Primary Brain Tumor
Conditions
Keywords
Primary brain tumor
Brief summary
The purpose of this study is to demonstrate non-inferiority of Dotarem®-enhanced MRI as compared to Gadovist®/ Gadavist®-enhanced MRI in the diagnosis of brain tumors in terms of overall lesion visualization and characterization (off-site assessment). 270 patients will be randomized between 2 arms defining the sequence of administration of the contrast agents at the dose of 0.1mmol/kg, with a minimum of 48 hours and a maximum of 14 days in between. Each patient will, therefore, receive two MRI during his/her participation in the study. The two arms consist in : * Dotarem® in the first MRI, then Gadovist®/Gadavist® in the second MRI. * Gadovist®/Gadavist® in the first MRI, then Dotarem® in the second MRI. Contrast-enhanced MRIs will be performed on 1.5 or 3 Tesla systems. MRI examinations will be evaluated centrally by blinded independent readers for the main evaluation criterion.
Interventions
DRUGDotarem®
Dotarem® 0.1 mmoL/kg (0.2 mL/kg), intravenous (I.V.) bolus.
DRUGGadovist®/Gadavist®
Gadovist®/Gadavist®, 0.1mmol/kg (0.1mL/kg), intravenous (I.V.) bolus.
Sponsors
Guerbet
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
DIAGNOSTIC
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Female or male adult patient (patient having reached legal majority age) * Patient with known or highly suspected primary intracranial tumors (intra-axial or extra-axial) detected by previous CT or MRI examination who are scheduled to undergo a routine contrast-enhanced MRI * Female patient must have effective contraception throughout the study and must have a negative urine pregnancy test at inclusion, or be surgically sterilized, or post-menopausal (minimum 12 months of amenorrhea) * Patient having provided his/her written informed consent to participate in the trial prior to any study-related procedure being conducted * Patient with national health insurance (according to local regulatory requirements)
Exclusion criteria
* Patient with rapidly evolving brain tumor that could change in appearance between the time of the two study MRI examinations. * Patient undergoing current or recent treatment within past 6 weeks or scheduled for any treatment that could results in changes of lesion appearance between the two study examinations. This would include, but not restricted to, the following: current or recent radiation therapy, surgery, starting or recent chemotherapy. * Patient with a contraindication to MRI (e.g., pacemaker, aneurysm clip, severe claustrophobia, infusion pumps, cochlear implants metallic or others according to the imaging site standard practice) * Patient with known severely impaired renal function (defined as eGFR MDRD\< 30 ml/min/1.73m2) * Patient with known Class III/IV congestive heart failure according to the New York Heart Association classification * Patient with known severe adverse drug reaction or contraindication to Gadolinium-Based Contrast Agent * Patient having received any contrast agent within 48 hours prior to first study contrast agent injection scheduled for the study and patient expected to receive any other contrast agent within 24 hours of the last study contrast agent injection * Patient presenting with any condition which, based on the investigator's clinical judgment, would prevent the patient from completing all trial assessments and visits * Patient under guardianship and/or unable or unwilling to cooperate with the requirements of this trial * Pregnant or breast feeding female patient * Patient already included in this trial * Patient included in another clinical trial involving an IMP within 30 days before the first investigational contrast agent injection.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Patients With Overall Lesion Visualization and Characterization Scored as Good or Excellent | Up to 15 days after randomization | Overall lesion visualization and characterization, based on assessment of the primary or largest lesion if there is more than one lesion present, was assessed by 3 independent off-site readers on a 4-point scale: 0\. Poor: does not allow adequate visualization and characterization of the lesion; 1. Fair: allows partial visualization and characterization of the lesion ; 2. Good: allows adequate visualization and characterization of the lesion; 3. Excellent: allows excellent visualization and characterization of the lesion. |
Countries
Colombia, Mexico, South Korea, United States
Participant flow
Recruitment details
Adult patients with known or highly suspected primary intracranial tumors and scheduled for a Dotarem®-enhanced MRI were recruited in 27 active centers in 4 countries (Colombia, South Korea, Mexico and United States) from June 2014 to September 2015.
Pre-assignment details
279 patients signed an informed consent for the study and therefore were considered as included. From these 279 patients, 11 did not receive any injection : 4 for consent withdrawn, 3 for deviation from plan specified in the protocol, 2 for adverse events, 1 at the investigator's discretion and 1 for other reason.
Participants by arm
| Arm | Count |
|---|---|
| Dotarem®/Gadovist® Dotarem®-enhanced MRI, then Gadovist®/Gadavist®-enhanced MRI
Dotarem®: 0.1 mmoL/kg (0.2 mL/kg), intravenous (I.V.) bolus.
Gadovist®/Gadavist®: 0.1mmol/kg (0.1mL/kg), intravenous (I.V.) bolus. | 138 |
| Gadovist®/Dotarem® Gadovist®/Gadavist®-enhanced MRI then Dotarem® enhanced MRI
Dotarem®: 0.1 mmoL/kg (0.2 mL/kg), intravenous (I.V.) bolus.
Gadovist®/Gadavist®: 0.1mmol/kg (0.1mL/kg), intravenous (I.V.) bolus. | 130 |
| Total | 268 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Wash-out (From 2 Days up to 14 Days) | Adverse Event | 1 | 0 |
| Wash-out (From 2 Days up to 14 Days) | other reason | 3 | 2 |
| Wash-out (From 2 Days up to 14 Days) | Protocol Violation | 3 | 3 |
| Wash-out (From 2 Days up to 14 Days) | Withdrawal by Subject | 2 | 5 |
Baseline characteristics
| Characteristic | Total | Dotarem®/Gadovist® | Gadovist®/Dotarem® |
|---|---|---|---|
| Age, Continuous | 53.6 years STANDARD_DEVIATION 15.1 | 52.9 years STANDARD_DEVIATION 15.2 | 54.4 years STANDARD_DEVIATION 15.1 |
| Body Mass Index | 27.66 kg per square metre STANDARD_DEVIATION 5.28 | 27.71 kg per square metre STANDARD_DEVIATION 5.35 | 27.62 kg per square metre STANDARD_DEVIATION 5.23 |
| Gender Female | 172 Participants | 87 Participants | 85 Participants |
| Gender Male | 96 Participants | 51 Participants | 45 Participants |
| Region of Enrollment Colombia | 32 participants | 16 participants | 16 participants |
| Region of Enrollment Korea, Republic of | 47 participants | 24 participants | 23 participants |
| Region of Enrollment Mexico | 103 participants | 52 participants | 51 participants |
| Region of Enrollment United States | 86 participants | 46 participants | 40 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 42 / 258 | 44 / 259 | 63 / 268 |
| serious Total, serious adverse events | 1 / 258 | 0 / 259 | 1 / 268 |
Outcome results
Primary
Percentage of Patients With Overall Lesion Visualization and Characterization Scored as Good or Excellent
Overall lesion visualization and characterization, based on assessment of the primary or largest lesion if there is more than one lesion present, was assessed by 3 independent off-site readers on a 4-point scale: 0\. Poor: does not allow adequate visualization and characterization of the lesion; 1. Fair: allows partial visualization and characterization of the lesion ; 2. Good: allows adequate visualization and characterization of the lesion; 3. Excellent: allows excellent visualization and characterization of the lesion.
Time frame: Up to 15 days after randomization
Population: Patients with at least one valid assessment of the primary outcome and without major protocol deviation
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Gadovist® (Reader 1) | Percentage of Patients With Overall Lesion Visualization and Characterization Scored as Good or Excellent | 94.0 percentage of patients |
| Dotarem® (Reader 1) | Percentage of Patients With Overall Lesion Visualization and Characterization Scored as Good or Excellent | 96.2 percentage of patients |
| Gadovist® (Reader 2) | Percentage of Patients With Overall Lesion Visualization and Characterization Scored as Good or Excellent | 93.2 percentage of patients |
| Dotarem® (Reader 2) | Percentage of Patients With Overall Lesion Visualization and Characterization Scored as Good or Excellent | 90.6 percentage of patients |
| Gadovist® (Reader 3) | Percentage of Patients With Overall Lesion Visualization and Characterization Scored as Good or Excellent | 99.6 percentage of patients |
| Dotarem® (Reader 3) | Percentage of Patients With Overall Lesion Visualization and Characterization Scored as Good or Excellent | 100.0 percentage of patients |