Randomized Trial to Assess the Benefit of Adding Trastuzumab to Capecitabine and Vinorelbine as Second Line for HER2positive Breast Cancer Patients With Locally Advanced or Metastatic Disease, Previously Treated With Trastuzumab and Taxanes
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 14
- 试验地点
- 1
- 主要终点
- Clinical benefit rate
研究概览
简要总结
Eligible patients must receive vinorelbine plus capecitabine, with or without trastuzumab, until disease progression or unbearable toxicity. Cycles will be administered every 3 weeks.Human epidermal growth factor receptor 2 (HER2) status must be locally assessed by immunohistochemistry (IHC). All 3+ patients are eligible. In 2+ patients, HER2 status must be confirmed by fluorescence in situ hybridization (FISH).
详细描述
Principal outcome is clinical benefit (complete + partial responses + stable disease). Sample size in each arm has been estimated with the Fleming method. Previous data show a clinical benefit rate of vinorelbine plus capecitabine around 50%. The researchers assume trastuzumab can increase it by 20%. With an alpha error of 0.05 and 80% power, 37 patients per arm are needed.
This is a randomised phase II trial. With a minimum expected benefit rate of 50%, at least 36 patients are needed to choose, with a 90% of probability to be right, the best treatment arm, providing it increases benefit rate at least by 15%.
Assuming a drop-out rate of 10%, the total number of patients needed is 82, 41 per treatment arm.
Patients will be stratified as per investigational site, and presence of visceral metastatic lesion (liver, lung, pleura, heart, peritoneum, suprarenal glands). All patients must receive 2 cycles. If no disease progression is detected, treatment must continue until progression or unbearable toxicity.
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 70 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Written informed consent.
- •Women older than 18 years old.
- •HER2 positive breast cancer with histological diagnoses.
- •Non-operable locally advanced or metastatic disease, previously treated with trastuzumab and taxanes.
- •Measurable or non-measurable disease as per Response Evaluation Criteria in Solid Tumors (RECIST).
- •Disease progression during or after treatment with trastuzumab and taxanes.
- •Maximum of 1 previous chemotherapy line for advanced or metastatic disease.
- •Previous radiotherapy is allowed if radiated area is not the only documented lesion.
- •At least 4 weeks since the last administration of antineoplastic treatment and all toxicities resolved.
- •Performance status Eastern Cooperative Oncology Group (ECOG) >=
- •Life expectancy of at least 12 weeks.
- •Left Ventricular Ejection Fraction (LVEF) evaluation (>=50%) in previous 4 weeks.
- •Hematology:
- •neutrophils >=1.5 x 10e9/l;
- •platelets >= 100 x 10e9/l;
- •hemoglobin >= 10 mg/dl
- •Hepatic function:
- •total bilirubin <= 1.5 x under normal limit (UNL);
- •Aspartate aminotransferase (SGOT) and Alanine aminotransferase (SGPT) and alkaline phosphatase <= 2.5 x UNL, or <=5 x UNL if hepatic lesions present
- •Renal function:
- •creatinine <= 175 µmol/l (2 mg/dl);
- •creatinine clearance >= 60 ml/min.
- •Patients able to comply with treatment and follow-up.
- •Negative pregnancy test in the previous 14 days. Adequate contraceptive method during treatment and up to 3 months after finalised.
- •Brain metastatic lesions are allowed provided all other criteria are met.
- •Male who met inclusion criteria are eligible.
排除标准
- •History of hypersensitivity to vinorelbine, trastuzumab, rat proteins or trastuzumab components.
- •History of dyspnea at rest, or chronic oxygen therapy required.
- •Active infection.
- •Second malignancy, except for cervical in situ carcinoma, basal skin carcinoma, adequately treated. Previous malignancies with a 5 year disease free survival are allowed.
- •Pregnant or lactating women.
- •Any other serious medical pathology, such as congestive heart failure, unstable angina, history of myocardial infarction during the previous year, uncontrolled hypertension or high risk arrhythmias.
- •History of neurological or psychiatric disorders, which could preclude the patients to free informed consent.
- •Active uncontrolled infection.
- •Active peptic ulcer, unstable diabetes mellitus.
- •Concomitant treatment with other investigational products. Participation in other clinical trials with a non-marketed drug in the 30 previous days before randomization.
- •Concomitant treatment with other therapy for cancer.
研究组 & 干预措施
Arm A: VX
Vinorelbine and capecitabine (VX): vinorelbine 25 mg/m2 iv, days 1 and 8 each cycle (21 days), followed of capecitabine 825 mg/m2, orally, twice a day, days 1-14 each cycle (21 days).
干预措施: Vinorelbine (Drug)
Arm A: VX
Vinorelbine and capecitabine (VX): vinorelbine 25 mg/m2 iv, days 1 and 8 each cycle (21 days), followed of capecitabine 825 mg/m2, orally, twice a day, days 1-14 each cycle (21 days).
干预措施: Capecitabine (Drug)
Arm B: VXH
Vinorelbine, capecitabine and trastuzumab (VXH): vinorelbine 25 mg/m2 iv, days 1 and 8 each cycle (21 days), followed of capecitabine 825 mg/m2, orally, twice a day, days 1-14 each cycle (21 days) and trastuzumab 4 mg/kg iv (loading dose first week), followed by 2 mg/kg weekly.
干预措施: Vinorelbine (Drug)
Arm B: VXH
Vinorelbine, capecitabine and trastuzumab (VXH): vinorelbine 25 mg/m2 iv, days 1 and 8 each cycle (21 days), followed of capecitabine 825 mg/m2, orally, twice a day, days 1-14 each cycle (21 days) and trastuzumab 4 mg/kg iv (loading dose first week), followed by 2 mg/kg weekly.
干预措施: Capecitabine (Drug)
Arm B: VXH
Vinorelbine, capecitabine and trastuzumab (VXH): vinorelbine 25 mg/m2 iv, days 1 and 8 each cycle (21 days), followed of capecitabine 825 mg/m2, orally, twice a day, days 1-14 each cycle (21 days) and trastuzumab 4 mg/kg iv (loading dose first week), followed by 2 mg/kg weekly.
干预措施: Trastuzumab (Drug)
结局指标
主要结局
Clinical benefit rate
时间窗: Through study completion, an average of 1 year
Clinical benefit rate is defined as the rate of objective responses (complete responses and partial responses to treatment) and stabilizations, with a minimum duration of 24 weeks.
次要结局
- Time to progression (TTP)(Through study completion, an average of 1 year)
- Objective Response Rate (ORR)(Through study completion, an average of 1 year)
- Response Duration (RD)(Through study completion, an average of 1 year)
- The Number of Participants Who Experienced Adverse Events (AE)(Through study completion, an average of 1 year)
- Overall Survival (OS)(Through study completion, an average of 1 year)