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Breast CancerPhase 3GEMMA 2NCT01104584

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

A Phase 3 study testing Gadobutrol (Gadavist, Gadovist, BAY86-4875) in people with Breast Cancer, run by Bayer at 48 sites in 9 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Breast Cancer
What is being tested?
Gadobutrol (Gadavist, Gadovist, BAY86-4875)
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
460 participants
Where
48 sitesin 9 countries
Study dates
May 2010to Jan 2012
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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.
Show all 9Show fewer
  • 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

Trial locations and contacts

48 sites in 9 countries.

48 sites in 9 countries

Germany11 sites

  • Study site

    Berlin, 10115

  • Study site

    Bochum, North Rhine-Westphalia, 44892

  • Study site

    Erlangen, Bavaria, 91054

  • Study site

    Frankfurt am Main, Hesse, 60596

  • Study site

    Gera, Thuringia, 07548

  • Study site

    Göttingen, Lower Saxony, 37081

  • Study site

    Göttingen, Lower Saxony, 37099

  • Study site

    Greifswald, Mecklenburg-Vorpommern, 17489

  • Study site

    München, Bavaria, 81377

  • Study site

    Münster, North Rhine-Westphalia, 48145

  • Study site

    Münster, North Rhine-Westphalia, 48149

Other trials in Germany

United States9 sites

  • Study site

    Chicago, Illinois, 60637

  • Study site

    Columbus, Ohio, 43212

  • Study site

    Englewood, Colorado, 80112

  • Study site

    New York, New York, 10065

  • Study site

    Oakland, California, 94609

  • Study site

    Providence, Rhode Island, 02903

  • Study site

    San Antonio, Texas, 78229

  • Study site

    Tacoma, Washington, 98321

  • Study site

    Tucson, Arizona, 85724

Other trials in United States

Poland5 sites

  • Study site

    Bydgoszcz, 85-796

  • Study site

    Gliwice, 44-100

  • Study site

    Krakow, 30-501

  • Study site

    Szczecin, 70-111

  • Study site

    Warsaw, 02-781

Other trials in Poland

Spain5 sites

  • Study site

    Alzira, Valencia

  • Study site

    Barcelona, Barcelona, 08036

  • Study site

    Córdoba, 14004

  • Study site

    Girona, Girona, 17002

  • Study site

    Sabadell, Barcelona, 08208

Other trials in Spain

Taiwan5 sites

  • Study site

    Taichung

  • Study site

    Taipei, Taiwan, 100

  • Study site

    Taipei, 110

  • Study site

    Taipei, 114

  • Study site

    Taizung, 402

Other trials in Taiwan

Canada4 sites

  • Study site

    Hamilton, Ontario, L8N 4A6

  • Study site

    Montreal, Quebec, H4J 1C5

  • Study site

    Toronto, Ontario, M5G 2M9

  • Study site

    Toronto, Ontario, M5S 1B2

Other trials in Canada

Argentina3 sites

  • Study site

    Buenos Aires, Ciudad Auton. de Buenos Aires, C1082A

  • Study site

    Buenos Aires, Ciudad Auton. de Buenos Aires, C1181ACH

  • Study site

    Buenos Aires, Ciudad Auton. de Buenos Aires, C1425BEE

Other trials in Argentina

India3 sites

  • Study site

    Delhi, 110085

  • Study site

    Mumbai, Maharashtra, 400012

  • Study site

    Mumbai, 400 004

Other trials in India

Netherlands3 sites

  • Study site

    Eindhoven, EJ, 5623

  • Study site

    Maastricht, 6229 HX

  • Study site

    Nijmegen, 6525 GA

Other trials in Netherlands

About this study

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

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
Being tested
Gadobutrol (Gadavist, Gadovist, BAY86-4875)
Keywords
Breast Cancer, Gadobutrol-enhanced MRI, Mammography, Diagnostic Imaging
Medical subject headings
Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

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

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

Study groups in NCT01104584
Study groupRoleWhat they receive
Gadobutrol (Gadavist, BAY86-4875)ExperimentalPatients 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.
Receives: Drug: Gadobutrol (Gadavist, Gadovist, BAY86-4875)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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).

    Measured: Immediately before injection and after injection

  2. 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.

    Measured: Immediately before injection and after injection

  3. 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.

    Measured: Immediately before injection and after injection

Secondary outcomes (4)

  1. Breast Level Specificity of CMRM Based on Malignant Breasts

    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).

    Measured: Immediately before injection and after injection

  2. 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.

    Measured: Immediately before injection and after injection

  3. 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.

    Measured: Immediately before injection and after injection

  4. 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.

    Measured: Immediately before injection and after injection

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted15 Apr 2010 (estimated)
  2. Study startMay 2010
  3. Primary completionSep 2011
  4. Study completionJan 2012

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Diagnosis
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
460 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01104584
Sponsor's protocol ID
91782
Other IDs
2009-009598-90, 2009
Acronym
GEMMA 2
Status last verified
Nov 2014
First submitted
14 Apr 2010
Last updated
11 Nov 2014
Data monitoring committee
No

Publications

  • 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.

    PubMed 35462754

  • 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.

    PubMed 26840494

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Gadobutrol (Gadavist, Gadovist, BAY86-4875) in people with Breast Cancer, run by Bayer at 48 sites in 9 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 11 Nov 2014. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 48 sites in Germany, United States, Poland, Spain, Taiwan and 4 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 11 Nov 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Difference of Sensitivity for Detection of Full Extent of Malignant Breast Disease Using CMRM vs UMRM Per Reader (time frame: Immediately before injection and after injection). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01104584, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Nov 2014.

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