Influence of Exceptional Patient Characteristics on Everolimus Exposure
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 56
- 试验地点
- 7
- 主要终点
- everolimus AUC
研究概览
简要总结
A study to determine whether everolimus pharmacokinetics in elderly and obese patients is different compared to control patients.
Furthermore the investigators will investigate the relation between metabolic response assessed with [18F] Fluorodeoxyglucose-Positron Emission Tomography (FDG-PET) and everolimus exposure and clinical benefit.
The investigators will explore whether dose escalation in patients who are hypothetically underexposed will result in an increase in metabolic response.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Diagnostic
- 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 metastatic or locally advanced breast cancer not amenable to curative treatment by surgery or radiotherapy.
- •Histological or cytological confirmation of estrogen-receptor positive (ER+) breast cancer
- •Postmenopausal women
- •Radiological or clinical evidence of recurrence or progression on last systemic therapy prior to enrollment.
- •Progression following a non-steroidal aromatase inhibitor
- •Falling into one of the following categories
- •elderly patients (age ≥ 70 years and BMI < 30 kg/m2); or
- •obese patients (BMI ≥ 30 kg/m2 and age < 70 years); or
- •control patients (BMI < 30 kg/m2 and age < 70 years);
- •Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 5 x ULN
- •Adequate renal function: calculated creatinine clearance, as estimated by GFR using the MDRD formula, is ≥ 30ml/min/1.73m2
- •Performance status ECOG 0 - 2 (Karnofsky index: 60 - 100)
- •Patient is willing and able to sign the Informed Consent Form prior to screening evaluations
排除标准
- •Patients aged ≥ 70 years AND BMI ≥ 30 kg/m2
- •HER2-overexpressing patients by local laboratory testing (IHC 3+ staining or in situ hybridization positive).
- •Previous treatment with exemestane or mTOR inhibitors. Except for the treatment with exemestane in the adjuvant setting.
- •Known hypersensitivity to mTOR inhibitors, e.g. sirolimus (rapamycin).
- •Patients with a known history of HIV seropositivity.
- •Any severe and / or uncontrolled medical conditions such as:
- •Unstable angina pectoris, serious uncontrolled cardiac arrhythmia
- •Patients with severe hepatic impairment (Child-Pugh A/B/C)
- •Uncontrolled diabetes mellitus
- •Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of study drugs (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome)
- •Patients who test positive for hepatitis B or C
- •Patients being treated with drugs recognized as being strong inhibitors or inducers of the isoenzyme CYP3A within the last 5 days prior to enrollment
- •History of non-compliance to medical regimens
- •Patients unwilling to or unable to comply with the protocol
研究组 & 干预措施
everolimus dose escalation
patients with an AUC below mean will have dose escalation of everolimus based on their AUC
干预措施: everolimus dose escalation (Drug)
结局指标
主要结局
everolimus AUC
时间窗: day 14 after start treatment
The primary aim is to show a difference in everolimus exposure (AUC0-24hr) of at least 25% in elderly patients (≥70 years) and obese patients (BMI ≥ 30 kg/m2) compared to the control group (≤ 70 years; BMI ≤ 30 kg/m2), after reaching steady state everolimus pharmacokinetics (day 14, but at least after 7 days of everolimus therapy).
次要结局
- correlation between early metabolic response and PFS(within 90 days after start of treatment)
- correlation between early metabolic response and AUC(15 days after start of treatment)
- effect dose escalation on metabolic respons(within 36 days after start of treatment)
- correlation between AUC and frequency of adverse event(4 months after start of treatment)