Randomized Phase II Trial of Everolimus 5 mg vs 10 mg/Daily for Patients With Advanced Neuroendocrine Tumors
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 100
- 试验地点
- 1
- 主要终点
- Progression free survival rate at 12 months
研究概览
简要总结
Everolimus is approved in many countries to treat patients with advanced/metastatic well-differentiated neuroendocrine tumors (NET), providing median progression-free survival times of approximately 12 months across different types of NET. However, it is can cause severe adverse effects. Phase I trial demonstrated that a dose of 5mg/day/week was sufficient to inhibit cell proliferation by blocking the mTOR pathway.
This is a randomized, open-label, phase II near-equivalence clinical trial of oral everolimus 5 mg vs 10 mg oral/daily and continuously in patients with Grade 1 or Grade 2 metastatic NET, with tumor progression or intolerance to at least one line of treatment and with radiological disease progression within 6 months.
详细描述
Everolimus toxicity can also be serious, requiring hospital medical assistance. In a study with more than 100 Latin American patients led by our group, approximately 20% of patients with NET treated with everolimus 10mg/day had serious infections, such as pneumonia, abscesses, pyelonephritis, with 7% developing opportunistic infections, such as toxoplasmosis and pneumocystosis, requiring hospital admissions.
The rationale for testing 5mg/day comes from the results of phase I trials of everolimus, where a dose of 5mg/day was sufficient to inhibit cell proliferation by blocking the mTOR pathway.
Therefore, everolimus 5mg/day appears to have antitumor effects equivalent to 10mg/day, but it is less toxic than 10mg/day. Retrospective data from our center also suggest that 5mg is similar to 10mg/daily in terms of time to treatment failure in patients with advanced NETs (unpublished data).
Objectives:
- To evaluate whether everolimus at a dose of 5 mg/day may be as effective, but safer, as 10 mg/day in the treatment of patients with advanced NET.
- To compare progression-free survival and time to treatment failure between study arms
- To compare radiological response using RECIST v.1.1 criteria.
- To compare the frequency of grade > 1 toxicities using CTCAE v.5.0.
- To assess tolerability by measuring the frequency and intensity of adverse events measured by the CTCAE version 5.0 criteria and the need for temporary or permanent interruption of everolimus.
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
- 16 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histological confirmation of well-differentiated Grade 1/Grade 2 NET from gastrointestinal, pancreatic, pulmonary or unknown primary sites.
- •Metastatic or locally advanced and unresectable disease, measurable by images
- •Disease progression by RECIST 1.1 in the last 6 months assessed by local investigators
- •At least one previous line of systemic treatment (suspended for more than 3 weeks).
- •Eastern Cooperative Oncology Group (ECOG) 0-2 o Good organ function:
- •Hemoglobin > 8 g/dL
- •Neutrophils ≥ 1,500/mm³
- •Platelets > 90,000/mm³
- •Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) ≤ 2.5 x ULN [upper limit of normal] or ≤ 5 x ULN for patients with liver metastases
- •Bilirubin ≤ 1.5 x ULN, creatinine < 1.5 mg/dL
排除标准
- •Aggressive disease requiring cytotoxic therapy
- •Severe/uncontrolled comorbid conditions that deem participant unfit for everolimus therapy, as per investigators' judgement.
研究组 & 干预措施
Everolimus 5
oral everolimus 5 mg/daily continuously until progression or intolerance or consent withdrawal. dose reduction for toxicity is allowed.
干预措施: Everolimus 5 MG (Drug)
Everolimus 10
oral everolimus 10 mg/daily continuously until progression or intolerance or consent withdrawal. dose reduction for toxicity is allowed.
干预措施: Everolimus 5 MG (Drug)
结局指标
主要结局
Progression free survival rate at 12 months
时间窗: 12 months
Proportion of patients without radiological progression or death at 12 months from first day of everolimus
次要结局
- progression free survival(12 months)
- time to treatment failure(12 months)
研究者
Rachel Riechelmann
Dr
AC Camargo Cancer Center