A Pharmacodynamic Study of Sirolimus in Older Children and Adults With Advanced Solid Malignancies
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 56
- 试验地点
- 1
- 主要终点
- Change in fasting glucose and fasting triglycerides
研究概览
简要总结
This clinical trial studies sirolimus in treating patients with solid tumors that are metastatic or cannot be removed by surgery. Sirolimus 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 describe the magnitude, inter-individual variability and time course of sirolimus-induced changes in fasting serum glucose and triglycerides.
SECONDARY OBJECTIVES:
I. To assess candidate genetic variants for their correlation with changes in fasting glucose and/or triglycerides.
II. To assess tumor response by the Response Evaluation Criteria In Solid Tumors (RECIST, version 1.1) and explore whether there is any correlation between response and changes in fasting glucose and/or triglycerides.
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
- 12 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically or cytologically confirmed solid tumor that is metastatic or unresectable and for which standard curative or palliative measures do not exist or are no longer effective
- •Weight >= 40 kg
- •Eastern Cooperative Oncology Group (ECOG) performance status =< 1
- •Life expectancy > 3 months
- •Absolute neutrophil count (ANC) >= l500/ul
- •Hemoglobin >= 9g/dL
- •Platelets >= 100,000/ ul
- •Total bilirubin < 1.5 x upper limit of normal
- •Serum glutamic oxaloacetic transaminase (SGOT) and serum glutamic pyruvate transaminase (SGPT) < 2.5 x upper limit of normal for patients without liver metastases OR SGOT and SGPT < 5 x upper limit of normal for patients with liver metastases
- •Measurable or non-measurable disease will be allowed
- •Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation, up until 30 days after final study treatment; should a woman become pregnant or suspect that she is pregnant while participating in this study, she should inform her treating physician immediately
- •Patients taking substrates, inhibitors, or inducers of cytochrome P450 (CYP)3A4 should be encouraged to switch to alternative drugs whenever possible, given the potential for drug-drug interactions with sirolimus
- •Signed informed consent
排除标准
- •Prior treatment with a mammalian target of rapamycin (mTOR) inhibitor (including sirolimus) is allowed; however, patients with >= grade 3 toxicities with an mTOR inhibitor are excluded
- •Fasting glucose > 126 mg/dL or fasting triglycerides > 150 mg/dL; patients are allowed to be on oral anti-hyperglycemic and anti-lipid therapies, but cannot be on insulin
- •Patients who have had chemotherapy or immunotherapy within 3 weeks of starting study drug, or radiotherapy within 14 days of starting study drug, or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier
- •Patients may not be receiving any other investigational agents or any concomitant antineoplastic therapy, with the exception of androgen ablating agents (for patients with prior prostate cancer)
- •Serious underlying medical or psychiatric illnesses that would, in the opinion of the treating physician, substantially increase the risk for complications related to treatment; similarly, any unstable medical condition that in the opinion of the treating physician or study investigators, would interfere with determination of the study objectives
- •Pregnancy or breastfeeding
- •Major surgery within 4 weeks
研究组 & 干预措施
Treatment (sirolimus)
Patients receive sirolimus PO on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
干预措施: pharmacological study (Other)
Treatment (sirolimus)
Patients receive sirolimus PO on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
干预措施: sirolimus (Drug)
Treatment (sirolimus)
Patients receive sirolimus PO on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
干预措施: laboratory biomarker analysis (Other)
结局指标
主要结局
Change in fasting glucose and fasting triglycerides
时间窗: Baseline to 29 days
These data will be analyzed by fitting mixed effects models for longitudinal data. A model linear in time with random patient intercept and slope effects will be fit initially and residuals examined. If a linear model does not fit the data adequately a quadratic term will be added. Simple paired t-tests of the glucose and triglyceride levels on day 8, 15, and 29 relative to baseline will also be performed.
次要结局
- Change in tumor size assessed using RECIST(Up to 2 years)
- Correlation of toxicities graded using CTCAE version 4.0 with glucose/triglyceride changes(Up to 2 years)
- Regulatory T cells (Tregs)(Baseline to 28 days)
- Association between genetic variants and changes in fasting glucose and triglycerides(Up to 12 months)