Clinical trial NCT01067976: Efficacy and Safety of Gadobutrol 1.0 Molar (Gadovist) for Breast MRI
Official title: An Open Label, Multi-center, Phase 3 Study With Corresponding Blinded Image Reading to Determine the Efficacy and Safety of a Single Intravenous Injection of 0.1 mmol/kg Body Weight of Gadobutrol 1.0 Molar (Gadovist®) in Patients With Newly Diagnosed Breast Cancer Referred for Contrast-enhanced Breast MRI
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Breast Cancer
Diagnostic Imaging
Keywords: Breast Cancer
Gadobutrol-enhanced MRI
Mammography
Lead sponsor: Bayer
Sponsor class: INDUSTRY
First posted: 2010-02-12
Enrollment: 446
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

Brief summary: The purpose of this study is to look at the efficacy (how does it work) and safety of gadobutrol when used for obtaining MR images of both breasts.Women with a recent diagnosis of breast cancer by mammogram (X-ray examination of the breasts) may benefit from MRI of the breasts as MRI may detect additional breast cancers.


Eligibility criteria: Inclusion Criteria:

* Recent histologically proven diagnosis of breast cancer after having obtained X-Ray Mammography (XRM) of both breasts (according to American College of Radiology \[ACR\] and performed no longer than 6 weeks prior to enrollment into the study) and has been referred for a contrast-enhanced Magnetic Resonance Mammography (MRM) prior to surgery of the breast.
* If female, a digital XRM is required if any of the following criteria is met:

  1. patient is younger than 50 years;
  2. patient has heterogeneously or extremely dense breasts;
  3. is not post-menopausal (post-menopause defined as at least 12 months prior to inclusion without menstruation).
* If female of childbearing potential, MRM should be performed on the 7-14th day of the menstrual cycle.
* Has an estimated glomerular filtration rate (eGFR) value \>/= 60 mL/min/1.73m\^2 derived from a serum creatinine result within 2 weeks prior to study enrollment.

Exclusion Criteria:

* Is a female patient who is pregnant or lactating
* Has any contraindication to the MRM examination (e.g. metal implants, phobia) or the use of gadolinium-containing contrast agents.
* Has received any contrast agent within 24 hours prior to the study MRM, or is scheduled to receive any contrast agent within 24 hours after the study MRM.
* Has severe cardiovascular disease (e.g., known long QT syndrome, acute myocardial infarction \[\< 14 days\], unstable angina, congestive heart failure New York Heart Association class IV) or acute stroke (\< 48 hours)).
* Has acute renal insufficiency of any severity due to hepato-renal syndrome or in the peri-operative liver transplantation period or who has acute or chronic moderate or severe renal insufficiency (glomerular filtration rate \< 60 mL/min/1.73m\^2).
* Has received chemotherapy or hormonal therapy for breast cancer within 6 months.
* Has received hormone replacement therapy within 4 weeks prior to study drug administration.
* Is scheduled or likely to require a surgery and/or biopsy in the time period up to 24 hours following study drug application
* Has prior excisional biopsy or breast surgery less than 6 months before enrollment and between XRM and study MRM

Primary outcomes:
measure: Difference for Sensitivity for Detection of Full Extent of Malignant Breast Disease Using CMRM vs UMRM Per Reader
timeFrame: Immediately before injection and after injection
measure: Sensitivity for Detection of Full Extent of Malignant Breast Disease Using CMRM vs UMRM Per Reader
timeFrame: Immediately before injection and after injection
measure: Breast Level Specificity of CMRM for Non-malignant Breasts by Reader
timeFrame: Immediately before injection and after injection
Secondary outcomes:
measure: Breast Level Specificity of CMRM Based on Malignant Breasts
timeFrame: Immediately before injection and after injection
measure: Percentage Difference of Participants Whose Index Cancers Were Detected Using CMRM vs UMRM, CMRM vs XRM, and CMRM vs CMRM+XRM
timeFrame: Immediately before injection and after injection
measure: Percentage Difference of Participants Whose Additional Cancers Were Detected Using CMRM vs UMRM, CMRM vs XRM, and CMRM vs CMRM+XRM
timeFrame: Immediately before injection and after injection
Other outcomes:
measure: Breast Level Specificity for All Breasts by Imaging Modality and by Reader
timeFrame: Immediately before injection and after injection
measure: Categorical Accuracy Difference of Extent of Malignant Disease Verified by SoT by Majority Reader, Breast Region Level
timeFrame: Immediately before injection and after injection
measure: Categorical Accuracy Difference of Extent of Malignant Disease Verified by Histopathology by Majority Reader, Breast Region Level
timeFrame: Immediately before injection and after injection
measure: Sensitivity Difference in the Determination of Malignant Breast Disease Using CMRM vs UMRM, CMRM+XRM vs UMRM+XRM, and CMRM+XRM vs XRM Verified by SoT, Breast Region Level
timeFrame: Immediately before injection and after injection
measure: Sensitivity Difference in the Determination of Unifocal Malignant Breast Disease Using CMRM vs UMRM, CMRM+XRM vs UMRM+XRM, and CMRM+XRM vs XRM Verified by SoT, Breast Region Level
timeFrame: Immediately before injection and after injection
measure: Sensitivity Difference in the Determination of Multifocal Malignant Breast Disease Using CMRM vs UMRM, CMRM+XRM vs UMRM+XRM, and CMRM+XRM vs XRM Verified by SoT, Breast Region Level
timeFrame: Immediately before injection and after injection
measure: Specificity Difference in the Determination of Malignant Breast Disease Using CMRM vs UMRM, CMRM+XRM vs UMRM+XRM, and CMRM+XRM vs XRM Verified by SoT, Breast Region Level
timeFrame: Immediately before injection and after injection
measure: Specificity Difference in the Determination of Unifocal Malignant Breast Disease Using CMRM vs UMRM, CMRM+XRM vs UMRM+XRM, and CMRM+XRM vs XRM Verified by SoT, Breast Region Level
timeFrame: Immediately before injection and after injection
measure: Specificity Difference in the Determination of Multifocal Malignant Breast Disease Using CMRM vs UMRM, CMRM+XRM vs UMRM+XRM, and CMRM+XRM vs XRM Verified by SoT, Breast Region Level
timeFrame: Single examination
measure: Sensitivity Difference of Detection of Multicentric Malignant Disease Verified by SoT by Majority Reader, Breast Level
timeFrame: Immediately before injection and after injection
measure: Accuracy Difference of Presence of Bilateral Malignant Disease Verified by SoT by Majority Reader, Participant Level
timeFrame: Immediately before injection and after injection
measure: Difference of Confidence in Diagnosis for Breast Region Diagnosis Using CMRM vs UMRM, CMRM+XRM vs UMRM+XRM and CMRM+XRM vs XRM by Majority Reader, Participant Level
timeFrame: Immediately before injection and after injection
measure: Blinded Readers: Inter-reader Agreement on Categorical Accuracy Based on Assessment for UMRM vs CMRM - Breast Region Level
timeFrame: Immediately before injection and after injection
measure: Blinded Reader 1: Intra-reader Variability Based on Assessment for CMRM - Breast Level
timeFrame: Immediately before injection and after injection
measure: Blinded Reader 2: Intra-reader Variability Based on Assessment for CMRM - Breast Level
timeFrame: Immediately before injection and after injection
measure: Blinded Reader 3: Intra-reader Variability Based on Assessment for CMRM - Breast Level
timeFrame: Immediately before injection and after injection
measure: Vital Signs Change From Baseline and Follow-up 24 Hours Post Injection - Systolic and Diastolic Blood Pressure
timeFrame: Baseline, Follow-up visit (24 hours post injection)
measure: Vital Signs Change From Baseline and Follow-up 24 Hours Post Injection - Heart Rate
timeFrame: Baseline, Follow-up visit (24 hours post injection)
measure: Number of Participants With at Least One Laboratory Parameter Change From Low or Normal at Baseline to Abnormally High at Follow-up 24 Hours Post Injection
timeFrame: Baseline, Follow-up visit (24 hours post injection)
Locations:
city: La Jolla
country: United States
state: California
city: Los Angeles
country: United States
state: California
city: Newport Beach
country: United States
state: California
city: Washington
country: United States
state: District of Columbia
city: Springfield II
country: United States
state: Illinois
city: Boston
country: United States
state: Massachusetts
city: San Antonio
country: United States
state: Texas
city: Buenos Aires
country: Argentina
state: Ciudad Auton. de Buenos Aires
city: Buenos Aires
country: Argentina
state: Ciudad Auton. de Buenos Aires
city: Buenos Aires
country: Argentina
state: Ciudad Auton. de Buenos Aires
city: São Paulo
country: Brazil
state: Sao Paulo
city: Rio de Janeiro
country: Brazil
city: Sao Paulo
country: Brazil
city: Medellin
country: Colombia
state: Antioquia
city: Bogotá
country: Colombia
state: Cundinamarca
city: Barranquilla
country: Colombia
city: Helsinki
country: Finland
city: Tampere
country: Finland
city: Tübingen
country: Germany
state: Baden-Württemberg
city: Marburg
country: Germany
state: Hessen
city: Hannover
country: Germany
state: Niedersachsen
city: Bielefeld
country: Germany
state: Nordrhein-Westfalen
city: Dortmund
country: Germany
state: Nordrhein-Westfalen
city: Essen
country: Germany
state: Nordrhein-Westfalen
city: Essen
country: Germany
state: Nordrhein-Westfalen
city: Magdeburg
country: Germany
state: Sachsen-Anhalt
city: Lübeck
country: Germany
state: Schleswig-Holstein
city: Potsdam
country: Germany
city: San Donato Milanese
country: Italy
state: Milano
city: Milano
country: Italy
city: Milano
country: Italy
city: Napoli
country: Italy
city: Udine
country: Italy
city: Ansan Si, Kyungki Do
country: Korea, Republic of
city: Seoul
country: Korea, Republic of
city: Seoul
country: Korea, Republic of
city: Seoul
country: Korea, Republic of
city: Chur
country: Switzerland
state: Graubünden
city: Baden
country: Switzerland
city: Bern
country: Switzerland
Study officials:
affiliation: Bayer
name: Bayer Study Director
role: STUDY_DIRECTOR
References:
citation: Endrikat J, Schmidt G, Haverstock D, Weber O, Trnkova ZJ, Barkhausen J. Sensitivity of Contrast-Enhanced Breast MRI vs X-ray Mammography Based on Cancer Histology, Tumor Grading, Receptor Status, and Molecular Subtype: A Supplemental Analysis of 2 Large Phase III Studies. Breast Cancer (Auckl). 2022 Apr 19;16:11782234221092155. doi: 10.1177/11782234221092155. eCollection 2022.
citation: Sardanelli F, Newstead GM, Putz B, Jirakova Trnkova Z, Trimboli RM, Abe H, Haverstock D, Rosenberg M. Gadobutrol-Enhanced Magnetic Resonance Imaging of the Breast in the Preoperative Setting: Results of 2 Prospective International Multicenter Phase III Studies. Invest Radiol. 2016 Jul;51(7):454-61. doi: 10.1097/RLI.0000000000000254.