SH L 562BB Phase II/III Dose Justification and Gadoteridol-controlled Comparative Study

Study Overview
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Brief Summary
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This study is conducted to compare the contrast effect and safety of SH L562BB with ProHance, which has already been approved as a pharmaceutical product of similar indication.

Official Title
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Multi-center, Randomized, Controlled, Single-blind, Intra-individual Comparisons of 2 Dose of Gadobutrol 1.0 Molar and Gadoteridol (ProHance) Crossover Studies With Corresponding Blinded Image Evaluation Following Multiple Injections of 0.1 mmol/kg bw of Gadobutrol and Gadoteridol in Patients With Known or Suspected Brain Metastasis

Conditions
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Brain Metastases

Intervention / Treatment
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* Drug: Gadobutrol (Gadavist, Gadovist, BAY86-4875)
* Drug: Gadobutrol (Gadavist, Gadovist, BAY86-4875)
* Drug: ProHance


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Japanese patients at least 20 years of age Patients with diagnosed primary cancer Patients with metastatic lesions by CT/MRI Exclusion Criteria: Patients who have contraindication to the MRI examinations Patients who have severe renal disorder Patients in extremely serious general condition

Ages Eligible for Study
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Minimum Age: 20 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Gadobutrol 0.1 mmol/kg bw<br>Participants received first injection (intravenous [i.v.]) of gadobutrol 0.1 mmol/kg body weight (bw), corresponding to a dose of 0.1 mmol/kg bw | Drug: Gadobutrol (Gadavist, Gadovist, BAY86-4875)<br>* Gadobutrol enhanced MRI (first injection of gadobutrol 0.1 mmol/kg bw, corresponding to a dose of 0.1 mmol/kg bw)<br>|
| Experimental: Gadobutrol 0.2 mmol/kg bw<br>Participants received second injection (i.v.) of gadobutrol 0.1 mmol/kg bw, corresponding to a total dose of 0.2 mmol/kg bw. The interval of two bolus injections is 13-15 min | Drug: Gadobutrol (Gadavist, Gadovist, BAY86-4875)<br>* Gadobutrol enhanced MRI (second injection of gadobutrol 0.1 mmol/kg bw, corresponding to a total dose of 0.2 mmol/kg bw)<br>|
| Experimental: Gadoteridol (ProHance)<br>Participants received two injections (i.v.) of gadoteridol 0.1 mmol/kg bw, corresponding to a total dose of 0.2 mmol/kg bw. The interval of two bolus injections is 13-15 min | Drug: ProHance<br>* ProHance enhanced MRI (two injections of gadoteridol 0.1 mmol/kg bw, corresponding to a total dose of 0.2 mmol/kg bw)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Lesions Detected by Blinded Readers (BR) and Investigator | Number of metastatic lesions (unenhanced and enhanced) per participant detected on postcontrast Magnetic resonance (MR) images by averaged blinded reader and investigator | one day | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Score of Visibility Assessment - Degree of Lesion Contrast Enhancement by Blinded Reader | Degree of contrast enhancement for each lesion on postcontrast MR images using the 4-point scale by averaged blinded reader (Score 1=No, 2=Moderate, 3=Good, 4=Excellent) | one day | 
| Score of Visibility Assessment - Degree of Lesion Contrast Enhancement by Investigator | Degree of contrast enhancement for each lesion on postcontrast MR images using the 4-point scale by investigator (Score 1=No, 2=Moderate, 3=Good, 4=Excellent) | one day | 
| Score of Visibility Assessment - Border Delineation by Blinded Reader | Border delineation for each lesion on postcontrast MR images using the 4-point scale by averaged blinded reader (Score 1=None, 2=Moderate, 3=Good, 4=Excellent) | one day | 
| Score of Visibility Assessment - Border Delineation by Investigator | Border delineation for each lesion on postcontrast MR images using the 4-point scale by investigator (Score 1=None, 2=Moderate, 3=Good, 4=Excellent) | one day | 
| Treatment Planning Confidence - Gadobutrol 0.1 mmol/kg bw vs. Gadoteridol (ProHance) 0.2 mmol/kg bw by Treatment Planning Experts (TPE) | Treatment planning confidence evaluated separately for each image set (gadobutrol [Gado-] 0.1 mmol/kg bw and gadoteridol [Pro-] 0.2 mmol/kg) by TPE (category: not confident, confident, and not assessable) | one day | 
| Treatment Planning Confidence - Gadobutrol 0.1 mmol/kg bw vs. Gadoteridol (ProHance) 0.2 mmol/kg bw by Investigator | Treatment planning confidence evaluated separately for each image set (gadobutrol 0.1 mmol/kg bw and gadoteridol 0.2 mmol/kg) by investigator (category: not confident, confident, and not assessable) | one day | 
| Treatment Planning Confidence - Gadobutrol 0.2 mmol/kg bw vs. Gadoteridol (ProHance) 0.2 mmol/kg bw by TPE | Treatment planning confidence evaluated separately for each image set (gadobutrol 0.2 mmol/kg bw and gadoteridol 0.2 mmol/kg) by TPE (category: not confident, confident, and not assessable) | one day | 
| Treatment Planning Confidence - Gadobutrol 0.2 mmol/kg bw vs. Gadoteridol (ProHance) 0.2 mmol/kg bw by Investigator | Treatment planning confidence evaluated separately for each image set (gadobutrol 0.2 mmol/kg bw and gadoteridol 0.2 mmol/kg) by investigator (category: not confident, confident, and not assessable) | one day | 
| Number of Participants With Performance in Stereotactic Radiosurgery (SRS) Planning by TPE | Comparison of overall image quality for SRS treatment planning between gadobutrol and gadoteridol by TPE | one day | 
| Number of Participants With Performance in Stereotactic Radiosurgery (SRS) Planning by Investigator | Comparison of overall image quality for SRS treatment planning between gadobutrol and gadoteridol by investigator | one day | 
| Number of Participants With Reasons for Performance in SRS Planning by TPE | Reasons for comparison results of overall image quality for SRS treatment planning between gadobutrol and gadoteridol by investigator (multiple answers applicable) | one day | 
| Number of Participants With Reasons for Performance in SRS Planning by Investigator | Reasons for comparison results of overall image quality for SRS treatment planning between gadobutrol and gadoteridol by investigator (multiple answers applicable) | one day | 
| Lesion Size Evaluated by Independent Radiologist | Size of each lesion on postcontrast MR images evaluated by independent radiologist (mean and standard deviation of 603 lesions) | one day | 
| Contrast Noise Ratio (CNR) of Lesions Evaluated by Independent Radiologist | CNR of lesion/normal white matter based on the signal intensity of MR images evaluated by independent radiologist (mean and standard deviation of 306 lesions) | one day | 
| Intraclass Correlation Coefficient (ICC) Among 3 Blinded Readers on the Number of Detected Lesions | ICC among 3 blinded readers calculated for number of detected lesions using the statistical model with two random effects, i.e., blinded readers and individual patients. | one day | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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MRI, Brain Metastasis, Gadolinium, Imaging, Diagnostic Agent