A Phase 1/2A Dose Escalation Study of LAM561 in Adult Patients With Advanced Solid Tumours Including Malignant Glioma
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 54
- 试验地点
- 5
- 主要终点
- Number of patients with adverse events
研究概览
简要总结
This is a phase 1/2A, open label, non-randomized study in patients with advanced solid tumours including malignant glioma
详细描述
This is an open label, non-randomized study in patients with advanced solid tumours including malignant glioma. The study will be performed in two phases - a dose escalation phase following a standard "3+3" design to establish dose-limiting toxicity (DLT) and a safe dose of LAM561 followed by two expanded safety cohorts (approximately 10 of whom have malignant glioma and approximately 10 of whom have other advanced solid tumours that are suitable for biopsy) treated at the maximum tolerated dose (MTD). If the MTD is well tolerated in the expanded safety cohorts, that dose becomes the recommended phase 2 dose (RP2D). During each dose cohort, at least one week must elapse between the first and subsequent patients receiving treatment with LAM561. Patients may receive palliative localized radiotherapy, if needed (however, this lesion cannot be a target lesion for evaluation of the treatment response).
Safety, pharmacokinetics (PK), pharmacodynamics and efficacy will be evaluated during the study at pre-defined timepoints
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Dose Cohort 1
Intervention: LAM561. 7 dose cohorts of up to 6 patients have been performed in the dose escalation phase. The starting dose cohort received 250 mg twice daily.
干预措施: LAM561 (Drug)
Dose Cohort 2
Intervention: LAM561. 500 mg twice daily
干预措施: LAM561 (Drug)
Dose Cohort 3
Intervention: LAM561.
1g twice daily
干预措施: LAM561 (Drug)
LAM561 Dose Cohort 4
Intervention: LAM561. 2g twice daily
干预措施: LAM561 (Drug)
LAM561 Dose Cohort 5
Intervention: LAM561. 4g twice daily
干预措施: LAM561 (Drug)
LAM561Dose Cohort 6
Intervention: LAM561. 4g three times daily
干预措施: LAM561 (Drug)
LAM561 Dose Cohort 7
Intervention: LAM561. 8g twice daily
干预措施: LAM561 (Drug)
LAM561 Dose Expansion cohort. Glioma
Intervention: LAM561 at the MTD: 4g three times daily. Up to 10 patients with malignant glioma.
干预措施: LAM561 (Drug)
LAM561 Dose Expansion cohort. Non-glioma
Intervention: LAM561 at the MTD: 4g three times daily. Up to 10 patients with other advanced solid tumours that are suitable for biopsy.
干预措施: LAM561 (Drug)
结局指标
主要结局
Number of patients with adverse events
时间窗: From the first dose of study drug until 30 days after the last dose of study drug
All adverse events will be recorded including clinically significant physical examinations and vital signs, laboratory safety tests and 12-lead electrocardiograms
次要结局
- Concentration of LAM561 in blood measured by LC-MS/MS(21 days)
- Concentration of micro RNA in blood(First 22 days then every 9 cycles until any criterion for discontinuation is met (clinical or radiological progression of disease, clinically unacceptable toxicity, or another "general" discontinuation criterion))
- Radiological disease progression(Every 6 weeks until any criterion for discontinuation is met (clinical or radiological progression of disease, clinically unacceptable toxicity, or another "general" discontinuation criterion))
- Concentration of biomarkers in blood or tumour tissue(First 22 days then every 9 cycles until any criterion for discontinuation is met (clinical or radiological progression of disease, clinically unacceptable toxicity, or another "general" discontinuation criterion))
- Clinical disease progression(until any criterion for discontinuation is met (clinical or radiological progression of disease, clinically unacceptable toxicity, or another "general" discontinuation criterion)