Neoplasms

All Conditions

Digestive System Diseases

Rare Diseases

Carcinoma

Carcinoma, Hepatocellular

Liver Neoplasms

Bile Duct Diseases

Liver Diseases

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Biliary Tract Diseases

Primary Liver Cancer

Hematinics

All Drugs and Chemicals

Anticoagulants

Micronutrients

Bone Density Conservation Agents

Liver Extracts

Edetic Acid

Pentetic Acid

Antidotes

Protective Agents

Chelating Agents

Iron

Iron Chelating Agents

Calcium

Calcium, Dietary

Patient receives each of these over one minute. For the gadoxetate disodium, dynamic imaging is performed immediately and imaging is performed at 20 minutes. For the gadobutrol, dynamic imaging is performed immediately.

Contrast-enhanced Magnetic Resonance Imaging

Gadobutrol

Gadoxetate Disodium

Janio Szklaruk, MD, PHD

This clinical trial studies contrast-enhanced magnetic resonance imaging (MRI) in detecting nonmalignant and malignant liver lesions. Diagnostic procedures, such as MRI, may help find and diagnose nonmalignant and malignant liver lesions. Contrast agents, such as gadoxetate disodium and gadobutrol, may help doctors to see MRI images more clearly.

PRIMARY OBJECTIVES:

I. To compare the specificity of contrast enhanced MRI using a liver specific agent Eovist (gadoxetate disodium) versus the combined use of Eovist and an intravascular-extracellular agent Gadavist (gadobutrol) for the radiologic detection and characterization of liver lesions via clinical stability and follow up imaging.

OUTLINE:

Patients receive gadoxetate disodium intravenously (IV) over 1 minute and undergo MRI. Patients then receive gadobutrol IV over 1 minute at the 20 minute mark during MRI.

Contrast-enhanced MRI in Detecting Benign and Malignant Liver Lesions

Radiologic Detection and Characterization of Benign and Malignant Liver Lesions in Contrast-Enhanced MRI

Summary statistics of sensitivity, specificity, true positives, true negatives, false positives, and false negatives will be provided for gadoxetate disodium and gadoxetate disodium + gadobutrol method. Accuracy, sensitivity, specificity, positive predictive value, and negative predictive value will be estimated along with corresponding 95% confidence intervals for the two methods. Comparison between the two methods will be made following method by Obuchowski. Other statistical analyses will be carried out as appropriate.

National Cancer Institute (NCI)

M.D. Anderson Cancer Center

Skin and Connective Tissue Diseases

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Breast Neoplasms

Prostatic Neoplasms

Neuroendocrine Tumors

Neuroendocrine Tumor

Gastrointestinal Agents

Pancrelipase

Pancreatin

Gadolinium 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetate

Adult participants, who were scheduled for repeated enhanced magnetic resonance imaging (MRI), receive a linear gadoliniumbased contrast agent (GBCA, i.e. Eovist/ Primovist, MultiHance or Omniscan) prior to MRI. Each participant will receive the same GBCA throughout the study.

Adult participants, who were scheduled for repeated enhanced magnetic resonance imaging (MRI), receive a macrocyclic gadolinium-based contrast agent (GBCA, i.e. Gadavist/ Gadovist, Dotarem, Magnescope or ProHance) prior to MRI. Each participant will receive the same GBCA throughout the study.

Adult participants who were never exposed to any gadolinium-based contrast agent and matching the population characteristics of the two GBCA arms. They will not receive any gadolinium-based contrast agent over the study course, but may undergo clinically indicated imaging (e.g. unenhanced magnetic resonance imaging (MRI), unenhanced or enhanced computed tomography, ultrasound and/or X-ray).

Motor Tests

Cognitive Tests

The UE-MRI of the brain will be performed at baseline and at the year 5 visit in order to exclude presence of a significant MRI abnormality

Unenhanced-MRI of the brain

Blood samples and spontaneous urine specimens will be collected through the course of the study to measure Gd concentration

Gadolinium Measurements

Administered as defined by the treating physician as part of routine clinical practice

Gadoxetate disodium

Gadobenate dimeglumine

Gadodiamide

Gadoterate meglumine

Gadoteridol

Nathalie LE FUR, PhD

Frantz HEBERT

Ronald Korn, MD

Valentine Mildred

Carla Harmath, MD

Teresa Osmulski

Praveen Sudhindra, MD

Mukesh Harisinghani, MD

Fishman Michael, MD

Joseph Yap

Leo Tsai, MD

Ricardo Sanchez, MD

Sara Schiller

Boris Nicolas Bloch, MD

Lauren Burke, MD

Rebecca Jordan

Nabeel SARWANI, MD

Meera Kasireddy

Ryan Lee, MD

Sydney Haldeman Sydney

Takeshi Yokoo, MD

Riya Nellippallil

Khaled Elsayes, MD

Nolan Caroll

Bruce Richard, MD

Patricia Moura

Joilda Batista de Almeida Rego, MD

Keyla Deucher

Cassiano Mateus Forcelini, MD

Brenda Santos

Ivan Pedrollo, MD

Marcela Maria Dutra

Israel Silva Maia, MD

Nicole Rabello

Luis Eduardo Werneck de Carvalho, MD

Luciana Cubas Volpe

Kathia Abdalla

Study Coordinator

Lis Gomes, MD

Gilberto Szarf

Ronaldo Baroni, MD

Samir Chenaf

Sebastien MOLIERE, MD

Alfonso Cerase, MD

Anna Ianza

Alessandra Guglielmi, MD

YoungJi Lee

Dong Joon Kim, MD

Hwasong Lee

Sang Soo Shin, MD

JinSil Choi

Won Chang, MD

Hayun Jung

Hae Woong Jeong, MD

Yun Jung

Jeong Heo, MD

Gyu Won Kim

JuYeon Cho,, MD

so hyun Kim

Joon Jeong, MD

DaJeong Kwon

Chang-hwan Choi, MD

This study is a postmarketing requirement jointly carried out by four NDA holders (Bayer AG, Bracco, GE Healthcare and Guerbet) and the CRO IQVIA.

The study aims to create detailed images of the organs and tissue of the human body during x-ray, CT-scan or MRI investigations, doctors are using contrast media (a kind of dye) which can be given to patients by injection into a blood vessel or by mouth.

In this study researchers want to find out whether so called gadolinium-based contrast agents (GBCAs) have an effect on body movement and mental skills when given to participants multiple times within 5 years.

The study plans to enroll about 2076 participants suffering from a condition for which they are likely to have at least annually a MRI or another imaging examinations. Only adults up to 65 years will be considered to join this study. During the study duration of 5 years participants will receive annually a MRI or other imaging tests (such as CT-scan, x-ray) and will visit the study doctor at least 7 times for physical examinations, laboratory investigations and tests on body movement and mental skills.

The primary objective of the study is to assess the potential effect of repeated exposure to either a linear or a macrocyclic gadolinium-based contrast agent (GBCA) on change from baseline to Year 5 in composite measure of motor and cognitive function among neurologically normal adults in comparison to a matched non-GBCA- exposed control group.

The secondary objectives comprise the assessment of the following endpoints in GBCA-exposed participants as compared to controls a) changes from baseline in composite measure of motor and cognitive function post-baseline on yearly basis (Years 1 to 4); b) changes from baseline in each individual test of motor and cognitive function on yearly basis (Years 1 to 5). Total Gd concentrations in blood and urine samples on yearly basis (Years 1 to 5) and adverse events will be collected as secondary objectives.

Of note : The study is considered interventional because of the addition of UE-MRI scans for all participants, as well as blood sampling and the administration of the motor and cognitive tests. The GBCA administered as part of the contrast-enhanced MR imaging in the experimental arms is not the intervention in this study. Neither the protocol nor the investigators assign patients to a specific GBCA as part of the study, making this part of the study observational rather than interventional. The participants were already scheduled, prior to study screening, to undergo CE-MRI as part of their clinical care. The choice of GBCA for the CE-MRI will be based on medical need and institutional usage of GBCA, independent of study participation.

Effect on Body Movement and Mental Skills in Patients Who Received Gadolinium-based Contrast Media for Magnetic Resonance Examination Multiple Times Within 5 Years

Prospective Evaluation of Potential Effects of Repeated Gadolinium-based Contrast Agent (GBCA) Administrations of the Same GBCA on Motor and Cognitive Functions in Neurologically Normal Adults in Comparison to a Non-GBCA Exposed Control Group

The endpoint is a composite z score, defined as the weighted sum of the z scores of the individual tests

Bayer AG (Sponsor)

Bracco (Sponsor)

GEHC (Sponsor)

Guerbet

Symptoms and General Pathology

Neoplasm Metastasis

Neoplastic Processes

The subjects will be randomized into two groups. Both groups will undergo two complete protocol liver MRs for known or suspected CRC metastasis, one exam with gadoxetate disodium and the other exam with gadobenate dimeglumine, within an interval of 3-10 days, but in opposite order, determined randomly.

Gadoxetate disodium is now mainly used for the purpose of HBP liver MR imaging to save MR scanner time and total examination time.

The most commonly used MR contrast agent in abdominal imaging is gadobenate dimeglumine, which has mainly the characteristics of an extracellular agent used for most indications of MR examinations.

Samuel Chang, MD

Tracey MacDermott

If an abbreviated HBP protocol liver MR with gadobenate dimeglumine is shown clinically comparable to standard of care liver MR with gadoxetate disodium for detecting hepatic metastasis from colorectal cancer, its use will save time, cost, and patients' effort.

The goal is to:

* Estimate and compare the diagnostic performance, including sensitivity, specificity, positive/negative predictive value, and area under the receiver operating characteristics (AUROC), of abbreviated protocol liver magnetic resonance (MR) with hepatobiliary phase (HBP) using gadobenate dimeglumine for detecting liver metastases, with 1) abbreviated protocol liver MR with HBP using gadoxetate disodium, 2) standard of care complete protocol liver MR using gadoxetate disodium, and 3) complete protocol liver MR using gadobenate dimeglumine.
* Estimate and compare quantitative measures of HBP images (liver enhancement ratio, lesion contrast to noise and signal to noise ratios \[CNR and SNR\]) for both gadobenate dimeglumine and gadoxetate disodium.
* Qualitatively assess the preference, or lack thereof, of radiologists regarding the images generated by abbreviated protocol liver MR with HBP using gadobenate dimeglumine versus abbreviated protocol liver MR with HBP using gadoxetate disodium.

This is a prospective study. The subjects will be randomized into two groups. Both groups will undergo two complete protocol liver MRs for known or suspected CRC metastasis, one exam with gadoxetate disodium and the other exam with gadobenate dimeglumine, within an interval of 3-10 days, but in opposite order, determined randomly. From the complete protocol liver MR with both contrast agents, an image set of abbreviated HBP protocol liver MR for each agent will be obtained (Fig.1).Two week-intervals will be placed between the evaluations of different image sets of a patient, and the images will be presented in a different random order to each evaluating radiologist. The schedule of random order of protocol liver MRs and presentation of images to radiologists will be determined by the project biostatistician.

We have attempted to mitigate any potential conflict of interest through randomization of the order of exams and blinding the image evaluators to contrast agents.

Comparison of Contrast Agents in Liver MR for the Detection of Hepatic Metastases

Evaluation of Liver MR With an Abbreviated Gadobenate Dimeglumine Hepatobiliary Phase Protocol in Comparison to Liver MR With Gadoxetate Disodium for the Detection of Hepatic Metastases

The primary performance diagnostic will be sensitivity, similar to the recently published retrospective study by Canellas et al. (2019). In addition to other diagnostic performance metrics of interest (e.g., specificity, AUROC), lesions will be analyzed descriptively in terms of number of metastases detected and lesion size.

Mixed effects regression models will again be used to compare the three outcomes between methods, accounting for correlated data. The specific link function of the regression models will depend on the distributional characteristics of each outcome (e.g., logit link for dichotomous outcomes; linear regression for continuously measured outcomes).

The quality of amHBP and aeHBP images will be assessed with ordinal response mixed effect models that include right/left image as a covariate. We will assess if there was any reader specific and/or general bias to prefer an image on the left or the right of a screen, regardless of the amHBP or aeHBP, and consider this when modeling the probability of preference of amHBP over aeHBP. We will estimate the relative probabilities of no-preference, amHBP preference, or aeHBP preference.

The primary analysis will use pathology as the gold standard, if available, but will revert to long term imaging in the absence of pathology. To address the potential impact of this limitation, we will also conduct an exploratory analysis to compare the sensitivity and specificity of the imaging methods by each gold standard.

We will also conduct an exploratory analysis to test the validity of long term imaging as a gold standard against available pathology reports.

In addition to analyses for the primary aims, additional analyses will be conducted to examine patient time associated with each imaging method; time metrics can be compared between imaging methods in absolute terms, but also proportionally to sensitivity.

In addition to analyses for the primary aims, additional analyses will be conducted to examine cost associated with each imaging method; cost metrics can be compared between imaging methods in absolute terms, but also proportionally to sensitivity.

Bracco Diagnostics, Inc

University of Colorado, Denver

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Adenocarcinoma

Patients receive gadoxetate disodium IV and then undergo enhanced liver MRI.

Magnetic Resonance Imaging

Gilbert Whang

This pilot clinical trial studies magnetic resonance imaging (MRI) with gadoxetate disodium in measuring tumors in patients with liver cancer. Diagnostic procedures, such as MRI with gadoxetate disodium, may help find and diagnose liver cancer and find out how far the disease has spread. It is not yet known whether MRI with gadoxetate disodium provides a more precise measurement of liver tumors than standard computed tomography (CT).

PRIMARY OBJECTIVES:

I. To evaluate the precision of gadoxetate (gadoxetate disodium)-enhanced MRI in evaluating lesion size.

II. To evaluate if there is a subjective improvement in the delineation of hepatocellular carcinoma (HCC) in the hepatocellular phase of contrast administration.

III. To further assess the sensitivity of gadoxetate-enhanced MRI for the detection of HCC.

SECONDARY OBJECTIVES:

I. To evaluate the reproducibility of various tumor measurement techniques in the evaluation of HCC.

II. To further evaluate how administration of gadoxetate affects diffusion weighted imaging.

OUTLINE:

Patients receive gadoxetate disodium intravenously (IV) and then undergo enhanced liver MRI.

After completion of study, patients are followed up at 2, 4, 8, and 12 months.

MRI With Gadoxetate Disodium in Measuring Tumors in Patients With Liver Cancer

MR Techniques in the Evaluation of Hepatocellular Carcinoma: Gadoxetate

Initially, a random effects analysis of variance (ANOVA) will be performed for each type of image (CT vs. MRI), for each phase (4 for CT and 5 for MRI) and for each method of measuring "size" (1-, 2-, and 3-dimensional) - for a total of 27 ANOVAs. Lesion, radiologist, and replication (for the 20 target lesions measured twice) will all be random effects; the inter-reader and the intra-reader variability will be estimated from these models and 95% confidence intervals will be constructed.

ADC values will be recorded for uninvolved liver parenchyma and for tumors before and after administration of gadoxetate disodium.

University of Southern California

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Contrast-enhanced MRI in Detecting Benign and Malignant Liver Lesions	NCT02156739	Hepatocellular ... Liver and Intra... Metastatic Mali... Primary Maligna...	Contrast-enhanc... Gadobutrol Gadoxetate Diso...	18 Years -	M.D. Anderson Cancer Center
Effect on Body Movement and Mental Skills in Patients Who Received Gadolinium-based Contrast Media for Magnetic Resonance Examination Multiple Times Within 5 Years	NCT04373564	Motor Function Cognitive Funct... Contrast Media	Motor Tests Cognitive Tests Unenhanced-MRI ... Gadolinium Meas... Gadoxetate diso... Gadobenate dime... Gadodiamide Gadoterate megl... Gadobutrol Gadoteridol	18 Years - 64 Years	Guerbet
Comparison of Contrast Agents in Liver MR for the Detection of Hepatic Metastases	NCT04973007	Oligometastatic... Liver Metastase... Colorectal Canc...	Gadoxetate diso... Gadobenate dime...	18 Years -	University of Colorado, Denver
Contrast-enhanced MRI in Detecting Benign and Malignant Liver Lesions	NCT02156739	Hepatocellular ... Liver and Intra... Metastatic Mali... Primary Maligna...	Contrast-enhanc... Gadobutrol Gadoxetate Diso...	18 Years -	M.D. Anderson Cancer Center
Contrast-enhanced MRI in Detecting Benign and Malignant Liver Lesions	NCT02156739	Hepatocellular ... Liver and Intra... Metastatic Mali... Primary Maligna...	Contrast-enhanc... Gadobutrol Gadoxetate Diso...	18 Years -	M.D. Anderson Cancer Center
MRI With Gadoxetate Disodium in Measuring Tumors in Patients With Liver Cancer	NCT02578602	Adult Hepatocel... Advanced Adult ... BCLC Stage 0 Ad... BCLC Stage A Ad... BCLC Stage B Ad... BCLC Stage C Ad... BCLC Stage D Ad... Localized Non-R... Localized Resec...	Gadoxetate Diso... Magnetic Resona...	18 Years -	University of Southern California

Spots Global Cancer Trial Database for gadoxetate disodium