A Randomized, Multicentre, Open-Label, Phase III Study of Lapatinib Plus Capecitabine Versus Trastuzumab Plus Capecitabine in Patients With Anthracycline- or Taxane-Exposed ErbB2-Positive Metastatic Breast Cancer
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 540
- 试验地点
- 1
- 主要终点
- Number of Participants With Central Nervous System (CNS) Metastases (as Assessed by Independent Review) as the Site of First Relapse
研究概览
简要总结
This open label study was designed to evaluate Lapatinib effect on incidence of brain metastases in ErbB2 (HER2) positive metastatic breast cancer patients exposed to prior taxanes or anthracyclines.
详细描述
The study was terminated based on the IDMC recommendation in 2012, collection of efficacy outcome measures was discontinued and all primary and secondary outcome measures were reported in 2012.
An amendment protocol allowed subjects who were on study treatment to enroll in a Long Term Follow Up (LTFU) phase if they had evidence of clinical benefit but no local access to standard of care treatments. Subjects received study treatment until disease progression, unacceptable toxicity, or subject withdrawal. In LTFU only Adverse Events data were collected. For the LTFU the Outcome Measure "Number of participants with the indicated Grade 3 or Grade 4 Adverse Events (AEs) occurring in >=2% of participants in either treatment arm" and "Adverse Events" were updated.
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
- •Females at least 18 years old;
- •ECOG Performance Status 0-2;
- •Histologically or cytologically confirmed HER2-positive invasive breast cancer, with Stage IV disease;
- •Prior treatment with taxanes or anthracyclines is required;
- •Prior treatment with other chemotherapeutic agents, trastuzumab, endocrine and radiation therapy is permitted;
- •Baseline LVEF ≥ 50% and not lower than the institutional lower limit of normal;
- •Concurrent treatment with bisphosphonates is permitted, however treatment must be initiated prior to the first dose of study therapy;
- •Able to swallow and retain oral medications;
- •Women with potential to have children must be willing to practice acceptable methods of birth control during the study;
- •Normal organ and marrow function.
排除标准
- •History and/or current evidence of CNS metastases. Baseline MRI scan by Independent Reviewer to confirm no brain mets;
- •Concurrent treatment with an investigational agent or participation in another treatment clinical trial;
- •Prior therapy with lapatinib or an ErbB2 inhibitor other than trastuzumab (including but not limited to trastuzumab-DM1 and neratinib) and capecitabine;
- •Known DPD deficiency;
- •Concurrent chemotherapy, radiation therapy, immunotherapy, biologic therapy, or hormonal therapy for treatment of cancer;
- •History of allergic reactions attributed to compounds chemically related to lapatinib (quinazolines), capecitabine, fluorouracil or any excipients;
- •Concomitant use of CYP3A4 inhibitors or inducers;
- •Malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel;
- •History of immediate or delayed hypersensitivity reaction to gadolinium contrast agents, or other contraindication to gadolinium contrast and other known contraindication to MRI;
- •Concurrent disease or condition that would make the subject inappropriate for study participation or any serious medical or psychiatric disorder that would interfere with the patient's safety or compliance to study procedures;
- •have acute or currently active/requiring anti-viral therapy hepatic or biliary disease (with exception of patients with Gilbert's syndrome, asymptomatic gallstones, liver metastases or stable chronic liver disease);
- •Any on-going toxicity from prior anti cancer therapy except alopecia;
- •Active cardiac disease;
- •Uncontrolled infection;
- •History of other malignancy, unless curatively treated with no evidence of disease for at least 5 years, subjects with adequately treated DCIS or LCIS, adequately treated non-melanoma skin cancer or curatively treated in-situ cancer of the cervix are eligible;
- •Used an investigational drug within 30 days or 5 half-lives, whichever is longer, preceding the first dose of protocol treatment;
- •Pregnant or lactating females.
研究组 & 干预措施
Lapatinib plus capecitabine
Lapatinib 1250 mg once daily and capecitabine 2000mg/m2/day, days 1-14, every 21 days
干预措施: capecitabine (Drug)
Lapatinib plus capecitabine
Lapatinib 1250 mg once daily and capecitabine 2000mg/m2/day, days 1-14, every 21 days
干预措施: lapatinib (Drug)
Trastuzumab plus capecitabine
trastuzumab loading dose of 8mg/kg followed by 6mg/kg q3weekly infusions, and capecitabine 2500mg/m2/day, days 1-14, every 21 days
干预措施: capecitabine (Drug)
Trastuzumab plus capecitabine
trastuzumab loading dose of 8mg/kg followed by 6mg/kg q3weekly infusions, and capecitabine 2500mg/m2/day, days 1-14, every 21 days
干预措施: trastuzumab (Drug)
结局指标
主要结局
Number of Participants With Central Nervous System (CNS) Metastases (as Assessed by Independent Review) as the Site of First Relapse
时间窗: From randomization until disease progression, death, or discontinuation from the study (average of 10 months). Cut-off 11-Jun-2012
CNS relapse is defined as the appearance of \>=1 enhancing lesion measuring \>=6 millimeters (mm) on T1Weighted (T1W) Magnetic Resonance Imaging (MRI) without CNS symptoms that were considered to be unequivocal based on all relevant radiological features (e.g., associated T2W signal abnormality); the appearance of any enhancing lesion on T1W MRI with CNS symptoms; unequivocal finding of leptomeningeal disease (defined as the dissemination of cancer throughout the spinal fluid), with or without symptoms; and unequivocal finding of multifocal intraparenchymal lesions with or without symptoms. In the event of the appearance of a \<6 mm lesions(s) without CNS lesions, or equivocal findings potentially suggesting leptomeningeal disease, these findings were followed with a subsequent scan within 6 weeks. If unequivocal progression was determined with the subsequent scan and/or CNS symptoms occurred, then CNS relapse crieria were met.
次要结局
- Number of Participants With CNS Progression at Any Time(From the time of randomization until death due to any cause (average of 10 months). Cut-off 11-Jun-2012)
- Number of Participants With Qualitative and Quantitative Toxicities(From the first dose of study medication until 30 days after the last dose of study treatment (average of 10 months))
- Number of Participants Expressing Glucocorticoid Receptor, Phosphatase and Tensin Homolog (PTEN), Phosphatidylinositide 3-kinase (PI3K)/AKT, Protein 53 (P53), Insulin-like Growth Factor-1 (IGF-1), and Genes Involved in Cell Cycle Regulation(Baseline)
- Number of Participants With the Indicated Grade 3 or Grade 4 Adverse Events (AEs) Occurring in >=2% of Participants in Either Treatment Arm(From the first dose of study medication until 30 days after the last dose of study treatment (average of 10 months).)
- Number of Participants With Overall Response (OR), as Assessed by the Investigator(From randomization until disease progression, death, or discontinuation from the study (average of 10 months). Cut-off 11-Jun-2012)
- Number of Participants With Clinical Benefit (CB)(From randomization until disease progression, death, or discontinuation from the study (average of 10 months). Cut-off 11-Jun-2012)
- Duration of Response(From the time of the first documented confirmed complete or partial response until disease progression or death, if sooner (average of 10 months). Cut-off 11-Jun-2012)
- Progression Free Survival (PFS), as Assessed by the Investigator(From randomization until disease progression, death, or discontinuation from the study (average of 10 months). Cut-off 11-Jun-2012)
- Time to First CNS Progression, Defined as the Time From Randomization Until the Date of Documented CNS Progression as the First Site of Relapse(From randomization until the date of documented CNS progression (average of 10 months). Cut-off 11-Jun-2012)
- Overall Survival(From randomization until death due to any cause (average of 10 months). Cut-off 11-Jun-2012)