NCT02028364已完成2 期
Pet Imaging as a Biomarker of Everolimus Added Value in Hormone Refractory postmenopausaL Women
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 55
- 试验地点
- 5
- 主要终点
- PFS based on RECIST criteria 1.1.
研究概览
简要总结
This is a prospective, single arm trial in which patients with locally advanced or metastatic endocrine receptor positive and HER2 negative breast cancer refractory to non-steroidal aromatase inhibitors (NSAI) will receive Everolimus 10mg orally daily given in conjunction with exemestane 25mg orally daily until disease progression or treatment discontinuation for any other reasons. The main objectives are to evaluate if early metabolic response (MR) using FDG-PET/CT is associated with progression free survival (PFS) and overall survival (OS) in this population.
Tumour, metastatic lesions and blood samples will be collected during the treatment period in order to identify biomarkers predicting resistance to study treatment. Results will be correlated with the results of early FDG PET/CT data in order to better characterise the non-responders.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 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
- •Adult women (≥18 years of age) with locally advanced or metastatic breast cancer not amenable to curative treatment by surgery or radiotherapy.
- •Histological or cytological confirmation of estrogen-receptor positive (ER+), HER2 negative breast cancer.
- •Postmenopausal female defined as:
- •Age ≥55 years and one year or more of amenorrhoea
- •Age <55 years and one year or more of amenorrhoea, with an estradiol assay <20pg/ml
- •Surgical menopause with bilateral oophorectomy NOTE: Ovarian radiation or treatment with a luteinizing hormone-releasing hormone (LHRH) agonist (goserelin or leuprolide) is not permitted for induction of ovarian suppression.
- •Breast cancer that is refractory to non-steroidal aromatase inhibitors (NSAI) (i.e. anastrozole or letrozole) defined as:
- •Recurrence while on, or within 12 months of end of adjuvant treatment with anastrozole or letrozole; OR
- •Progression while on, or within one month of end of anastrozole or letrozole or treatment for locally advanced or metastatic breast cancer.
- •NOTE: Letrozole or anastrozole do not have to be the last treatment prior to enrolment.
- •FDG-PET measurable disease defined as: at least one target lesion fulfilling following criteria:
- •Size ≥1.5cm; AND
- •FDG-PET avid lesion with uptake above the background liver uptake as described below: i.e. with a marked accumulation of FDG, at least 1.5-fold greater than liver SUV mean + 2 SDs (in 3cm spherical ROI in normal right lobe of liver). If liver is abnormal, target lesion should have uptake > 2.0 x SUV mean of blood pool in 1cm diameter ROI in descending thoracic aorta)
- •The target lesion can be a bone metastasis if it fulfils the above mentioned criteria.
- •In the case the target lesion is a lymph node, the small axis should be ≥ 1.5cm.
- •Radiological or clinical evidence of recurrence or progression on last systemic therapy prior to enrolment.
- •Adequate bone marrow function as shown by:
- •Haemoglobin (HgB) ≥9.0 g/dL
- •ANC ≥1,500/mm3 (≥1.5 x 109/L)
- •Platelets ≥100,000/mm3 (≥100x 109/L)
- •Adequate liver function as shown by:
- •Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5xULN (or ≤5 if hepatic metastases are present)
- •Total serum bilirubin ≤1.5 x ULN (≤3 ULN for patients known to have Gilbert Syndrome)
- •Adequate renal function as shown by Serum creatinine ≤1.5 x ULN
- •Fasting serum cholesterol, triglycerides and glucose
- •Fasting serum cholesterol ≤300 mg/dL or 7.75 mmol/L
- •Fasting triglycerides ≤2.5 x ULN
- •Fasting glucose < 1.5 x ULN
- •Eastern Co-operative Oncology Group (ECOG) performance status ≤
- •Written and signed informed consent obtained before any trial related activity.
- •Availability of a FFPE core of primary breast tumor
- •Possibility to obtain the mandatory blood samples for the translational research studies.
- •For patients with accessible metastatic lesions, possibility to obtain the mandatory biopsy (FFPE and frozen) of a metastatic lesion
- •Exclusion criteria:
- •HER2-overexpressing patients by local laboratory testing (IHC 3+ staining or in situ hybridization positive).
- •Patients with only non-measurable lesions by FDG-PET/CT (e.g. pleural effusion, ascites etc.).
- •Symptomatic visceral disease for example liver, pulmonary metastases or lymphangitis carcinomatosis.
- •Known hypersensitivity to mTOR inhibitors, e.g. sirolimus (rapamycin).
- •Another malignancy within 5 years prior to enrolment, with the exception of adequately treated in-situ carcinoma of the cervix, uteri, basal or squamous cell carcinoma or non-melanomatous skin cancer.
- •Radiotherapy within four weeks prior to enrolment except in case of localized radiotherapy for analgesic purpose or for lytic lesions at risk of fracture, which can then be completed within two weeks prior to enrolment. Patients must have recovered from radiotherapy toxicities prior to enrolment.
- •Currently receiving hormone replacement therapy, unless discontinued prior to enrolment.
- •Symptomatic brain metastases or other central nervous system metastases which are not controlled by local treatments.
- •Patients receiving concomitant immunosuppressive agents or chronic corticosteroid use at the time of study entry except in cases outlined below:
- •Topical applications (e.g. rash)
- •Inhaled sprays (e.g. obstructive airways disease)
- •Eye drops
- •Local injections (e.g. intra-articular)
- •Stable low dose of corticosteroids for at least two weeks before enrolment
- •Patients with known HIV seropositivity. Screening for HIV infection at baseline is not required
- •Acute and chronic, active infectious disorders (except for Hepatitis B and Hepatitis C positive patients).
- 另有 10 项未显示
排除标准
- 未提供
研究组 & 干预措施
Everolimus given in conjunction with exemestane
Experimental
Everolimus 10mg orally daily given in conjunction with exemestane 25mg orally daily until disease progression or treatment discontinuation for any other reasons.
干预措施: Everolimus (Drug)
Everolimus given in conjunction with exemestane
Experimental
Everolimus 10mg orally daily given in conjunction with exemestane 25mg orally daily until disease progression or treatment discontinuation for any other reasons.
干预措施: Exemestane (Drug)
结局指标
主要结局
PFS based on RECIST criteria 1.1.
时间窗: 2.5 years from FPI
To evaluate if early metabolic response (MR) using FDG-PET/CT is associated with progression free survival (PFS) in ER+, HER2 negative ABC or MBC patients treated with exemestane plus everolimus.
次要结局
- Overall survival (OS)(2.5 years from first patient in)
- * Proportion of FDG-PET/CT metabolic non-responders/FDG-PET/CT metabolic responders * Estimate the most suitable second FDG-PET/CT time point (2 weeks versus 4 weeks after initiation of treatment).(Baseline, day 14, Day 28 and at progression)
- Biomarker Assessment(baseline, day 14, day 28, every 12 weeks and at progression)
研究者
研究点 (5)
Loading locations...
相似试验
已完成
2 期
Biomarker Trial of Everolimus in Patients With Advanced Renal Cell CarcinomaRenal CancerRenal Cell CarcinomaNCT00827359Beth Israel Deaconess Medical Center25
已完成
2 期
Everolimus Combined With Anti-estrogen Therapy in Hormone-Receptor-Positive HER-2 Negative Advanced Breast CancerBreast CancerNCT02291913SCRI Development Innovations, LLC48
已完成
2 期
Everolimus (RAD001) in Metastatic Transitional Cell Carcinoma of the UrotheliumMetastatic Transitional Cell CarcinomaBladder CancerNCT00805129Memorial Sloan Kettering Cancer Center46
已完成
1 期
Study of Everolimus, Pemetrexed, Carboplatin, and Bevacizumab to Treat Stage IV Lung CancerNon Small Cell Lung CancerNCT01700400Cancer Research and Biostatistics Clinical Trials Consortium13
已完成
不适用
Pilot Study of Neo-Adjuvant Everolimus to Treat Advanced Renal Cell Carcinoma - Analysis of BiomarkersCarcinoma, Renal CellNCT01107509St. Joseph's Healthcare Hamilton20