Phase I Study of TAK-228 (MLN0128) in Combination With Metformin in Patients With Advanced Cancers
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 31
- 试验地点
- 1
- 主要终点
- Incidence of serious adverse events
研究概览
简要总结
This phase I trial studies the side effects and best dose of sapanisertib and metformin in treating patients with cancers that have spread to other parts of the body (advanced/metastatic), have come back (recurrent), or do not respond to treatment (refractory). Sapanisertib and metformin may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
详细描述
PRIMARY OBJECTIVES:
I. To evaluate the safety and tolerability and to determine maximum tolerated dose (MTD) of the combination of sapanisertib (TAK-228) with metformin in patients with advanced cancers refractory to standard therapy.
SECONDARY OBJECTIVES:
I. To assess the clinical tumor response of this combination. II. To characterize the pharmacokinetic (PK) profile of metformin and TAK-228.
OUTLINE: This is a dose escalation study.
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
- 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
Treatment (metformin, sapanisertib)
Patients receive metformin PO 1-3 times daily on days 1-42 and sapanisertib PO daily on days 15-42 of cycle 1. Patients then receive metformin PO daily and sapanisertib PO daily on days 1-28 of cycle 2 and beyond. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
干预措施: Laboratory Biomarker Analysis (Other)
Treatment (metformin, sapanisertib)
Patients receive metformin PO 1-3 times daily on days 1-42 and sapanisertib PO daily on days 15-42 of cycle 1. Patients then receive metformin PO daily and sapanisertib PO daily on days 1-28 of cycle 2 and beyond. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
干预措施: Metformin (Drug)
Treatment (metformin, sapanisertib)
Patients receive metformin PO 1-3 times daily on days 1-42 and sapanisertib PO daily on days 15-42 of cycle 1. Patients then receive metformin PO daily and sapanisertib PO daily on days 1-28 of cycle 2 and beyond. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
干预措施: Pharmacological Study (Other)
Treatment (metformin, sapanisertib)
Patients receive metformin PO 1-3 times daily on days 1-42 and sapanisertib PO daily on days 15-42 of cycle 1. Patients then receive metformin PO daily and sapanisertib PO daily on days 1-28 of cycle 2 and beyond. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
干预措施: Sapanisertib (Drug)
结局指标
主要结局
Incidence of serious adverse events
时间窗: Up to 4 years
Assessed by Common Terminology Criteria for Adverse Events version 4.0. Descriptive statistics will be provided on the grade and type of toxicity by dose level.
Clinical and laboratory values
时间窗: Up to 4 years
Wilcoxon's Signed-Rank Test and Fisher's exact test will be used. A mixed model accounting for patient effects will be used to analyze longitudinal data (including biomarker data) over time.
Vital sign measurements
时间窗: Up to 4 years
Wilcoxon's Signed-Rank Test and Fisher's exact test will be used. A mixed model accounting for patient effects will be used to analyze longitudinal data (including biomarker data) over time.
GI symptoms
时间窗: Up to 4 years
Wilcoxon's Signed-Rank Test and Fisher's exact test will be used. A mixed model accounting for patient effects will be used to analyze longitudinal data (including biomarker data) over time.
Incidence of neurotoxicity
时间窗: Up to 4 years
Descriptive statistics will be provided on the grade and type of toxicity by dose level.
次要结局
- The peak plasma concentration (Cmax)(Up to 4 years)
- The area under the plasma concentration-time curve (AUC)(Up to 4 years)
- Elimination half-life (t1/2)(Up to 4 years)
- Incidence and grade of adverse events(Up to 4 years)
- Incidence of dose limiting toxicities(Up to 4 years)
- Withdrawals from study due to adverse events(Up to 4 years)
- Change in treatment regimen due to adverse events(Up to 4 years)
- Death during study(Up to 4 years)
- Establishment of recommended phase 2 dosage(Up to 42 days)
- Best tumor responses by dose level(Up to 4 years)
- Overall survival by dose level(Up to 4 years)
- Progression free survival by dose level(Up to 4 years)