcer; unstable diabetes mellitus; dyspnea at rest; or chronic therapy with oxygen.
- •Previous or current history of neoplasms different from breast cancer, except for skin carcinoma, cervical in situ carcinoma, or any other tumor curatively treated and without recurrence in the last 10 years; ductal in situ carcinoma in the same breast; lobular in situ carcinoma.
- •Chronic treatment with corticosteroids.
- •Contraindications for administration of corticosteroids.
- •Concomitant treatment with other therapy for cancer.
研究组 & 干预措施
Group 1 (Luminal A) Standard treatment
Standard treatment: Epirubicin (E) 90 mg/ m2 intravenous (iv) in combination with Cyclophosphamide (C) 600 mg/ m2 iv every 21 days for 4 cycles, followed by docetaxel (D)100 mg/m2 iv every 21 days for 4 cycles.
干预措施: Epirubicin (Drug)
Group 1 (Luminal A) Standard treatment
Standard treatment: Epirubicin (E) 90 mg/ m2 intravenous (iv) in combination with Cyclophosphamide (C) 600 mg/ m2 iv every 21 days for 4 cycles, followed by docetaxel (D)100 mg/m2 iv every 21 days for 4 cycles.
干预措施: Cyclophosphamide (Drug)
Group 1 (Luminal A) Standard treatment
Standard treatment: Epirubicin (E) 90 mg/ m2 intravenous (iv) in combination with Cyclophosphamide (C) 600 mg/ m2 iv every 21 days for 4 cycles, followed by docetaxel (D)100 mg/m2 iv every 21 days for 4 cycles.
干预措施: Docetaxel (Drug)
Group 1 (Luminal A) Selective treatment
Selective treatment:
Postmenopausal patients: exemestane x 6 months Premenopausal patients: goserelin x 6 months + exemestane x 6 months
干预措施: Exemestane (Drug)
Group 1 (Luminal A) Selective treatment
Selective treatment:
Postmenopausal patients: exemestane x 6 months Premenopausal patients: goserelin x 6 months + exemestane x 6 months
干预措施: Goserelin (Drug)
Group 2 (Basal) Standard treatment
Standard treatment: Epirubicin (E) 90 mg/ m2 intravenous (iv) in combination with Cyclophosphamide (C) 600 mg/ m2 iv every 21 days for 4 cycles, followed by docetaxel (D)100 mg/m2 iv every 21 days for 4 cycles.
干预措施: Epirubicin (Drug)
Group 2 (Basal) Standard treatment
Standard treatment: Epirubicin (E) 90 mg/ m2 intravenous (iv) in combination with Cyclophosphamide (C) 600 mg/ m2 iv every 21 days for 4 cycles, followed by docetaxel (D)100 mg/m2 iv every 21 days for 4 cycles.
干预措施: Cyclophosphamide (Drug)
Group 2 (Basal) Standard treatment
Standard treatment: Epirubicin (E) 90 mg/ m2 intravenous (iv) in combination with Cyclophosphamide (C) 600 mg/ m2 iv every 21 days for 4 cycles, followed by docetaxel (D)100 mg/m2 iv every 21 days for 4 cycles.
干预措施: Docetaxel (Drug)
Group 2 (Basal) Selective treatment
Selective treatment: Epirubicin (E) 90 mg/ m2 intravenous (iv) in combination with Cyclophosphamide (C) 600 mg/ m2 iv every 21 days for 4 cycles, followed by docetaxel (D)100 mg/m2 iv and carboplatin (Cb) (area under the curve = 6 mg/mL) iv every 21 days for 4 cycles.
干预措施: Epirubicin (Drug)
Group 2 (Basal) Selective treatment
Selective treatment: Epirubicin (E) 90 mg/ m2 intravenous (iv) in combination with Cyclophosphamide (C) 600 mg/ m2 iv every 21 days for 4 cycles, followed by docetaxel (D)100 mg/m2 iv and carboplatin (Cb) (area under the curve = 6 mg/mL) iv every 21 days for 4 cycles.
干预措施: Cyclophosphamide (Drug)
Group 2 (Basal) Selective treatment
Selective treatment: Epirubicin (E) 90 mg/ m2 intravenous (iv) in combination with Cyclophosphamide (C) 600 mg/ m2 iv every 21 days for 4 cycles, followed by docetaxel (D)100 mg/m2 iv and carboplatin (Cb) (area under the curve = 6 mg/mL) iv every 21 days for 4 cycles.
干预措施: Docetaxel (Drug)
Group 2 (Basal) Selective treatment
Selective treatment: Epirubicin (E) 90 mg/ m2 intravenous (iv) in combination with Cyclophosphamide (C) 600 mg/ m2 iv every 21 days for 4 cycles, followed by docetaxel (D)100 mg/m2 iv and carboplatin (Cb) (area under the curve = 6 mg/mL) iv every 21 days for 4 cycles.
干预措施: Carboplatin (Drug)
结局指标
主要结局
Pathological Response for Basal Group 2
时间窗: Up to 24 weeks
This primary outcome only applies for the basal group 2 as per protocol. The pathological response in luminal group 1 was not pre-specified even as a Secondary Outcome. Pathological response was assessed after surgery, according to the Miller \& Payne criteria, which stratifies the responses based on the proportion of remaining tumor and post-chemotherapy changes, evaluating separately the response in breast and axilla. Grades 1-4 are categorised as a partial pathological response (pPR) and grade 5 was a complete pathological response (cPR).
次要结局
- Breast Conservative Surgery Rate(Up to 24 weeks)
- Axillary Node Status at the Time of Surgery(Up to 24 weeks)
- Clinical Response Rate(Up to week 24)