CTRI/2012/11/003101暂停3 期
A Phase III trial to compare the safety and efficacy of lapatinib plus trastuzumab plus an aromatase inhibitor (AI) versus trastuzumab plus an AI versus lapatinib plus an AI as first-line therapy in postmenopausal subjects with hormone receptor positive, HER2-positive metastatic breast cancer (MBC) who have received trastuzumab and endocrine therapy in the neo/adjuvant setting.
试验速览
- 阶段
- 3 期
- 状态
- 暂停
- 入组人数
- 525
- 试验地点
- 7
- 主要终点
- Demonstrate superiority of lapatinib/trastuzumab/AI combination (Treatment Group A) vs. trastuzumab/AI combination (Treatment Group B) for overall survival.
研究概览
简要总结
Breast cancer is the most common form of cancer and the second leading cause of cancer-related deaths (after lung cancer) in women. Despite significant improvements in early diagnosis, all patients withMBC, and up to 40% of patients receiving adjuvant endocrine therapy, progress and die from the disease, demonstrating a medical need for improved therapies.
The current protocol, EGF114299 is designed to demonstrate a benefit in overall survival (OS) provided by lapatinib in HR+/HER2-positive patients who have been previously exposed to neoadjuvant and/or adjuvant trastuzumab. It will also provide further data to understand the role of dual HER2 suppression in this patient population. This study will enroll post-menopausal women who have recurrent disease after neoadjuvant and/or adjuvant therapy including trastuzumab and endocrine therapy which is being undertaken as a postmarketing requirement with regulatory authorities.
研究设计
- 研究类型
- Interventional
- 分配方式
- Computer generated randomization
- 盲法
- Open Label
入排标准
- 年龄范围
- 18.00 Year(s) 至 99.00 Year(s)（—）
- 性别
- Female
入选标准
- •Signed written informed consent
- •Post-menopausal female subjects ≥18 years of age.
- •Post-menopausal as defined by any of the following: • Age > 60 years • Age ≥ 45 years with amenorrhea > 12 months with an intact uterus • Having undergone a bilateral oophorectomy or radiation castration with amenorrhea for at least 6 months • FSH and estradiol levels in postmenopausal range (utilizing ranges from the local laboratory facility).
- •In subjects who have previously been treated with an GnRH/LHRH analogue, the last injection must have been administered > 4 months prior to randomization and menses must not have restarted
- •Histologically confirmed Stage IV invasive breast cancer • Subjects may have either measurable or non-measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST 1.1) [Eisenhauer, 2009]
- •Tumors that are ER+ and/or PgR+ by local laboratory
- •Documentation of HER2 overexpression or gene amplification, in the invasive component of either the primary tumor or metastatic disease site as defined as: • 3+ by Immunohistochemistry (IHC) and/or • HER2/neu gene amplification by fluorescence, chromogenic or silver in situ hybridization [FISH, CISH or SISH; >6 HER2/neu gene copies per nucleus or a FISH, CISH or SISH test ratio (HER2 gene copies to chromosome 17 signals) of ≥2.0]
- •Subject must have received prior neoadjuvant and/or adjuvant trastuzumab
- •Subject must have received prior neoadjuvant and/or adjuvant endocrine therapy
- •Subjects who have a life expectancy of > 6 months as assessed by the treating investigator
- •Have baseline of Left Ventricular Ejection Fraction (LVEF) ≥50% measured by echocardiography (ECHO) or multi-gated acquisition scan (MUGA)
- •ECOG performance status of 0-1
- •All prior treatment related toxicities must be CTCAE (Version 4.0) ≤ Grade 1 [NCI, 2009] at the time of randomization
- •Completion of screening assessments
- •Adequate baseline organ function defined by.
排除标准
- •Deviations from exclusion criteria are not allowed because they can potentially jeopardize the scientific integrity of the study, regulatory acceptability or subject safety.
- •Therefore, adherence to the criteria as specified in the protocol is essential.
- •Subjects meeting any of the following criteria must not be enrolled in the study:
- •History of another malignancy.
- •Exception: Subjects who have been disease-free for 5 years, or subjects with a history of completely resected non-melanoma skin cancer or successfully treated in situ carcinoma are eligible.
- •Subjects with extensive symptomatic visceral disease including hepatic involvement and pulmonary lymphangitic spread of tumor, or the disease is considered by the investigator to be rapidly progressing or life threatening (subjects who are intended for chemotherapy)
- •Subjects who received prior chemotherapy, hormonal therapy, immunotherapy, biologic therapy, or anti-HER2 therapy for advanced or metastatic disease
- •Serious cardiac illness or medical condition including but not confined to: • Uncontrolled arrhythmias • Uncontrolled or symptomatic angina • History of congestive heart failure (CHF) • Documented myocardial infarction 6 months from study entry
- •Known history of, or clinical evidence of, central nervous system (CNS)metastases or leptomeningeal carcinomatosis
- •Current active hepatic or biliary disease (with exception of subjects with Gilberts syndrome, asymptomatic gallstones, liver metastases or stable chronic liver disease per investigator assessment)
- •Concurrent disease or condition that may interfere with study participation, or any serious medical disorder that would interfere with the subject’s safety (for example, active or uncontrolled infection or any psychiatric condition prohibiting understanding or rendering of informed consent)
- •Have any clinically significant gastrointestinal abnormalities that may alter absorption such as malabsorption syndrome or major resection of the stomach or bowels
- •Have a known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to any of the study agents or their excipients that, in the opinion of the Investigator or GSK medical monitor, contraindicates their participation
- •Any prohibited medication
- •Administration of an investigational drug within 30 days or 5 half-lives, whichever is longer, preceding the first dose of study treatment.
结局指标
主要结局
Demonstrate superiority of lapatinib/trastuzumab/AI combination (Treatment Group A) vs. trastuzumab/AI combination (Treatment Group B) for overall survival.
时间窗: Death.
次要结局
- To compare OS in Treatment Group B (trastuzumab/AI) vs. Treatment Group C (lapatinib/AI) and Treatment Group A (trastuzumab/lapatinib/AI) vs. Treatment Group C (lapatinib/AI)(Death.)
- To compare progression free survival (PFS) in Treatment Group A (lapatinib/trastuzumab/AI) vs. Treatment Group B (trastuzumab/AI) and Treatment Group C ( lapatinib/AI) vs. Treatment Group B (trastuzumab/AI)(Disease Progression)
- To compare overall response rate (complete or partial response), time to response, and duration of response in Treatment Group A (lapatinib/trastuzumab/AI) vs. Treatment Group B (trastuzumab/AI) and Treatment Group C (lapatinib/AI) vs. Treatment Group B (trastuzumab/AI)(Disease Progression)
- To compare clinical benefit (complete response, partial response, or stable disease for at least 6 months) in Treatment Group A (lapatinib/trastuzumab/AI) vs. Treatment Group B (trastuzumab/AI) and Treatment Group C (lapatinib/AI) vs. Treatment Group B (trastuzumab/AI)(Disease Progression)
- To evaluate the safety and tolerability of all three(treatment groups (lapatinib/trastuzumab/AI, trastuzumab/ AI, or lapatinib/AI))
- To compare Treatment Group A (lapatinib/trastuzumab/AI) vs. Treatment Group B (trastuzumab/AI) and Treatment Group C (lapatinib/AI) vs. Treatment Group B (trastuzumab/AI) with respect to change in quality of life (QoL) status relative to baseline.(Day 1 pre-dose, every 12 weeks, and at discontinuation of study treatment)
研究者
研究点 (7)
Loading locations...
相似试验
已完成
不适用
Are Text Message Reminders an Effective Intervention for Improving the Uptake of Breast Screening?Breast ScreeningNCT01977599Imperial College Healthcare NHS Trust2,240
终止
1 期
A Study of Allogenic Natural Killer Cells in Combination With Trastuzumab and Pertuzumab in Adult Patients With Refractory Metastatic Her2 Positive Breast Cancer. NK-ACT-BC_2020Breast NeoplasmsNCT05385705Vall d'Hebron Institute of Oncology2
招募中
不适用
Prophylactic Irradiation to the Contralateral Breast for BCAs PatientsBreast CancerNCT04960839Second Affiliated Hospital, School of Medicine, Zhejiang University323
招募中
3 期
A Study of the Addition of Metronomic Capecitabine to Standard Adjuvant Therapy in High Risk HER2+ BC paTientsBreast CancerNCT03561740Sun Yat-sen University794
进行中（未招募）
3 期
CONcurrent vs SEqueNTial Adjuvant Treatments in Early Breast CancerBreast CancerNCT02918084IRCCS Azienda Ospedaliera Universitaria San Martino - IST Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy1,000