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

• Sponsor: Bayer
• Information provided by (Responsible Party): Bayer

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Brain Metastases	Drug: Gadobutrol (Gadavist, Gadovist, BAY86-4875); Drug: ProHance	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 165 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Single (Participant)
• Primary Purpose: Diagnostic
• Official Title: 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
• Study Start Date: August 2007
• Actual Primary Completion Date: August 2008
• Actual Study Completion Date: August 2008

Arms and Interventions

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)
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 (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)

Outcome Measures

Primary Outcome Measures :

1. Number of Lesions Detected by Blinded Readers (BR) and Investigator [ Time Frame: one day ]
   Number of metastatic lesions (unenhanced and enhanced) per participant detected on postcontrast Magnetic resonance (MR) images by averaged blinded reader and investigator

Secondary Outcome Measures :

1. Score of Visibility Assessment - Degree of Lesion Contrast Enhancement by Blinded Reader [ Time Frame: one day ]
   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)
2. Score of Visibility Assessment - Degree of Lesion Contrast Enhancement by Investigator [ Time Frame: one day ]
   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)
3. Score of Visibility Assessment - Border Delineation by Blinded Reader [ Time Frame: one day ]
   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)
4. Score of Visibility Assessment - Border Delineation by Investigator [ Time Frame: one day ]
   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)
5. Treatment Planning Confidence - Gadobutrol 0.1 mmol/kg bw vs. Gadoteridol (ProHance) 0.2 mmol/kg bw by Treatment Planning Experts (TPE) [ Time Frame: one day ]
   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)
6. Treatment Planning Confidence - Gadobutrol 0.1 mmol/kg bw vs. Gadoteridol (ProHance) 0.2 mmol/kg bw by Investigator [ Time Frame: one day ]
   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)
7. Treatment Planning Confidence - Gadobutrol 0.2 mmol/kg bw vs. Gadoteridol (ProHance) 0.2 mmol/kg bw by TPE [ Time Frame: one day ]
   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)
8. Treatment Planning Confidence - Gadobutrol 0.2 mmol/kg bw vs. Gadoteridol (ProHance) 0.2 mmol/kg bw by Investigator [ Time Frame: one day ]
   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)
9. Number of Participants With Performance in Stereotactic Radiosurgery (SRS) Planning by TPE [ Time Frame: one day ]
   Comparison of overall image quality for SRS treatment planning between gadobutrol and gadoteridol by TPE
10. Number of Participants With Performance in Stereotactic Radiosurgery (SRS) Planning by Investigator [ Time Frame: one day ]
    Comparison of overall image quality for SRS treatment planning between gadobutrol and gadoteridol by investigator
11. Number of Participants With Reasons for Performance in SRS Planning by TPE [ Time Frame: one day ]
    Reasons for comparison results of overall image quality for SRS treatment planning between gadobutrol and gadoteridol by investigator (multiple answers applicable)
12. Number of Participants With Reasons for Performance in SRS Planning by Investigator [ Time Frame: one day ]
    Reasons for comparison results of overall image quality for SRS treatment planning between gadobutrol and gadoteridol by investigator (multiple answers applicable)
13. Lesion Size Evaluated by Independent Radiologist [ Time Frame: one day ]
    Size of each lesion on postcontrast MR images evaluated by independent radiologist (mean and standard deviation of 603 lesions)
14. Contrast Noise Ratio (CNR) of Lesions Evaluated by Independent Radiologist [ Time Frame: one day ]
    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)
15. Intraclass Correlation Coefficient (ICC) Among 3 Blinded Readers on the Number of Detected Lesions [ Time Frame: one day ]
    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.

Eligibility Criteria

• Ages Eligible for Study: 20 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Locations

Japan

Nagoya, Aichi, Japan, 464-0021

Matsuyama, Ehime, Japan, 791-0280

Kitakyushu, Fukuoka, Japan, 807-8555

Sapporo, Hokkaido, Japan, 060-8570

Kobe, Hyogo, Japan, 650-0047

Sagamihara, Kanagawa, Japan, 228-8555

Yokohama, Kanagawa, Japan, 222-0036

Habikino, Osaka, Japan, 583-0852

Habikino, Osaka, Japan, 583-8588

Osakasayama, Osaka, Japan, 589-8511

Hamamatsu, Shizuoka, Japan, 430-8558

Sunto, Shizuoka, Japan, 411-8777

Bunkyo-ku, Tokyo, Japan, 113-8431

Bunkyo-ku, Tokyo, Japan, 113-8655

Chuo-ku, Tokyo, Japan, 104-0045

Mitaka, Tokyo, Japan, 181-8611

Shinagawa-ku, Tokyo, Japan, 141-0022

Yonago, Tottori, Japan, 683-8504

Fukuoka, Japan, 812-8582

Osaka, Japan, 558-8558

Sponsors and Collaborators

Bayer

Investigators

• Study Director: Bayer Study Director; Bayer

More Information

Publications of Results:

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.

• Responsible Party: Bayer
• ClinicalTrials.gov Identifier: NCT00522951 History of Changes
• Other Study ID Numbers: 91569; 310864 ( Other Identifier: Company internal )
• First Posted: August 30, 2007
• Results First Posted: August 3, 2011
• Last Update Posted: August 28, 2017
• Last Verified: July 2017

Keywords provided by Bayer:

MRI; Brain Metastasis; Gadolinium; Imaging; Diagnostic Agent

Additional relevant MeSH terms:

Neoplasm Metastasis; Brain Neoplasms; Neoplastic Processes; Neoplasms; Pathologic Processes; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases