Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Symptoms and General Pathology

Breast Neoplasms

Body Weight

Breast Diseases

Skin Diseases

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.

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

Gadobutrol (Gadavist, Gadovist, BAY86-4875)

Bayer Study Director

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

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

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

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

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.

A malignant breast was defined as FP, when the reader using the respective imaging modality assessed more breast regions as malignant as were present according to SoT. Otherwise the breast was assessed as TN. Specificity was then defined as TN/(TN+FP).

A non-malignant breast was defined as FP when the reader assessed at least one breast region as malignant. A malignant breast was defined as FP, when the reader using the respective imaging modality assessed more breast regions as malignant as were present according to SoT. Otherwise the breast was assessed as TN. Specificity was then defined as (N-FP)/N, where N was total number of breasts.

For a single participant the sensitivity was defined as the proportion of malignant breast regions that were recognized by the reader using the respective imaging modality as malignant. Subsequently the point estimates were calculated based on the mean of the sensitivities across all participants. Regions with malignant disease verified by SoT comprise unifocal and multifocal regions. Difference in sensitivity is calculated as CMRM value minus UMRM value, CMRM+XRM value minus UMRM+XRM value, CMRM+XRM value minus XRM value respectively.

For a single participant the sensitivity was defined as the proportion of malignant breast regions that were recognized by the reader using the respective imaging modality as malignant. Subsequently the point estimates were calculated based on the mean of the sensitivities across all participants. The difference in sensitivity is calculated as CMRM value minus UMRM value, CMRM+XRM value minus UMRM+XRM value, CMRM+XRM value minus XRM value respectively.

A malignant breast was defined as FP, when the reader using the respective imaging modality assessed more breast regions as malignant as were present according to SoT. Otherwise the breast was assessed as TN. Specificity was then defined as TN/(TN+FP). The difference was calculated as CMRM value minus UMRM value, CMRM+XRM value minus UMRM+XRM value, CMRM+XRM value minus XRM value respectively.

For a single participant the sensitivity was defined as the proportion of malignant breast regions that were recognized by the reader using the respective imaging modality as malignant. Subsequently the point estimates were calculated based on the mean of the sensitivities across all participants. The difference was calculated as CMRM value minus UMRM value, CMRM+XRM value minus UMRM+XRM value, CMRM+XRM value minus XRM value respectively.

The disease state "bilateral malignant disease" was derived from the assessment of the different regions for each breast (right and left) for investigators for each imaging modality (UMRM, CMRM, XRM, UMRM+XRM, and CMRM+XRM) based on the following rule: If the participant had at least one breast with no malignant region , the assessment of bilateral malignant disease was categorized as "No". If the participant had at least one malignant lesion in both breasts, the assessment of bilateral malignant disease was categorized as "Yes". The proportion of correct matches of each different image set to the SoT for the existence of bilateral malignant disease were derived. The analysis was based on the difference in accuracy for the evaluation of bilateral malignant disease for the following image comparisons on a participant level. The difference was calculated as CMRM value minus UMRM value, CMRM+XRM value minus UMRM+XRM value, CMRM+XRM value minus XRM value respectively.

Inter-reader agreement was assessed by considering each breast region to have 2 possibilities (malignant disease / no malignant disease) for an assessment by the 2 image sets (UMRM and CMRM). Kappa value varies from 0 (no agreement) to 1 (perfect agreement).

Intra-reader variability was assessed using a kappa on the match to SoT for the different regions within each participant (match, no match SoT). For each of the 3 readers, intra-reader agreement was assessed by considering each breast region to have 2 possibilities for an assessment by CMRM: matched SoT or did not match SoT. Kappa value varies from 0 (no agreement) to 1 (perfect agreement).

Systolic and diastolic blood pressure were measured in a supine position. Blood pressure was not to be measured on the arm used for the injection.

Heart rate was measured in a supine position.

Number of participants with at least one occurrence of changing from low or normal at baseline to high at follow-up.

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).

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.

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.

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.

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.

Bayer

Participants 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 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.

Gadobutrol (Gadavist, BAY86-4875)

Participants 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 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.

Age, Continuous

Sex: Female, Male

White

Asian

Black

American Indian/Alaska Native

Missing

Race/Ethnicity, Customized

Argentina

Canada

Germany

Spain

India

Poland

Taiwan

United States

Country

Therapeutic Area Head

Reader 1

Reader 2

Reader 3

Investigator

CMRM Versus UMRM

The analyses were based on 390 participants in the Full Analysis Set (FAS) who had regions with malignant disease verified by Standard of Truth (SoT).

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

CMRM

UMRM

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

The analyses were based on 367 participants in FAS; evaluable for specificity were breasts without malignant disease as verified by Standard of Truth (SoT) for which a CMRM assessment was available.

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

The analyses were based on 390 participants in FAS; evaluable for specificity were breasts with malignant disease verified by SoT for which an assessment by the imaging modality was available.

Breast Level Specificity of CMRM Based on Malignant Breasts

CMRM vs XRM

CMRM vs CMRM+XRM

The analyses were based on 388 participants in FAS; index cancer was defined as the cancer confirmed by histology prior to inclusion which made the participant eligible for the study.

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

The evaluation was based on the 84 participants in the FAS who had at least one additional cancer region according to SoT.

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

CMRM+XRM vs UMRM+XRM

CMRM+XRM vs XRM

All participants in the FAS with assessments for this outcome 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

X-ray Mammography (XRM)

CMRM+XRM

UMRM+XRM

The analyses were performed for a total number of 390 participants who had regions with malignant disease verified by SoT with available assessment by the imaging modality.

Sensitivity for Detection of Full Extent of Malignant Breast Disease Using XRM, CMRM+XRM and UMRM+XRM Per Reader

The analyses were based on 367 participants; evaluable for specificity were breasts with no malignant disease verified by SoT for which an assessment of the imaging modality was available.

Breast Level Specificity of in Non-malignant Breasts Using UMRM, XRM, CMRM+XRM and UMRM+XRM by Reader

The analyses were based on 390 participants; evaluable for specificity were breasts with malignant disease verified by SoT for which an assessment by the imaging modality was available.

Breast Level Specificity in Malignant Breasts Using UMRM, XRM, CMRM+XRM and UMRM+XRM by Reader

The analyses were based on 395 participants in FAS; evaluable for specificity were breasts with or without malignant disease verified by SoT with available assessments by the imaging modality.

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

CMRM vs UMRM

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

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

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

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

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

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

Sensitivity of Detection of Multicentric Malignant Disease Verified by SoT, Breast Level

The analyses were based on 380 participants in FAS; evaluable subjects with at least one region verified by SoT in each breast with available CMRM, UMRM, CMRM+XRM, UMRM+XRM and XRM assessment.

Accuracy Difference of Presence of Bilateral Malignant Disease Verified by SoT by Clinical Investigator, Participant Level

Blinded Readers: Inter-reader Agreement on Sensitivity Based on Assessment for UMRM vs CMRM - Breast Region Level

All participants in the FAS with assessments for this outcome measure.

Blinded Reader 1: Intra-reader Variability Based on Assessment for CMRM - Breast Level

Blinded Reader 2: Intra-reader Variability Based on Assessment for CMRM - Breast Level

Blinded Reader 3: Intra-reader Variability Based on Assessment for CMRM - Breast Level

The Statistical Analysis Plan (SAP) amendment re-defined study objectives and replaced protocol-defined parameters such as categorical accuracy prior to database closure and breaking the blind. The SAP amendment is based upon review of results of an identical clinical study within the "GEMMA" program and also includes advice from the FDA.

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

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

Systolic blood pressure

Diastolic blood pressure

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 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.

Safety Analysis Set (SAF): The analysis of safety data was performed using all available data from all participants who administered any amount of gadobutrol.

Vital Signs Change From Baseline and Follow-up 24 Hours Post Injection - Systolic and Diastolic Blood Pressure

Vital Signs Change From Baseline and Follow-up 24 Hours Post Injection - Heart Rate

Hematology

Clinical chemistry

Urinalysis

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

Participants 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.

Spots Global Cancer Trial Database for Efficacy and Safety of Gadobutrol 1.0 Molar (Gadovist) for Breast Magnetic Resonance Imaging (MRI)

Trial Identification

Conditions

Interventions

Study Description

Keywords

Eligibility

Locations

Contact Details

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