Breast CancerPhase 3NCT01067976
Efficacy and Safety of Gadobutrol 1.0 Molar (Gadovist) for Breast MRI
A Phase 3 study testing Gadobutrol (Gadavist, Gadovist, BAY86-4875) in people with Breast Cancer and Diagnostic Imaging, run by Bayer at 40 sites in 9 countries.
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, Diagnostic Imaging
- 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
- 446 participants
- Where
- 40 sitesin 9 countries
- Study dates
- Feb 2010to Jan 2012
- Phase
- Phase 3
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:
- patient is younger than 50 years;
- patient has heterogeneously or extremely dense breasts;
- 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.
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- 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
40 sites in 9 countries.
40 sites in 9 countries
Germany10 sites
Study site
Bielefeld, North Rhine-Westphalia
Study site
Dortmund, North Rhine-Westphalia, 44263
Study site
Essen, North Rhine-Westphalia, 45147
Study site
Essen, North Rhine-Westphalia, 45257
Study site
Hanover, Lower Saxony, 30625
Study site
Lübeck, Schleswig-Holstein, 23538
Study site
Magdeburg, Saxony-Anhalt, 39120
Study site
Marburg, Hesse, 35033
Study site
Potsdam, 14467
Study site
Tübingen, Baden-Wurttemberg, 72076
United States7 sites
Study site
Boston, Massachusetts, 02118
Study site
La Jolla, California, 92093
Study site
Los Angeles, California, 90033
Study site
Newport Beach, California, 92658-6100
Study site
San Antonio, Texas, 78229
Study site
Springfield II, Illinois, 62781
Study site
Washington D.C., District of Columbia, 20007-2197
Italy5 sites
Study site
Milan, 20132
Study site
Milan, 20141
Study site
Naples, 80131
Study site
San Donato Milanese, Milano, 20097
Study site
Udine, 33100
South Korea4 sites
Study site
Ansan Si, Kyungki Do, 425-021
Study site
Seoul, 135-710
Study site
Seoul, 138-736
Study site
Seoul, 150-713
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
Brazil3 sites
Study site
Rio de Janeiro, Rio de Janeiro, 22649
Study site
São Paulo, São Paulo, 05651-901
Study site
São Paulo
Colombia3 sites
Study site
Barranquilla
Study site
Bogotá, Cundinamarca
Study site
Medellín, Antioquia
Switzerland3 sites
Study site
Baden, 5404
Study site
Bern, Canton of Bern, 3010
Study site
Chur, Kanton Graubünden, 7000
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, Diagnostic Imaging
- Being tested
- Gadobutrol (Gadavist, Gadovist, BAY86-4875)
- Keywords
- Breast Cancer, Gadobutrol-enhanced MRI, Mammography
- 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 0.1mmol/kg body weight
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Gadobutrol (Gadavist, Gadovist, BAY86-4875) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: 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.
Measured: 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.
Measured: Immediately before injection and after injection
Secondary outcomes (3)
Breast Level Specificity of CMRM Based on Malignant Breasts
A malignant breast was defined as false positive (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 true negative (TN). Specificity was then defined as TN/(TN+FP).
Measured: 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
Index cancer is 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
Percentage Difference of Participants Whose Additional 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
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Feb 2010 (estimated)
- Study startFeb 2010
- Primary completionJul 2011
- Study completionJan 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Breast CancerStudies of the same condition, open and under way.
- More trials run by BayerThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 446 participants (actual)
Sponsor and investigators
- Lead sponsor
- Bayer
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Bayer Study Director, Study director, Bayer
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01067976
- Sponsor's protocol ID
- 91743
- Other IDs
- GEMMA 1, 2009-009597-27, 2009
- Status last verified
- Nov 2014
- First submitted
- 11 Feb 2010
- Last updated
- 11 Nov 2014
- Results posted
- Yes, on ClinicalTrials.gov
- 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 35462754Sardanelli 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