Diagnostic contribution of XENETIX® CT PERFUSION in pre-therapeutical assessment of hepatocellular carcinoma.

• Register: EUCTR
• Last refreshed on: 24 November 2014
• Main ID: EUCTR2011-002609-31-AT
• Date of registration: 24/10/2011
• Prospective Registration: Yes
• Primary sponsor: Guerbet
• Public title: Diagnostic contribution of XENETIX® CT PERFUSION in pre-therapeutical assessment of hepatocellular carcinoma.
• Scientific title: Diagnostic contribution of XENETIX® CT PERFUSION in pre-therapeutical assessment of hepatocellular carcinoma. - Hepatic CT perfusion
• Date of first enrolment: 23/11/2011
• Target sample size: 83
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2011-002609-31
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: no Open: no Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: no

Countries of recruitment

Austria, Germany, Korea, Republic of, Switzerland

Contacts

• Name: Clinical Project Manager
• Affiliation: Guerbet

• Name: Clinical Project Manager
• Affiliation: Guerbet

Key inclusion & exclusion criteria

Inclusion criteria:
- Male and female adult subjects (having reached legal majority age– 18 years old for European subjects, 20 years old for Korean subjects).

- Subjects diagnosed for HCC and planned for surgery (tumorectomy, sectionectomy, segmentectomy, lobectomy or transplantation) within a timeframe of 30 days between first imaging procedure used for the study and surgery.

- Female subjects must be surgically sterilized, or post-menopausal (minimum 12 months of amenorrhea) or must have a documented negative urine pregnancy test at screening.

- Subjects able to understand and having provided their written informed consent to participate in the trial.

- Subjects with health insurance (according to the local regulatory requirements)

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 68
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 15

Exclusion criteria:
- Subjects who have undergone prior TACE (TransArterial Chemo Embolization), prior RFA (Radio Frequency Ablation) or prior SIRT (Selected Internal Radio Therapy) within two years before inclusion.

- Subjects with known severe adverse drug reaction or contraindication to the investigational product.

- Subjects having received any MR or X-Ray contrast medium within 24 hours prior to administration of investigational product.

- Subjects presenting with known severe renal failure (elevated serum creatinine (>1.5 mg/dl or >120µmol/l) or estimated creatinine clearance < 30 ml/min as calculated by the Cockcroft and Gault formula or e-GFR < 30ml/min/1.73m²)

- Any condition which, based on the investigator's clinical judgement, would prevent the subjects from completing all trial assessments and visits (e.g.: mental or physical incapacity, language comprehension, geographical localisation, etc…).

- Subjects under guardianship and/or inability or unwillingness to cooperate with the requirements of this trial.

- Breast feeding or pregnant subjects.

- Subjects previously included in this trial.

- Subjects having participated in any investigational drug study within 30 days prior the study inclusion or already included in another clinical trial involving an Investigational Medicinal Product (IMP).



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Diagnosis [E01]

Subjects diagnosed for HCC and planned for surgery (tumorectomy, sectionectomy, segmentectomy, lobectomy or transplantation).
MedDRA version: 16.0 Level: LLT Classification code 10019830 Term: Hepatocellular carcinoma resectable System Organ Class: 100000004864

Intervention(s)

Trade Name: XENETIX 350
Product Name: Xenetix 350
Pharmaceutical Form: Solution for injection
INN or Proposed INN: IOBITRIDOL
CAS Number: 136949-58-1
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 767.8-

Primary Outcome(s)

Main Objective: To prospectively determine the diagnostic value of Xenetix®-CT perfusion for the discrimination between well-differentiated HCC and moderately/poorly differentiated HCC (off-site assessment). Histopathology will be used as the gold standard for the evaluation of HCC grading

Secondary Objective: (1) To evaluate diagnostic value of Xenetix®-CT perfusion for the discrimination between well-differentiated HCC and moderately/poorly differentiated HCC (on-site assessment)

(2) To evaluate the correlation between CT perfusion parameters (on-site and off-site assessments) and:- histopathology data for HCC disease- - vascular invasion according to histopathology - AFP levels- mid-term outcomes of subjects with HCC after a one year follow-up from surgery

(3) To compare CT perfusion, triple phase CT and MRI images in terms of:- number of lesions - localization of lesions- size of lesions- characterization of lesions- Sensitivity, specificity , positive and negative predictive values for HCC detection and characterization

(4) To evaluate the feasibility of a CT perfusion protocol and data post-processing in clinical routine.

(5) To assess the clinical tolerance of Xenetix 350 during and immediately after the CT perfusion examination.

Timepoint(s) of evaluation of this end point: Visit: CT perfusion imaging
Histology assessment

Primary end point(s): The primary endpoint is the measurement of 3 CT perfusion parameters (BV, BF and PS) in 2 groups of tumors: well differentiated tumors and moderately/poorly differentiated tumors.
The average response level of each perfusion parameter will be computed in the 2 tumor groups. Depending on the parameter, the 2 groups will be compared according to the following statistical hypotheses:

Statistical hypotheses
Differences between means will be tested using Student's t-test according to the following item:
m1i is the expected average of parameter i for the moderately/poorly-differentiated tumor group;
m2i is the expected average of parameter i for the well-differentiated tumor group;
Di = m2i – m1i is the difference between both groups of tumor for parameter i;
si is the expected common standard deviation for parameter i.

Null hypothesis H0:
(No difference between the 2 tumor groups)
Di = 0; type one-error a = 0.025/3 and si are expected around 107, 5 and 13 respectively for BF, BV and PS (according to Sahani et al.vii).

Alternative hypothesis H1:
(Differences between the 2 tumor groups)
Di > 0; type two-error b = 0.06 and 0.18

Both on-site and off-site assessments of the CT perfusion and histological parameters are performed, only off-site assessments will be taken into account for the primary analysis.

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: Imaging visit (CT perfusion, MRI and CT)
Histology assessment
1-year follow-up

Secondary end point(s): From the intervention phase trial:
· On-site evaluation of primary criterion.

· Agreement between CT perfusion measurements (BV, BF, PS and ALP, PVP, TLP and HPI) and histopathology findings will be assessed. Histological findings taken into account here are the TNM classification and the following immunohistochemistry parameters HCC phenotype (Glypican-3, HSP70, Glutamine synthetase), microvessel density (CD-31) and angiogenic factors (H1F1alpha, CA-9). Means of each perfusion parameters will be computed within TNM categories or immunohistochemistry grading levels (<10%, 10-50%, >50%) and compared through analyses of variance (parameters in TNM) and regression analyses (parameters in grading scales).

· Agreement between CT perfusion measurements and vascular invasion (histologically proven) will be assessed. Perfusion parameter means will be computed for subjects with and without vascular invasion. Difference between the 2 groups will be tested using Student’s t-test.

· Agreement between CT perfusion measurements and fibrosis and necrosis level will be assessed through linear and non-linear regression analyses.

· Agreement between CT perfusion measurements and AFP level will be assessed through linear and non-linear regression analyses.

· CT perfusion, CE-CT and MRI examinations will be compared for the number of additional foci/lesion(s) observed and their location. The analysis of variance will be used for testing average number of lesion and the Chi square for testing the independence between imaging examinations and location of lesions.

· Sensitivity, specificity, positive and negative predictive values of CT perfusion, contrast enhanced-CT (CE-CT) for HCC detection and characterization will be assessed using MRI findings as reference technique.


From the observation phase trial:

· The relation between the different perfusion parameters and surgery follow-up will be explored, taken into account the disease evolution and the subject management after one year: disease evolution will be classified as progression of the disease, stabilization or regression, and subject management with different treatments. The average of perfusion parameters will be computed in each groups and compared through analyses of variance.

· Agreement between CT perfusion measurements and AFP level at one-year will be assessed through linear and non-linear regression analyses.


Both on-site and off-site assessments of the CT perfusion parameters are performed and taken into account for the secondary analysis.

Secondary ID(s)

ISO-44-013

2011-002609-31-DE

Source(s) of Monetary Support

Guerbet