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Efficacy and Safety of Gadobutrol 1.0 Molar (Gadovist) for Breast Magnetic Resonance Imaging (MRI) (GEMMA 2)

Primary Purpose

Breast Cancer

Status

Completed

Phase

Phase 3

Locations

International

Study Type

Interventional

Intervention

Gadobutrol (Gadavist, Gadovist, BAY86-4875)

About this trial

This is an interventional diagnostic trial for Breast Cancer focused on measuring Breast Cancer, Gadobutrol-enhanced MRI, Mammography, Diagnostic Imaging

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Gadobutrol (Gadavist, BAY86-4875)

Arm Description

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

Outcomes

Primary Outcome Measures

Difference of 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).

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

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.

Secondary Outcome Measures

Breast Level Specificity of CMRM Based on Malignant Breasts

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

Index cancer was defined as the cancer confirmed by histology prior to inclusion which made the participants eligible for the study. The difference in percentage of participants was calculated as CMRM value minus UMRM value, CMRM value minus XRM value, CMRM value minus CMRM+XRM value respectively.

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

Additional cancer was defined as cancer which was present according to SoT, but which was not defined as index cancer, i.e. was not known when the participant was enrolled into the study. The difference in percentage of participants was calculated as CMRM value minus UMRM value, CMRM value minus XRM value, CMRM value minus CMRM+XRM value respectively.

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

The investigator and the blinded readers each recorded his/her confidence in diagnosis for each breast region based on a 4-point scale (1 = not confident, 2 = somewhat confident, 3 = confident, and 4 = very confident). For each participant, the mean of the confidence responses for the diagnosed breast regions was calculated, and rounded to the nearest 0.5. The difference was calculated as CMRM value minus UMRM value, CMRM+XRM value minus UMRM+XRM value, CMRM+XRM value minus XRM value respectively.

Full Information

NCT ID

NCT01104584

First Posted

April 14, 2010

Last Updated

November 10, 2014

Sponsor

Bayer

1. Study Identification

Unique Protocol Identification Number

NCT01104584

Brief Title

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

Acronym

GEMMA 2

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

2. Study Status

Record Verification Date

November 2014

Overall Recruitment Status

Completed

Study Start Date

May 2010 (undefined)

Primary Completion Date

September 2011 (Actual)

Study Completion Date

January 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Bayer

4. Oversight

Data Monitoring Committee

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Breast Cancer

Keywords

Breast Cancer, Gadobutrol-enhanced MRI, Mammography, Diagnostic Imaging

7. Study Design

Primary Purpose

Diagnostic

Study Phase

Phase 3

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

460 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Gadobutrol (Gadavist, BAY86-4875)

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

Gadobutrol (Gadavist, Gadovist, BAY86-4875)

Intervention Description

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

Primary Outcome Measure Information:

Title

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

Description

Time Frame