Assessment of Carboplatin Clearance Predictors: A PK Study on NCI-Sponsored Clinical Trials or Standard of Care Treatments Using Carboplatin
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 发起方
- NRG Oncology
- 入组人数
- 350
- 试验地点
- 355
- 主要终点
- Accuracy of achieving the targeted carboplatin area under the curve (AUC)
研究概览
简要总结
This trial studies how well iohexol works in helping doctors calculate the dose of carboplatin given to patients with cancer. Drugs used in chemotherapy, such as carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Understanding how to best calculate the dose of carboplatin given to patients with cancer may help doctors learn how to improve the use of carboplatin in the future.
详细描述
PRIMARY OBJECTIVES:
I. Evaluate the success of targeting a carboplatin area under the curve (AUC) with our current approach to dosing carboplatin.
II. Assess the performance of Cockcroft-Gault (CG), four-variable Modification of Diet in Renal Disease (MDRD-4), and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) based on isotope dilution mass spectrometry (IDMS) calibrated serum creatinine in predicting measured glomerular filtration rate (mGFR) in patients with cancer.
III. Define the relationship of mGFR and carboplatin clearance in patients with cancer.
SECONDARY OBJECTIVES:
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
- Male
- 接受健康志愿者
- 否
入选标准
- •Patients must have the psychological ability and general health that permits completion of the study requirements and required follow up
- •For men who are sexually active, the need for use of medically acceptable contraception will be dictated by the primary treatment plan/protocol
- •Study accrual was closed to women on 08/18/2021 and accrual is now only open to males in order to meet accrual goals and study objectives. (11-AUG-2021)
- •Any patients who will receive treatment with intravenous carboplatin (any AUC, any cycle) on a National Cancer Institute (NCI)-sponsored National Clinical Trial Network (NCTN)-, Experimental Therapeutics Clinical Trials Network (ETCTN)-, trial, local trial, or through standard of care
- •Age >= 18
- •The patient or a legally authorized representative must provide study-specific informed consent prior to study entry
排除标准
- •Treated at an institute where creatinine is not measured with an IDMS calibrated assay
- •History of allergic reactions to computed tomography (CT) contrast, iodine or shellfish, or history of anaphylactic reaction to any food item
- •Recent (last 6 months) episode of acute kidney injury, have sickle cell disease, or have current indwelling nephrostomy tubes
- •Edema beyond trace edema, because this will impact iohexol equilibration and distribution
- •Ascites (including pleural effusion) beyond trace ascites, because this will impact iohexol equilibration and distribution
- •Whole- or part-limb amputees, because this will impact iohexol equilibration and distribution
- •Inability to maintain a constant dose and schedule of anti-inflammatory agents, diuretics, angiotensin II receptor blockers (ARB) and angiotensin converting enzyme inhibitors (ACEi) for one week prior to study visit, as this impacts renal function. If the patient is on a nonsteroidal anti-inflammatory drug (NSAID), diuretic, ARB or ACEi, they are eligible as long as these agents are taken on a set schedule for 7 or more days prior to study (and not on an "as needed" basis as that can cause fluctuations in renal function)
- •Inadequate venous access to obtain pharmacokinetic (PK) specimens
- •Multinodular goiter, Graves' disease or autoimmune thyroiditis, per iohexol package insert (hypothyroidism is allowed)
研究组 & 干预措施
Treatment (iohexol, standard care carboplatin, blood samples)
Patients receive iohexol IV over 30-60 seconds. Patients then receive standard of care carboplatin IV. Patients also undergo collection of 7-8 blood samples for analysis.
干预措施: Biospecimen Collection (Procedure)
Treatment (iohexol, standard care carboplatin, blood samples)
Patients receive iohexol IV over 30-60 seconds. Patients then receive standard of care carboplatin IV. Patients also undergo collection of 7-8 blood samples for analysis.
干预措施: Iohexol (Drug)
Treatment (iohexol, standard care carboplatin, blood samples)
Patients receive iohexol IV over 30-60 seconds. Patients then receive standard of care carboplatin IV. Patients also undergo collection of 7-8 blood samples for analysis.
干预措施: Carboplatin (Drug)
结局指标
主要结局
Accuracy of achieving the targeted carboplatin area under the curve (AUC)
时间窗: Up to 4 weeks
Will be quantified by the median percentage error (PE), root-mean-squared error (RMSE), interquartile range (IQR) of the residuals, and median absolute percentage error (APE). In addition, the percentage of patients for which the observed carboplatin AUC is within 17% of target will be calculated. The actual AUC will be quantified using atomic absorption spectrophotometry.
Precision of the formula for eGFR currently in existence in patients with cancer
时间窗: Up to 4 weeks
Will be quantified by the median PE, RMSE, IQR of the residuals, and median APE will be used to assess the accuracy of each model's eGFR values for predicting mGFR. In addition, will calculate the percentage of patients for which eGFR is within 30%, 20%, and 10% of mGFR.
Bias of the formula for estimated glomerular filtration rate (eGFR) currently in existence in patients with cancer
时间窗: Up to 4 weeks
Will be quantified by the median PE, RMSE, IQR of the residuals, and median APE will be used to assess the accuracy of each model's eGFR values for predicting measured (m)GFR. In addition, will calculate the percentage of patients for which eGFR is within 30%, 20%, and 10% of mGFR.
Correlation between carboplatin clearance (CL) and mGFR
时间窗: Up to 4 weeks
Assessed by regression analysis. Carboplatin clearance will be derived by Empirical Bayes estimation using the POSTHOC option implemented in NONMEM. Will perform regression on the relationship between CL and mGFR. Initially this will follow a linear relationship analogous to the Calvert formula (CL = A + B\* mGFR), and will test if the observed values for A and B are significantly different from those defined by Calvert as A = 25 mL/min and B = 1 (unitless). Will also perform regression by other means, e.g. after log transformation of the data, and assess if this results in a formula that performs better than the Calvert formula or the initial linear model. In addition, the impact of covariates on this relationship will be explored.
Precision of achieving the targeted carboplatin AUC
时间窗: Up to 4 weeks
Will be quantified by the median PE, RMSE, IQR of the residuals, and median APE. In addition, the percentage of patients for which the observed carboplatin AUC is within 17% of target will be calculated. The actual AUC will be quantified using atomic absorption spectrophotometry.
次要结局
- Divergence of eGFR from mGFR(Up to 4 weeks)
- Success rate of achieving the target carboplatin AUC in patients in whom the carboplatin dose is capped(Up to 4 weeks)
- Ability of markers in addition to creatinine in pre-treatment serum to better estimate kidney function in patients with cancer(Up to 4 weeks)
- Relationship between carboplatin exposure and toxicity(Up to 4 weeks)