Efficacy and Safety of Gadobutrol 1.0 Molar (Gadovist) for Breast MRI

NCT01067976 | Completed Phase 3 Results

• 3 other identifiers: 91743GEMMA 12009-009597-27
• Study Type: interventional
• Target: 446
• Locations: 9 countries
• Sites: 40

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.

Conditions

Breast Cancer; Diagnostic Imaging

Keywords

Breast Cancer; Gadobutrol-enhanced MRI; Mammography

Outcome Measures

Primary Outcomes (3)

• Difference for Sensitivity for Detection of Full Extent of Malignant Breast Disease Using CMRM vs UMRM Per Reader

  For a single participant the sensitivity was defined as the proportion of malignant breast regions that were recognized by the clinical investigators and the 3 blinded readers using the respective imaging modality as malignant. Subsequently the sensitivity percentage was calculated based on the mean of the sensitivities across all participants. The difference was calculated as CMRM value minus UMRM value. For ease of expression, the following abbreviations will be used: Magnetic Resonance Mammography (MRM), Unenhanced MRM (UMRM), combined unenhanced and contrast (gadobutrol)-enhanced MRM (CMRM), X-ray mammography (XRM).

  Immediately before injection and after injection

• Sensitivity for Detection of Full Extent of Malignant Breast Disease Using CMRM vs UMRM Per Reader

  For a single participant the sensitivity was defined as the proportion of malignant breast regions that were recognized by the clinical investigators and the 3 blinded readers using the respective imaging modality as malignant. Subsequently the sensitivity percentage was calculated based on the mean of the sensitivities across all participants.

  Immediately before injection and after injection

• Breast Level Specificity of CMRM for Non-malignant Breasts by Reader

  A non-malignant breast was defined as false positive (FP), when the reader assessed at least one breast region as malignant. When all breast regions were assessed as non-malignant, the breast was defined as true negative (TN). Breast level specificity was first defined in participant as number of TN-breasts in participant divided by number of non-malignant breasts in participant. Subsequently the specificity percentage was calculated based on the mean of the specificities across all participants who contributed with at least one non-malignant breast.

  Immediately before injection and after injection

Secondary Outcomes (3)

• Breast Level Specificity of CMRM Based on Malignant Breasts

  Immediately before injection and after injection

• Percentage Difference of Participants Whose Index Cancers Were Detected Using CMRM vs UMRM, CMRM vs XRM, and CMRM vs CMRM+XRM

  Immediately before injection and after injection

• Percentage Difference of Participants Whose Additional Cancers Were Detected Using CMRM vs UMRM, CMRM vs XRM, and CMRM vs CMRM+XRM

  Immediately before injection and after injection

Other Outcomes (19)

• Breast Level Specificity for All Breasts by Imaging Modality and by Reader

  Immediately before injection and after injection

• Categorical Accuracy Difference of Extent of Malignant Disease Verified by SoT by Majority Reader, Breast Region Level

  Immediately before injection and after injection

• Categorical Accuracy Difference of Extent of Malignant Disease Verified by Histopathology by Majority Reader, Breast Region Level

  Immediately before injection and after injection

Study Arms (1)

Gadobutrol (Gadavist, BAY86-4875)

EXPERIMENTAL

Patients first received an unenhanced MRM, followed by a gadobutrol-enhanced MRM. Gadobutrol was administered at the standard dose of 0.1 mmol/kg bw \[0.1 ml/kg bw\] as an intravenous injection (i.v.) injection at a rate of 2 ml/sec. UMRM and CMRM image sets were evaluated in a randomized fashion. After the evaluation of the UMRM or CMRM the respective XRM was added and evaluated together with the UMRM images.

Drug: Gadobutrol (Gadavist, Gadovist, BAY86-4875)

Interventions

Gadobutrol (Gadavist, Gadovist, BAY86-4875) DRUG

A single bolus injection of gadobutrol 1.0 M 0.1mmol/kg body weight

Gadobutrol (Gadavist, BAY86-4875)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• patient is younger than 50 years;
• patient has heterogeneously or extremely dense breasts;
• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Bayer: lead

Study Sites (40)

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La Jolla, California, 92093, United States

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Los Angeles, California, 90033, United States

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Newport Beach, California, 92658-6100, United States

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Washington D.C., District of Columbia, 20007-2197, United States

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Springfield II, Illinois, 62781, United States

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Boston, Massachusetts, 02118, United States

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San Antonio, Texas, 78229, United States

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Buenos Aires, Ciudad Auton. de Buenos Aires, C1082A, Argentina

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Buenos Aires, Ciudad Auton. de Buenos Aires, C1181ACH, Argentina

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Buenos Aires, Ciudad Auton. de Buenos Aires, C1425BEE, Argentina

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Rio de Janeiro, Rio de Janeiro, 22649, Brazil

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São Paulo, São Paulo, 05651-901, Brazil

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São Paulo, Brazil

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Medellín, Antioquia, Colombia

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Bogotá, Cundinamarca, Colombia

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Barranquilla, Colombia

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Helsinki, 00180, Finland

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Tampere, 33521, Finland

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Tübingen, Baden-Wurttemberg, 72076, Germany

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Marburg, Hesse, 35033, Germany

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Hanover, Lower Saxony, 30625, Germany

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Bielefeld, North Rhine-Westphalia, Germany

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Dortmund, North Rhine-Westphalia, 44263, Germany

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Essen, North Rhine-Westphalia, 45147, Germany

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Essen, North Rhine-Westphalia, 45257, Germany

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Magdeburg, Saxony-Anhalt, 39120, Germany

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Lübeck, Schleswig-Holstein, 23538, Germany

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Potsdam, 14467, Germany

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San Donato Milanese, Milano, 20097, Italy

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Milan, 20132, Italy

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Milan, 20141, Italy

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Napoli, 80131, Italy

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Udine, 33100, Italy

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Ansan Si, Kyungki Do, 425-021, South Korea

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Seoul, 135-710, South Korea

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Seoul, 138-736, South Korea

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Seoul, 150-713, South Korea

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Bern, Canton of Bern, 3010, Switzerland

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Chur, Kanton Graubünden, 7000, Switzerland

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Baden, 5404, Switzerland

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Related Publications (2)

• 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.

  PMID: 35462754 DERIVED

• 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.

  PMID: 26840494 DERIVED

Related Links

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MeSH Terms

Conditions

Breast Neoplasms

Interventions

gadobutrol

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Results Point of Contact

• Title: Therapeutic Area Head
• Organization: BAYER

clinical-trials-contact@bayerhealthcare.com

Study Officials

• Bayer Study Director

  Bayer

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 11, 2010
• First Posted: February 12, 2010
• Study Start: February 1, 2010
• Primary Completion: July 1, 2011
• Study Completion: January 1, 2012
• Last Updated: November 11, 2014
• Results First Posted: November 11, 2014

Record last verified: 2014-11

Locations

BR (3); FI (2); US (7); KR (4); AR (3); IT (5); CH (3); CO (3); DE (10)