Brief Summary
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.
Brief Title
Evaluation of Dosing Procedures of Chemotherapy Treatment (Carboplatin) With the Contrast Agent Iohexol
Detailed Description
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:
I. Evaluate the divergence of estimated (e)GFR from mGFR based on patient demographic and other characteristics, thus identifying those most likely to benefit from determination of mGFR over use of eGFR.
II. Determine the success rate of achieving the target carboplatin AUC in patients in whom the carboplatin dose is capped.
III. Evaluate the relationship between carboplatin exposure and toxicity. IV. Assess the ability of markers other than creatinine in pre-treatment serum to better estimate kidney function in patients with cancer.
OUTLINE:
Patients receive iohexol intravenously (IV) over 30-60 seconds. Patients then receive standard of care carboplatin IV. Patients also undergo collection of 7-8 blood samples for analysis.
After completion of study, patients are followed up for 3-4 weeks.
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:
I. Evaluate the divergence of estimated (e)GFR from mGFR based on patient demographic and other characteristics, thus identifying those most likely to benefit from determination of mGFR over use of eGFR.
II. Determine the success rate of achieving the target carboplatin AUC in patients in whom the carboplatin dose is capped.
III. Evaluate the relationship between carboplatin exposure and toxicity. IV. Assess the ability of markers other than creatinine in pre-treatment serum to better estimate kidney function in patients with cancer.
OUTLINE:
Patients receive iohexol intravenously (IV) over 30-60 seconds. Patients then receive standard of care carboplatin IV. Patients also undergo collection of 7-8 blood samples for analysis.
After completion of study, patients are followed up for 3-4 weeks.
Completion Date
Completion Date Type
Estimated
Conditions
Malignant Solid Neoplasm
Eligibility Criteria
Inclusion Criteria:
* 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)
* Male sex
* 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
Exclusion Criteria:
* 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)
* 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)
* Male sex
* 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
Exclusion Criteria:
* 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)
Inclusion Criteria
Inclusion Criteria:
* 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)
* Male sex
* 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
* 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)
* Male sex
* 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
Gender
Male
Gender Based
false
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Minimum Age
18 Years
NCT Id
NCT03997370
Org Class
Other
Org Full Name
NRG Oncology
Org Study Id
NRG-GY022
Overall Status
Recruiting
Phases
Phase 1
Primary Completion Date
Primary Completion Date Type
Estimated
Official Title
Assessment of Carboplatin Clearance Predictors: A PK Study on NCI-Sponsored Clinical Trials or Standard of Care Treatments Using Carboplatin
Primary Outcomes
Outcome Description
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.
Outcome Measure
Accuracy of achieving the targeted carboplatin area under the curve (AUC)
Outcome Time Frame
Up to 4 weeks
Outcome Description
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.
Outcome Measure
Precision of achieving the targeted carboplatin AUC
Outcome Time Frame
Up to 4 weeks
Outcome Description
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.
Outcome Measure
Bias of the formula for estimated glomerular filtration rate (eGFR) currently in existence in patients with cancer
Outcome Time Frame
Up to 4 weeks
Outcome Description
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.
Outcome Measure
Precision of the formula for eGFR currently in existence in patients with cancer
Outcome Time Frame
Up to 4 weeks
Outcome Description
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.
Outcome Measure
Correlation between carboplatin clearance (CL) and mGFR
Outcome Time Frame
Up to 4 weeks
Secondary Ids
Secondary Id
NCI-2019-04008
Secondary Id
NRG-GY022
Secondary Id
NRG-GY022
Secondary Id
U10CA180868
Secondary Outcomes
Outcome Description
The bias of eGFR versus mGFR will be modeled as a function of the patient's characteristics.
Outcome Time Frame
Up to 4 weeks
Outcome Measure
Divergence of eGFR from mGFR
Outcome Description
Among patients with eGFR \> 125 mL/min, precision and bias will be estimated relative to the target carboplatin AUC.
Outcome Time Frame
Up to 4 weeks
Outcome Measure
Success rate of achieving the target carboplatin AUC in patients in whom the carboplatin dose is capped
Outcome Description
Will be described by the regression parameters for the estimated relationship between carboplatin AUC and platelet count, neutrophil count, and non-hematologic grade 3 toxicities.
Outcome Time Frame
Up to 4 weeks
Outcome Measure
Relationship between carboplatin exposure and toxicity
Outcome Description
These markers will include (but are not limited to) cystatin C, beta-2-microglobulin (B2M), and beta-trace-protein (BTP). Will use these markers and patient covariates (e.g. sex, race, weight etc.) as predictors for mGFR in regression efforts.
Outcome Time Frame
Up to 4 weeks
Outcome Measure
Ability of markers in addition to creatinine in pre-treatment serum to better estimate kidney function in patients with cancer
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Actual
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Ken Lin
Investigator Email
kelin@montefiore.org
MeSH Terms
SPECIMEN HANDLING
CARBOPLATIN
IOHEXOL
CLINICAL LABORATORY TECHNIQUES
DIAGNOSTIC TECHNIQUES AND PROCEDURES
DIAGNOSIS
INVESTIGATIVE TECHNIQUES
COORDINATION COMPLEXES
ORGANIC CHEMICALS
TRIIODOBENZOIC ACIDS
IODOBENZOATES
BENZOATES
ACIDS, CARBOCYCLIC
CARBOXYLIC ACIDS
BENZENE DERIVATIVES
HYDROCARBONS, AROMATIC
HYDROCARBONS, CYCLIC
HYDROCARBONS