Capecitabine in Combination With Aromatase Inhibitor Versus Aromatase Inhibitors, in Hormonal Receptor Positive Recurrent or Metastatic Breast Cancer Patients, Randomized Controlled Study (CONCEPT Trial)
试验速览
- 阶段
- 2 期
- 入组人数
- 124
- 试验地点
- 1
- 主要终点
- Progress-free survival
研究概览
简要总结
Women with recurrent or metastatic breast cancer who are hormone receptor positive are candidates for first line hormonal therapy including aromatase inhibitors. In the past few years new combination therapies became available as fulvastrant or palbociclib with letrezole; increasing the progression free survival (PFS). A retrospective study showed that combination of capecitabine with aromatase inhibitors increase PFS as 1st and 2nd line line treatment another prospective study showed the same results. The aim of our study is confirm such data by a randomized controlled trial.
详细描述
Breast cancer is the most commonly diagnosed cancer and the leading cause of cancer death among women worldwide, accounting for 25% of total cancer cases (Globocan, 2012) It ranks as the most prevalent cancer among women in the Middle East and Northern Africa (Ferlay et al., 2015). In Egypt, breast cancer is the most common type of cancer among females (Ibrahim et al., 2014).
Survival of breast cancer patients depends on the disease stage. Most of the patients with localized disease experience long-term disease-free survival. Meanwhile, those who develop metastasis have a 5-year relative survival of only 24% (Siegel et al, 2015). Hormonal receptor positive (HR +ve) represent the most common subset (almost 70%) in both early and advanced disease (Clarke et al., 2012).
It is crucial to determine the menopausal status before initiation of treatment. For HR +ve / Her 2-negative metastatic breast cancer patients who premenopausal; If the patient had Disease free survival (DFS) of 12 months or more, or if she was diagnosed with metastasis de novo, the recommended first line is either ovarian ablation plus tamoxifen or aromatase inhibitor (Cardoso et al., 2017). For postmenopausal patients aromatase inhibitors are recommended with median progression-free survival (PFS) between 8 and 10 months (Bonneterre et al., 2000) and 10 months (Paridaens et al., 2008).
Chemotherapy regimens that are prescribed in hormone receptor-positive patients includes microtubule inhibitors (including taxanes and vinca alkaloids), anthracyclines, gemcitabine, cyclophosphamide and capecitabine. But endocrinal therapy is preferred as long as the patient is not in visceral crisis (Cardoso et al., 2017).
Recently new drugs that increased progression free survival (PFS) has been approved in the treatment of HR +ve metastatic breast cancer (MBC) as fulvastrant (Selective estrogen receptor modulator) (Ellis et al., 2015) and palbocilib (Ck4/6 inhibitor) (Finn et al., 2015) as first line and eveirolimus (mTor inhibitor)(Pritchard et al., 2012) as second line.
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
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Adult women with locoregionally recurrent or metastatic disease not amenable to curative therapy
- •Eastern Cooperative Oncology Group (ECOG) 0-2
- •Hormone receptor positive
- •No prior systemic anti-cancer therapy for advanced ER+ disease ( hormonal therapy)
- •Measurable disease defined by revised RECIST criteria (version 1.1), or bone-only disease
- •normal laboratory values
- •Postmenopausal or premenopausal with oophorectomy (medical or surgical).
排除标准
- •Patients with advanced, symptomatic, visceral spread that are at risk of life threatening complication in the short term
- •Prior (neo) adjuvant treatment with same aromatase inhibitor type with DFI =< 12 months from completion of treatment.
- •Known uncontrolled or symptomatic central nervous system metastases
- •Second primary malignancy
- •Serious uncontrolled intercurrent infections or intercurrent medical or psychiatric illness
- •unable to swallow tablets, or malabsorption patients.
- •unwilling or unable to comply with study protocol or unable to meet the follow up.
- •patients who researchers considered were not suitable to participate.
研究组 & 干预措施
A.I. + Capeciabine
Patients will receive Capecitabine 625 mg/m2 bid PO for 14 days to be repeated every 21 days until progression in combination with aromatase inhibitor if postmenopausal, addition of LHRH agonist will be added if premenopausal.
干预措施: Capecitabine plus aromatase inhibitor (Drug)
A.I
Patients will receive aromatase inhibitors ( letrozole 2.5 mg PO per day or Anastrozole 1 mg PO per day or aromasin 25 mg PO per day) if post-menopausal, if premenopausal leutnising hormone releasing hormone (LHRH) agonist will be added to the aromatase inhibitor.
干预措施: A.I. (Drug)
结局指标
主要结局
Progress-free survival
时间窗: up to 24 months
Time from randomization to the first documentation of objective tumor progression or to death due to any cause or Intolerable toxicity.
次要结局
- Adverse events(till progression or up to 24 months whichever earlier)
研究者
Hesham Elghazaly,MD
professor
Ain Shams University