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

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

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.

Study Overview

• Status: Completed
• Conditions: Brain Metastases
• Intervention / Treatment: Drug: Gadobutrol (Gadavist, Gadovist, BAY86-4875); Drug: Gadobutrol (Gadavist, Gadovist, BAY86-4875); Drug: ProHance

• Study Type: Interventional
• Enrollment (Actual): 165
• Phase: Phase 3

Contacts and Locations

Study Locations

• Japan
  • Fukuoka, Japan, 812-8582
  • Osaka, Japan, 558-8558
  • Aichi
    • Nagoya, Aichi, Japan, 464-0021
  • Ehime
    • Matsuyama, Ehime, Japan, 791-0280
  • Fukuoka
    • Kitakyushu, Fukuoka, Japan, 807-8555
  • Hokkaido
    • Sapporo, Hokkaido, Japan, 060-8570
  • Hyogo
    • Kobe, Hyogo, Japan, 650-0047
  • Kanagawa
    • Sagamihara, Kanagawa, Japan, 228-8555
    • Yokohama, Kanagawa, Japan, 222-0036
  • Osaka
    • Habikino, Osaka, Japan, 583-0852
    • Habikino, Osaka, Japan, 583-8588
    • Osakasayama, Osaka, Japan, 589-8511
  • Shizuoka
    • Hamamatsu, Shizuoka, Japan, 430-8558
    • Sunto, Shizuoka, Japan, 411-8777
  • Tokyo
    • Bunkyo-ku, Tokyo, Japan, 113-8655
    • Bunkyo-ku, Tokyo, Japan, 113-8431
    • Chuo-ku, Tokyo, Japan, 104-0045
    • Mitaka, Tokyo, Japan, 181-8611
    • Shinagawa-ku, Tokyo, Japan, 141-0022
  • Tottori
    • Yonago, Tottori, Japan, 683-8504

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: DIAGNOSTIC
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: SINGLE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Gadobutrol 0.1 mmol/kg bw; 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); Gadobutrol enhanced MRI (first injection of gadobutrol 0.1 mmol/kg bw, corresponding to a dose of 0.1 mmol/kg bw); Drug: Gadobutrol (Gadavist, Gadovist, BAY86-4875); Gadobutrol enhanced MRI (second injection of gadobutrol 0.1 mmol/kg bw, corresponding to a total dose of 0.2 mmol/kg bw)
EXPERIMENTAL: Gadobutrol 0.2 mmol/kg bw; 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); Gadobutrol enhanced MRI (first injection of gadobutrol 0.1 mmol/kg bw, corresponding to a dose of 0.1 mmol/kg bw); Drug: Gadobutrol (Gadavist, Gadovist, BAY86-4875); Gadobutrol enhanced MRI (second injection of gadobutrol 0.1 mmol/kg bw, corresponding to a total dose of 0.2 mmol/kg bw)
EXPERIMENTAL: Gadoteridol (ProHance); 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; ProHance enhanced MRI (two injections of gadoteridol 0.1 mmol/kg bw, corresponding to a total dose of 0.2 mmol/kg bw)

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Bayer

Publications and helpful links

General Publications

• Katakami N, Inaba Y, Sugata S, Tsurusaki M, Itoh T, Machida T, Tanaka H, Nakayama T, Morikawa T, Breuer J, Aitoku Y. Magnetic resonance evaluation of brain metastases from systemic malignances with two doses of gadobutrol 1.0 m compared with gadoteridol: a multicenter, phase ii/iii study in patients with known or suspected brain metastases. Invest Radiol. 2011 Jul;46(7):411-8. doi: 10.1097/RLI.0b013e3182145a6c.

Study record dates

Study Major Dates

• Study Start: August 1, 2007
• Primary Completion (ACTUAL): August 1, 2008
• Study Completion (ACTUAL): August 1, 2008

Study Registration Dates

• First Submitted: August 29, 2007
• First Submitted That Met QC Criteria: August 29, 2007
• First Posted (ESTIMATE): August 30, 2007

Study Record Updates

• Last Update Posted (ACTUAL): August 28, 2017
• Last Update Submitted That Met QC Criteria: July 28, 2017
• Last Verified: July 1, 2017

More Information

Terms related to this study

• Keywords: MRI; Imaging; Gadolinium; Brain Metastasis; Diagnostic Agent
• Additional Relevant MeSH Terms: Pathologic Processes; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neoplasms; Neoplasms by Site; Neoplastic Processes; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasm Metastasis; Brain Neoplasms
• Other Study ID Numbers: 91569; 310864 (OTHER: Company internal)