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Evaluation of Dosing Procedures of Chemotherapy Treatment (Carboplatin) With the Contrast Agent Iohexol

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ClinicalTrials.gov Identifier: NCT03997370
Recruitment Status : Recruiting
First Posted : June 25, 2019
Last Update Posted : June 2, 2022
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
NRG Oncology

Study Description
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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.

Condition or disease Intervention/treatment Phase
Malignant Solid Neoplasm Procedure: Biospecimen Collection Drug: Carboplatin Drug: Iohexol Phase 1

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.

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 250 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Assessment of Carboplatin Clearance Predictors: A PK Study on NCI-Sponsored Clinical Trials or Standard of Care Treatments Using Carboplatin
Actual Study Start Date : November 18, 2019
Estimated Primary Completion Date : September 15, 2022
Estimated Study Completion Date : September 15, 2023

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: 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.
 Procedure: Biospecimen Collection
Undergo collection of blood samples
Other Names:
  • Biological Sample Collection
  • Biospecimen Collected

Drug: Carboplatin
Given IV
Other Names:
  • Blastocarb
  • Carboplat
  • Carboplatin Hexal
  • Carboplatino
  • Carboplatinum
  • Carbosin
  • Carbosol
  • Carbotec
  • CBDCA
  • Displata
  • Ercar
  • JM-8
  • Nealorin
  • Novoplatinum
  • Paraplatin
  • Paraplatin AQ
  • Paraplatine
  • Platinwas
  • Ribocarbo

Drug: Iohexol
Given IV
Other Name: Omnipaque


Outcome Measures
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Primary Outcome Measures :
  1. Accuracy of achieving the targeted carboplatin area under the curve (AUC) [ Time Frame: 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.

  2. Precision of achieving the targeted carboplatin AUC [ Time Frame: 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.

  3. Bias of the formula for estimated glomerular filtration rate (eGFR) currently in existence in patients with cancer [ Time Frame: 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.

  4. Precision of the formula for eGFR currently in existence in patients with cancer [ Time Frame: 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.

  5. Correlation between carboplatin clearance (CL) and mGFR [ Time Frame: 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.


Secondary Outcome Measures :
  1. Divergence of eGFR from mGFR [ Time Frame: Up to 4 weeks ]
    The bias of eGFR versus mGFR will be modeled as a function of the patient's characteristics.

  2. Success rate of achieving the target carboplatin AUC in patients in whom the carboplatin dose is capped [ Time Frame: Up to 4 weeks ]
    Among patients with eGFR > 125 mL/min, precision and bias will be estimated relative to the target carboplatin AUC.

  3. Relationship between carboplatin exposure and toxicity [ Time Frame: Up to 4 weeks ]
    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.

  4. Ability of markers in addition to creatinine in pre-treatment serum to better estimate kidney function in patients with cancer [ Time Frame: Up to 4 weeks ]
    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.


Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
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
  • 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)
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03997370


Locations
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Sponsors and Collaborators
NRG Oncology
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Sarah E Taylor NRG Oncology
More Information
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Responsible Party: NRG Oncology
ClinicalTrials.gov Identifier: NCT03997370    
Other Study ID Numbers: NRG-GY022
NCI-2019-04008 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
NRG-GY022 ( Other Identifier: NRG Oncology )
NRG-GY022 ( Other Identifier: CTEP )
U10CA180868 ( U.S. NIH Grant/Contract )
First Posted: June 25, 2019    Key Record Dates
Last Update Posted: June 2, 2022
Last Verified: June 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.
URL: https://grants.nih.gov/policy/sharing.htm

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Carboplatin
Antineoplastic Agents