Clinical trial NCT01104584: Efficacy and Safety of Gadobutrol 1.0 Molar (Gadovist) for Breast Magnetic Resonance Imaging (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
Keywords: Breast Cancer
Gadobutrol-enhanced MRI
Mammography
Diagnostic Imaging
Lead sponsor: Bayer
Sponsor class: INDUSTRY
First posted: 2010-04-15
Enrollment: 460
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
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:

  * a. patient is younger than 50 years;
  * b. patient has heterogeneously or extremely dense breasts;
  * c. 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 of 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 Index Cancers Were Detected Using CMRM vs UMRM, CMRM vs XRM, and CMRM vs CMRM+XRM
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 Reader, Participant Level
timeFrame: Immediately before injection and after injection
Other outcomes:
measure: Sensitivity for Detection of Full Extent of Malignant Breast Disease Using XRM, CMRM+XRM and UMRM+XRM Per Reader
timeFrame: Immediately before injection and after injection
measure: Breast Level Specificity of in Non-malignant Breasts Using UMRM, XRM, CMRM+XRM and UMRM+XRM by Reader
timeFrame: Immediately before injection and after injection
measure: Breast Level Specificity in Malignant Breasts Using UMRM, XRM, CMRM+XRM and UMRM+XRM by Reader
timeFrame: Immediately before injection and after injection
measure: Breast Level Specificity for All Breasts by Imaging Modality and by Reader
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: Immediately before injection and after injection
measure: Sensitivity of Detection of Multicentric Malignant Disease Verified by SoT, Breast Level
timeFrame: Immediately before injection and after injection
measure: Accuracy Difference of Presence of Bilateral Malignant Disease Verified by SoT by Clinical Investigator, Participant Level
timeFrame: Immediately before injection and after injection
measure: Blinded Readers: Inter-reader Agreement on Sensitivity 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: 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: Vital Signs Change From Baseline and Follow-up 24 Hours Post Injection - Systolic and Diastolic Blood Pressure
timeFrame: Baseline, 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: Tucson
country: United States
state: Arizona
city: Oakland
country: United States
state: California
city: Englewood
country: United States
state: Colorado
city: Chicago
country: United States
state: Illinois
city: New York
country: United States
state: New York
city: Columbus
country: United States
state: Ohio
city: Providence
country: United States
state: Rhode Island
city: San Antonio
country: United States
state: Texas
city: Tacoma
country: United States
state: Washington
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: Hamilton
country: Canada
state: Ontario
city: Toronto
country: Canada
state: Ontario
city: Toronto
country: Canada
state: Ontario
city: Montreal
country: Canada
state: Quebec
city: Erlangen
country: Germany
state: Bayern
city: München
country: Germany
state: Bayern
city: Frankfurt
country: Germany
state: Hessen
city: Greifswald
country: Germany
state: Mecklenburg-Vorpommern
city: Göttingen
country: Germany
state: Niedersachsen
city: Göttingen
country: Germany
state: Niedersachsen
city: Bochum
country: Germany
state: Nordrhein-Westfalen
city: Münster
country: Germany
state: Nordrhein-Westfalen
city: Münster
country: Germany
state: Nordrhein-Westfalen
city: Gera
country: Germany
state: Thüringen
city: Berlin
country: Germany
city: Mumbai
country: India
state: Maharashtra
city: Delhi
country: India
city: Mumbai
country: India
city: Eindhoven
country: Netherlands
state: EJ
city: Maastricht
country: Netherlands
city: Nijmegen
country: Netherlands
city: Bydgoszcz
country: Poland
city: Gliwice
country: Poland
city: Krakow
country: Poland
city: Szczecin
country: Poland
city: Warszawa
country: Poland
city: Sabadell
country: Spain
state: Barcelona
city: Alzira
country: Spain
state: Valencia
city: Barcelona
country: Spain
city: Cordoba
country: Spain
city: Girona
country: Spain
city: Taichung
country: Taiwan
city: Taipei
country: Taiwan
city: Taipei
country: Taiwan
city: Taipei
country: Taiwan
city: Taizung
country: Taiwan
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.