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

NRG Oncology

Status and phase: Enrolling; Phase 1

Conditions: Malignant Solid Neoplasm

Treatments: Procedure: Biospecimen Collection; Drug: Carboplatin; Drug: Iohexol

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT03997370

U10CA180868 (U.S. NIH Grant/Contract)

NCI-2019-04008 (Registry Identifier)

NRG-GY022

Details and patient eligibility

About

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.

Full 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.

Enrollment: 350 estimated patients

Sex: Male

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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)

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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350 participants in 1 patient group

Treatment (iohexol, standard care carboplatin, blood samples)

Experimental group

Description:

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.

Treatment:

Drug: Iohexol

Drug: Carboplatin

Procedure: Biospecimen Collection