Trial Outcomes & Findings for Hepatic Xenetix-CT Perfusion (NCT NCT01639703)

NCT ID: NCT01639703

Last Updated: 2017-07-13

Results Overview

The mean level of each CT perfusion parameter was compared between well differentiated and moderately/poorly differentiated lesions according to WHO classification evaluated off-site.

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 96 participants
• Primary outcome timeframe: Within a week from CT perfusion to surgery
• Results posted on: 2017-07-13

Participant Flow

A total of 96 patients were enrolled in 4 countries: Austria, Germany, South Korea and Switzerland.

Participant milestones

Measure	CT Perfusion Xenetix-CT perfusion imaging: Injection of 50 ml of Xenetix
Overall Study STARTED	96
Overall Study COMPLETED	84
Overall Study NOT COMPLETED	12

Reasons for withdrawal

Measure	CT Perfusion Xenetix-CT perfusion imaging: Injection of 50 ml of Xenetix
Overall Study Withdrawal by Subject	5
Overall Study Other reason	7

Baseline Characteristics

For one patient, the gender was missing.

Baseline characteristics by cohort

Measure	All Included Patients n=96 Participants All patients included in the study.
Age, Continuous	56.2 years STANDARD_DEVIATION 11.2 • n=96 Participants
Sex: Female, Male Female	22 Participants n=95 Participants • For one patient, the gender was missing.
Sex: Female, Male Male	73 Participants n=95 Participants • For one patient, the gender was missing.
Region of Enrollment Austria	3 participants n=96 Participants
Region of Enrollment Korea, Republic of	85 participants n=96 Participants
Region of Enrollment Switzerland	6 participants n=96 Participants
Region of Enrollment Germany	2 participants n=96 Participants
Severity of cirrhosis (Child-Pugh score) Class A	79 Participants n=96 Participants
Severity of cirrhosis (Child-Pugh score) Class B	8 Participants n=96 Participants
Severity of cirrhosis (Child-Pugh score) Class C	2 Participants n=96 Participants

PRIMARY outcome

Timeframe: Within a week from CT perfusion to surgery

Population: A total of 77 patients were analyzed for CT perfusion parameters: 38 had lesions assessed as "well differentiated", 42 had lesions assessed as "moderately/poorly differentiated" and 3 had lesions assessed as "well differentiated" and "moderately/poorly differentiated".

The mean level of each CT perfusion parameter was compared between well differentiated and moderately/poorly differentiated lesions according to WHO classification evaluated off-site.

Outcome measures

Measure	Well Differentiated Lesions n=47 lesions Among the 90 lesions analyzed for CT perfusion parameters, 47 were well differentiated according to WHO classification.	Moderately/Poorly Differentiated Lesions n=43 lesions Among the 90 lesions analyzed, 43 were moderately or poorly differentiated according to WHO classification.	Glutamine Synthetase 10-50% Quantification of glutamine synthetase labelling from 10 to 50%	Glutamine Synthetase >50% Quantification of glutamine synthetase labelling greater than 50%
Blood Volume (BV) According to Degree of Lesions Differentiation	15.930 mL/100 grams Standard Deviation 6.663	13.958 mL/100 grams Standard Deviation 5.315	—	—

PRIMARY outcome

Timeframe: Within a week from CT perfusion to surgery

Population: A total of 77 patients were analyzed for CT perfusion parameters: 38 had lesions assessed as "well differentiated", 42 had lesions assessed as "moderately/poorly differentiated" and 3 had lesions assessed as "well differentiated" and "moderately/poorly differentiated".

The mean level of each CT perfusion parameter was compared between well differentiated and moderately/poorly differentiated lesions according to WHO classification evaluated off-site.

Outcome measures

Measure	Well Differentiated Lesions n=47 lesions Among the 90 lesions analyzed for CT perfusion parameters, 47 were well differentiated according to WHO classification.	Moderately/Poorly Differentiated Lesions n=43 lesions Among the 90 lesions analyzed, 43 were moderately or poorly differentiated according to WHO classification.	Glutamine Synthetase 10-50% Quantification of glutamine synthetase labelling from 10 to 50%	Glutamine Synthetase >50% Quantification of glutamine synthetase labelling greater than 50%
Blood Flow (BF) According to Degree of Lesions Differentiation	73.042 mL/100 grams/min Standard Deviation 21.551	72.051 mL/100 grams/min Standard Deviation 31.792	—	—

PRIMARY outcome

Timeframe: Within a week from CT perfusion to surgery

Population: A total of 77 patients were analyzed for CT perfusion parameters: 38 had lesions assessed as "well differentiated", 42 had lesions assessed as "moderately/poorly differentiated" and 3 had lesions assessed as "well differentiated" and "moderately/poorly differentiated".

The mean level of each CT perfusion parameter was compared between well differentiated and moderately/poorly differentiated lesions according to WHO classification evaluated off-site.

Outcome measures

Measure	Well Differentiated Lesions n=47 lesions Among the 90 lesions analyzed for CT perfusion parameters, 47 were well differentiated according to WHO classification.	Moderately/Poorly Differentiated Lesions n=43 lesions Among the 90 lesions analyzed, 43 were moderately or poorly differentiated according to WHO classification.	Glutamine Synthetase 10-50% Quantification of glutamine synthetase labelling from 10 to 50%	Glutamine Synthetase >50% Quantification of glutamine synthetase labelling greater than 50%
Permeability Surface (PS) According to Degree of Lesions Differentiation	26.421 mL/100 grams/min Standard Deviation 10.014	27.750 mL/100 grams/min Standard Deviation 9.425	—	—

SECONDARY outcome

Timeframe: Within a week from CT perfusion to surgery

Population: A total of 77 patients were analyzed for CT perfusion parameters: 38 had lesions assessed as "well differentiated", 42 had lesions assessed as "moderately/poorly differentiated" and 3 had lesions assessed as "well differentiated" and "moderately/poorly differentiated".

The mean level of each CT perfusion parameter was compared between well differentiated and moderately/poorly differentiated lesions according to WHO classification evaluated off-site.

Outcome measures

Measure	Well Differentiated Lesions n=47 lesions Among the 90 lesions analyzed for CT perfusion parameters, 47 were well differentiated according to WHO classification.	Moderately/Poorly Differentiated Lesions n=43 lesions Among the 90 lesions analyzed, 43 were moderately or poorly differentiated according to WHO classification.	Glutamine Synthetase 10-50% Quantification of glutamine synthetase labelling from 10 to 50%	Glutamine Synthetase >50% Quantification of glutamine synthetase labelling greater than 50%
Arterial Liver Perfusion (ALP) According to Degree of Lesions Differentiation	43.234 mL/min/100 mL Standard Deviation 16.989	42.967 mL/min/100 mL Standard Deviation 16.678	—	—

SECONDARY outcome

Timeframe: Within a week from CT perfusion to surgery

Population: A total of 77 patients were analyzed for CT perfusion parameters: 38 had lesions assessed as "well differentiated", 42 had lesions assessed as "moderately/poorly differentiated" and 3 had lesions assessed as "well differentiated" and "moderately/poorly differentiated".

The mean level of each CT perfusion parameter was compared between well differentiated and moderately/poorly differentiated lesions according to WHO classification evaluated off-site.

Outcome measures

Measure	Well Differentiated Lesions n=47 lesions Among the 90 lesions analyzed for CT perfusion parameters, 47 were well differentiated according to WHO classification.	Moderately/Poorly Differentiated Lesions n=43 lesions Among the 90 lesions analyzed, 43 were moderately or poorly differentiated according to WHO classification.	Glutamine Synthetase 10-50% Quantification of glutamine synthetase labelling from 10 to 50%	Glutamine Synthetase >50% Quantification of glutamine synthetase labelling greater than 50%
Portal Venous Liver Perfusion (PVP) According to Degree of Lesions Differentiation	19.492 mL/min/100 mL Standard Deviation 14.586	13.708 mL/min/100 mL Standard Deviation 13.207	—	—

SECONDARY outcome

Timeframe: Within a week from CT perfusion to surgery

Population: A total of 77 patients were analyzed for CT perfusion parameters: 38 had lesions assessed as "well differentiated", 42 had lesions assessed as "moderately/poorly differentiated" and 3 had lesions assessed as "well differentiated" and "moderately/poorly differentiated".

The mean level of each CT perfusion parameter was compared between well differentiated and moderately/poorly differentiated lesions according to WHO classification evaluated off-site.

TLP = ALP + PVP

Outcome measures

Measure	Well Differentiated Lesions n=47 lesions Among the 90 lesions analyzed for CT perfusion parameters, 47 were well differentiated according to WHO classification.	Moderately/Poorly Differentiated Lesions n=43 lesions Among the 90 lesions analyzed, 43 were moderately or poorly differentiated according to WHO classification.	Glutamine Synthetase 10-50% Quantification of glutamine synthetase labelling from 10 to 50%	Glutamine Synthetase >50% Quantification of glutamine synthetase labelling greater than 50%
Total Liver Perfusion (TLP) According to Degree of Lesions Differentiation	62.725 mL/min/100 mL Standard Deviation 15.620	56.674 mL/min/100 mL Standard Deviation 20.494	—	—

SECONDARY outcome

Timeframe: Within a week from CT perfusion to surgery

Population: A total of 77 patients were analyzed for CT perfusion parameters: 38 had lesions assessed as "well differentiated", 42 had lesions assessed as "moderately/poorly differentiated" and 3 had lesions assessed as "well differentiated" and "moderately/poorly differentiated".

The mean level of each CT perfusion parameter was compared between well differentiated and moderately/poorly differentiated lesions according to WHO classification evaluated off-site.

Outcome measures

Measure	Well Differentiated Lesions n=47 lesions Among the 90 lesions analyzed for CT perfusion parameters, 47 were well differentiated according to WHO classification.	Moderately/Poorly Differentiated Lesions n=43 lesions Among the 90 lesions analyzed, 43 were moderately or poorly differentiated according to WHO classification.	Glutamine Synthetase 10-50% Quantification of glutamine synthetase labelling from 10 to 50%	Glutamine Synthetase >50% Quantification of glutamine synthetase labelling greater than 50%
Hepatic Perfusion Index (HPI) According to Degree of Lesions Differentiation	75.232 percentage Standard Deviation 18.458	80.834 percentage Standard Deviation 14.503	—	—

SECONDARY outcome

Timeframe: Within a week from CT perfusion to surgery

Population: A total of 77 patients were analyzed for CT perfusion and immunohistochemistry parameters. A patient could have several lesions in different groups: 3 patients presented at least 1 lesion in group10-50% and another lesion in group \>50%; 2 patients presented at least 1 lesion in group \>50% and 1 missing data; 2 patients presented missing data.

Glutamine synthetase is an immunohistochemistry parameter of hepatocellular carcinoma phenotype.

Glutamine synthetase labelling was quantified and in case of positive quantification, classified in the following categories: 1-10%, 10-50% and >50%. In case of absence of glutamine synthetase labelling, lesions were classified in the "glutamine synthetase 0%" category.

Outcome measures

Measure	Well Differentiated Lesions n=6 lesions Among the 90 lesions analyzed for CT perfusion parameters, 47 were well differentiated according to WHO classification.	Moderately/Poorly Differentiated Lesions Among the 90 lesions analyzed, 43 were moderately or poorly differentiated according to WHO classification.	Glutamine Synthetase 10-50% n=17 lesions Quantification of glutamine synthetase labelling from 10 to 50%	Glutamine Synthetase >50% n=62 lesions Quantification of glutamine synthetase labelling greater than 50%
Blood Volume According to Immunohistochemistry Parameter (Glutamine Synthetase)	14.994 mL/100 grams Standard Deviation 5.714	—	12.964 mL/100 grams Standard Deviation 5.268	15.551 mL/100 grams Standard Deviation 6.328

SECONDARY outcome

Timeframe: Within a week from CT perfusion to surgery

Population: A total of 77 patients were analyzed for CT perfusion and immunohistochemistry parameters. A patient could have several lesions.

CD31 is an immunohistochemistry marker of microvessel density. CD31 labelling was quantified and in case of positive quantification, classified in the following categories: 1-10%, 10-50% and >50%. In case of absence of CD31 labelling, lesions were classified in the "CD31 0%" category.

Outcome measures

Measure	Well Differentiated Lesions Among the 90 lesions analyzed for CT perfusion parameters, 47 were well differentiated according to WHO classification.	Moderately/Poorly Differentiated Lesions n=39 lesions Among the 90 lesions analyzed, 43 were moderately or poorly differentiated according to WHO classification.	Glutamine Synthetase 10-50% n=45 lesions Quantification of glutamine synthetase labelling from 10 to 50%	Glutamine Synthetase >50% Quantification of glutamine synthetase labelling greater than 50%
Blood Volume According to Immunohistochemistry Parameter (CD31)	—	14.708 mL/100 grams Standard Deviation 7.657	15.589 mL/100 grams Standard Deviation 4.561	—

SECONDARY outcome

Timeframe: Within a week from CT perfusion to surgery

Population: A total of 77 patients were analyzed for CT perfusion and immunohistochemistry parameters. A patient could have several lesions in different groups: 3 patients presented at least 1 lesion in group10-50% and another lesion in group \>50%; 2 patients presented at least 1 lesion in group \>50% and 1 missing data; 2 patients presented missing data.

Glutamine synthetase is an immunohistochemistry parameter of hepatocellular carcinoma phenotype.

Glutamine synthetase labelling was quantified and in case of positive quantification, classified in the following categories: 1-10%, 10-50% and >50%. In case of absence of glutamine synthetase labelling, lesions were classified in the "glutamine synthetase 0%" category.

Outcome measures

Measure	Well Differentiated Lesions n=6 lesions Among the 90 lesions analyzed for CT perfusion parameters, 47 were well differentiated according to WHO classification.	Moderately/Poorly Differentiated Lesions Among the 90 lesions analyzed, 43 were moderately or poorly differentiated according to WHO classification.	Glutamine Synthetase 10-50% n=17 lesions Quantification of glutamine synthetase labelling from 10 to 50%	Glutamine Synthetase >50% n=62 lesions Quantification of glutamine synthetase labelling greater than 50%
Blood Flow According to Immunohistochemistry Parameter (Glutamine Synthetase)	79.178 mL/100 grams/min Standard Deviation 32.656	—	61.804 mL/100 grams/min Standard Deviation 22.087	74.261 mL/100 grams/min Standard Deviation 27.619

SECONDARY outcome

Timeframe: Within a week from CT perfusion to surgery

Population: A total of 77 patients were analyzed for CT perfusion and immunohistochemistry parameters. A patient could have several lesions.

CD31 is an immunohistochemistry marker of microvessel density. CD31 labelling was quantified and in case of positive quantification, classified in the following categories: 1-10%, 10-50% and >50%. In case of absence of CD31 labelling, lesions were classified in the "CD31 0%" category.

Outcome measures

Measure	Well Differentiated Lesions Among the 90 lesions analyzed for CT perfusion parameters, 47 were well differentiated according to WHO classification.	Moderately/Poorly Differentiated Lesions n=39 lesions Among the 90 lesions analyzed, 43 were moderately or poorly differentiated according to WHO classification.	Glutamine Synthetase 10-50% n=45 lesions Quantification of glutamine synthetase labelling from 10 to 50%	Glutamine Synthetase >50% Quantification of glutamine synthetase labelling greater than 50%
Blood Flow According to Immunohistochemistry Parameter (CD31)	—	70.057 mL/100 grams/min Standard Deviation 25.317	75.206 mL/100 grams/min Standard Deviation 28.519	—

SECONDARY outcome

Timeframe: Within a week from CT perfusion to surgery

Population: A total of 77 patients were analyzed for CT perfusion and immunohistochemistry parameters. A patient could have several lesions in different groups: 3 patients presented at least 1 lesion in group10-50% and another lesion in group \>50%; 2 patients presented at least 1 lesion in group \>50% and 1 missing data; 2 patients presented missing data.

Glutamine synthetase is an immunohistochemistry parameter of hepatocellular carcinoma phenotype.

Glutamine synthetase labelling was quantified and in case of positive quantification, classified in the following categories: 1-10%, 10-50% and >50%. In case of absence of glutamine synthetase labelling, lesions were classified in the "glutamine synthetase 0%" category.

Outcome measures

Measure	Well Differentiated Lesions n=6 lesions Among the 90 lesions analyzed for CT perfusion parameters, 47 were well differentiated according to WHO classification.	Moderately/Poorly Differentiated Lesions Among the 90 lesions analyzed, 43 were moderately or poorly differentiated according to WHO classification.	Glutamine Synthetase 10-50% n=17 lesions Quantification of glutamine synthetase labelling from 10 to 50%	Glutamine Synthetase >50% n=62 lesions Quantification of glutamine synthetase labelling greater than 50%
Permeability Surface According to Immunohistochemistry Parameter (Glutamine Synthetase)	28.896 mL/100 grams/min Standard Deviation 7.207	—	24.840 mL/100 grams/min Standard Deviation 6.769	27.139 mL/100 grams/min Standard Deviation 10.714

SECONDARY outcome

Timeframe: Within a week from CT perfusion to surgery

Population: A total of 77 patients were analyzed for CT perfusion and immunohistochemistry parameters. A patient could have several lesions.

CD31 is an immunohistochemistry marker of microvessel density. CD31 labelling was quantified and in case of positive quantification, classified in the following categories: 1-10%, 10-50% and >50%. In case of absence of CD31 labelling, lesions were classified in the "CD31 0%" category.

Outcome measures

Measure	Well Differentiated Lesions Among the 90 lesions analyzed for CT perfusion parameters, 47 were well differentiated according to WHO classification.	Moderately/Poorly Differentiated Lesions n=39 lesions Among the 90 lesions analyzed, 43 were moderately or poorly differentiated according to WHO classification.	Glutamine Synthetase 10-50% n=45 lesions Quantification of glutamine synthetase labelling from 10 to 50%	Glutamine Synthetase >50% Quantification of glutamine synthetase labelling greater than 50%
Permeability Surface According to Immunohistochemistry Parameter (CD31)	—	25.434 mL/100 grams/min Standard Deviation 9.721	28.587 mL/100 grams/min Standard Deviation 9.832	—

Adverse Events

Safety Set

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Safety Set n=84 participants at risk All included patients receiving at least one injection of Xenetix, regardless of the quantity. This set was used for safety analyses.
Gastrointestinal disorders Nausea	2.4% 2/84 • Number of events 2 • Adverse events were recorded during and immediately after the CT perfusion examination over a 30 min follow up period.
Infections and infestations Pneumonia	1.2% 1/84 • Number of events 1 • Adverse events were recorded during and immediately after the CT perfusion examination over a 30 min follow up period.
Skin and subcutaneous tissue disorders Pruritus	1.2% 1/84 • Number of events 1 • Adverse events were recorded during and immediately after the CT perfusion examination over a 30 min follow up period.
Skin and subcutaneous tissue disorders Urticaria	1.2% 1/84 • Number of events 1 • Adverse events were recorded during and immediately after the CT perfusion examination over a 30 min follow up period.

Additional Information

Corinne Dubourdieu, PharmD, Head of Clinical Projects and Medical Writing

Guerbet

Phone: +33 (0) 1 45 91 50 00

Email: corinne.dubourdieu@guerbet-group.com

Results disclosure agreements

• Principal investigator is a sponsor employee All written or oral papers and publications must have the joint agreement of the investigator and the sponsor. Each investigator agrees not to publish/submit/present the results of the study main criterion involving only the patients he/she has included. Any abstract project will be first submitted to Guerbet at least 10 working days before submission to the congress scientific committee.
• Publication restrictions are in place

Restriction type: OTHER