Pharmacokinetic Profiling of Pembrolizumab (Keytruda&Amp;Reg;) and Nivolumab (Opdiva&Amp;Reg;) in Patients With Melanoma and/or Non-Small Cell Lung Cancer: Clinical Validation of a Mass Spectrometry-based Assay
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- Mayo Clinic
- 入组人数
- 13
- 试验地点
- 1
- 主要终点
- Measurement of patient samples for pembrolizumab
研究概览
简要总结
This early phase I study collects blood samples and monitors the levels of pembrolizumab and nivolumab as they move through the body in patients with melanoma and/or non-small cell lung cancer. Pembrolizumab and nivolumab are a monoclonal antibodies that may interfere with the ability of cancer cells to grow and spread. Studying samples of blood in the laboratory from patients receiving pembrolizumab and nivolumab may help doctors learn more about the effects of pembrolizumab and nivolumab on cells. It may also help doctors understand how well patients respond to treatment. Information from this study may be used in the future to guide physicians to make dosage adjustments based on serum concentrations of drug to minimize adverse side effects and maximize the effect of the drug.
详细描述
PRIMARY OBJECTIVE:
I. To perform a steady-state PK study on patients who are taking monoclonal antibody therapy (25 patients starting pembrolizumab and 25 patients starting nivolumab for melanoma or non-small cell lung cancer).
II. Develop and validate a liquid chromatography tandem mass spectrometry (LC-MS/MS) assay to measure pembrolizumab and nivolumab in serum.
III. Measure patient samples for pembrolizumab/nivolumab at various clinical time points.
IV. Use the pharmacokinetic data (drug concentrations) to determine the area under the curve (AUC), maximum observed serum concentration (Cmax), clearance, half-life (t1/2), and trough steady-state drug concentrations.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
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
- •Adults who are at steady-state and taking monoclonal antibody therapy with pembrolizumab or nivolumab for melanoma or non-small cell lung cancer. Steady-state for pembrolizumab is week 21 or later and for nivolumab is week 14 or later from the initial infusion
排除标准
- •Patients not taking pembrolizumab or nivolumab or taking pembrolizumab or nivolumab for other indications (not melanoma or non-small cell lung cancer).
结局指标
主要结局
Measurement of patient samples for pembrolizumab
时间窗: Through study completion at several time points, an average of 3 weeks after taking pembrolizumab for at least 21 weeks.
Using a validated LDT liquid chromatography tandem mass spectrometry assay measure the concentration of pembrolizumab in serum.
Measurement of patient samples for nivolumab
时间窗: Through study completion at several time points, an average of 1 month after taking nivolumab for at least 14 weeks
Using a validated LDT liquid chromatography tandem mass spectrometry assay measure the concentration of nivolumab in serum.
Correlation of steady-state concentrations of nivolumab correlate with clinical efficacy
时间窗: Through study completion, an average of 1 month after taking nivolumab for at least 14 weeks
Will assess if therapeutic drug monitoring correlates with efficacy and/or toxicity of nivolumab. Concentrations in serum will be determined using a LDT mass spectrometry assay.
Clinical efficacy
时间窗: After 6 months (24 weeks or more) of treatment
Tumor response will be determined using Response Evaluation Criteria in Solid Tumors1.1 criteria. Clinical efficacy defined as achieving an objective response (complete response or partial response) versus stable disease, or disease progression.
Development and validation of a laboratory developed test (LDT) using liquid chromatography tandem mass spectrometry to measure pemborlizumab and nivolumab.
时间窗: Up to 1 year
Verify the accuracy, precision, linearity, sensitivity and specificity of a mass spectrometry assay for pembrolizumab and nivolumab in serum
Correlation of steady-state concentrations of pembrolizumab correlate with clinical efficacy and/or toxicity
时间窗: Through study completion, an average of 3 weeks after taking pembrolizumab for at least 21 weeks.
Will assess if therapeutic drug monitoring correlates with efficacy and/or toxicity of pembrolizumab. Concentrations in serum will be determined using a LDT mass spectrometry assay.
Presence of auto-immune side effects
时间窗: Through study completion, an average of 1 month
Adverse events will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse events, version 4.0. Investigators will indicate if it was potentially immune related (i.e. grade 3-4 adverse events such as pneumonitis, diarrhea/colitis, hypophysitis/adrenal insufficiency, hyper/hypothyroidism, autoimmune hepatitis, severe skin reactions, nephritis/kidney failure, uveitis, myositis) in combination with other basic laboratory tests that are routinely monitored. Will use multiple variable regression modeling in Statistical Analysis System version 9.4 or other statistical software.
次要结局
未报告次要终点
研究者
Paul Jannetto
Principal Investigator
Mayo Clinic