Dotarem vs Gadobutrol Contrast for Breast MRI

Contrast Enhanced Breast MRI: Comparison of Two Macrocyclic Gadolinium-Based Contrast Agents: Gadoterate Meglumine (Dotarem) and Gadobutrol (Gadavist). A Prospective Study.

In this randomized clinical trial, the investigators expect to demonstrate that the MRI contrast agent Dotarem is not less effective in contrast enhancement of breast lesions then Gadavist. Participants will be randomized to receive either Dotarem or Gadavist. In all cases, inclusion criteria will require patients having undergone or scheduled or most likely to be scheduled to undergo tissue sampling with histology results available. The patients will be prospectively and consecutively identified such that the majority of patients included will have been diagnosed with breast cancer, while including benign disease in the minority of patients in each arm. Following randomized enrollment, quantitative, semi-quantitative and qualitative image analysis will be performed to objectively assess for differences in image quality and diagnostic value.

Study Overview

• Status: Recruiting
• Conditions: Breast Diseases
• Intervention / Treatment: Drug: Gadoterate meglumine; Drug: Gadobutrol

Detailed Description

A stratified randomization of participants based on the time of menstural cycle and breast density. Women will then receive their clinically indicated Breast MRI with contrast, using SOC procedures for weight-based dosage. After enrollment, MRI images and medical metadata will be abstracted using the hospital medical records in EPIC and PACS databases. Data to be collected from the medical record includes histology parameters: tumor, tumor type and size, grade, stage and personal data: MRN, accession number, date of birth, date of MRI, age, sex, race/ethnicity, family history. Images will be stripped of identifiers and then coded by a study ID using the third party SanteSoft Dicom Editor software. Medidata will also be coded and stored separately from a mastercode file linking the study ID with the following identifiable information: MRN, accession number, date of birth, and date of MRI.

After a period of data collection, two radiologists blinded to the contrast agent will independently review the the MRIs. This qualitative review will consist of each exam being graded on a scale of 1-(Fail) to 5-(Excellent) contrast enhancement quality. Additionally, each blinded radiologist or designee will conduct the secondary quantitative measurements of the wash-in/wash-out contrast characteristics through use of computer aid design (CAD) in PACS.

• Study Type: Interventional
• Enrollment (Estimated): 258
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Nicolas Bloch, MD; Phone Number: 508-856-2144; Email: b.nicolas.bloch@umassmemorial.org
• Study Contact Backup: Name: Sandra Haskins; Phone Number: 508-736-6251; Email: Sandra.Haskins@umassmed.edu

Study Locations

• United States
  • Massachusetts
    • Worcester, Massachusetts, United States, 01655
      • Recruiting
      • UMass Medical School
      • Contact: Nicolas Bloch, MD; Phone Number: 508-856-2144; Email: b.nicolas.bloch@umassmemorial.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Females age 18 and older
• Scheduled to undergo a clinically indicated MRI of the breast with contrast.
• Have undergone, are scheduled to undergo, or are likely to be scheduled to undergo a breast tissue sampling exam with histology results available within 6 months of their MRI.

Exclusion Criteria:

• Pregnant
• Have already begun therapeutic treatment for breast cancer including surgery (lumpectomy or mastectomy), radiotherapy, or chemotherapy.
• Pre Menopause women outside of the 7-14 days from cycle

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Gadoterate meglumine contrast; 0.2 mL/kg (0.1 mmol/kg) administered as a single IV bolus injection at a rate of 2 mL/second. The FDA-approved product labeling provides weight-adjusted dose volumes as follows: 30 kg: 6 mL; 40 kg: 8 mL; 50 kg: 10 mL; 60 kg: 12 mL; 70 kg: 14 mL; 80 kg: 16 mL; 90 kg: 18 mL; 100 kg: 20 mL; 110 kg: 22 mL; 120 kg: 24 mL; 130 kg: 26 mL; 140 kg: 28 mL; 150 kg: 30 mL.	Drug: Gadoterate meglumine; Participants randomized into this arm will receive gadoterate meglumine contrast for their scheduled breast MRI.; Other Names: Dotarem
Experimental: Gadobutrol contrast; 0.1 mL/kg (0.1 mmol/kg) administered as a single IV bolus injection by power injector. Imaging may begin after administration and then repeat sequentially to determine peak intensity and wash-out. The manufacturer provides weight-based dose volumes as follow: 35 kg: 3.5 mL; 40 kg: 4 mL; 45 kg: 4.5 mL; 50 kg: 5 mL; 60 kg: 6 mL; 70 kg: 7 mL; 80 kg: 8 mL; 90 kg: 9 mL; 100 kg: 10 mL; 110 kg: 11 mL; 120 kg: 12 mL; 130 kg: 13 mL; 140 kg: 14 mL.	Drug: Gadobutrol; Participants randomized into this arm will receive gadobutrol contrast for their scheduled breast MRI.; Other Names: Gadavist

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Quality of breast MRI	Each MRI exam will be graded by two radiologists blinded to the contrast agent using a scale of 1-(Fail- No enhancement or inadequate enhancement of the tumor) to 5-(Excellent- Strong and divisive contrast enhancement of entire tumor when compared to background. Clear and obvious tumor borders.) for the contrast enhancement quality.	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Wash-in/wash-out MRI contrast curve in breast tissues	The wash-in/wash-out MRI contrast curve will be assessed by software that analyzes the MRI images pixel by pixel for signal intensity changes over time on the breast MRI for each participant.	12 months
Maximum relative enhancement (E(max) for contrast breast MRI	The maximum relative enhancement (E(max)) will be assessed by software that analyzes the MRI images pixel by pixel for signal intensity changes over time on the breast MRI for each participant.	12 months
Time to peak enhancement (T(max)) for contrast breast MRI	The mean +/-sd of the time to peak enhancement (T(max)) will be assessed by software that analyzes the MRI images pixel by pixel for signal intensity changes over time on the breast MRI for each participant.	12 months
Maximum enhancement slope for contrast breast MRI	The maximum enhancement slope will be assessed by software that analyzes the MRI images pixel by pixel for signal intensity changes over time on the breast MRI for each participant.	12 months

Collaborators and Investigators

• Sponsor: University of Massachusetts, Worcester
• Collaborators: Guerbet
• Investigators: Principal Investigator: Nicholas Bloch, MD, UMass Medical School

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2021
• Primary Completion (Estimated): March 1, 2025
• Study Completion (Estimated): March 1, 2026

Study Registration Dates

• First Submitted: November 1, 2018
• First Submitted That Met QC Criteria: November 1, 2018
• First Posted (Actual): November 5, 2018

Study Record Updates

• Last Update Posted (Actual): April 23, 2024
• Last Update Submitted That Met QC Criteria: April 19, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Mammography; Breast MRI; Dotarem contrast; Gadobutrol contrast; wash-in/wash-out contrast curve; Contrast enhanced MRI
• Additional Relevant MeSH Terms: Skin Diseases; Breast Diseases; Molecular Mechanisms of Pharmacological Action; Chelating Agents; Sequestering Agents; Gadolinium 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetate
• Other Study ID Numbers: H00020209

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No