DCE-MRI Using Dotarem® in Evaluation of Therapeutic Response to Sorafenib in Patients With Advanced Stage HCC

Study Overview
=================
Brief Summary
-----------------
The main objective is to evaluate the value of dynamic contrast-enhanced Magnetic Resonance Imaging (DCE-MRI) in prediction of response of patients with hepatocellular carcinoma (HCC) to treatment with Sorafenib assessed by mRECIST.

Detailed Description
-----------------
One of the secondary objectives was to evaluate the correlation between DCE-MRI perfusion parameters at baseline and: Overall Survival (OS) Progression-Free Survival (PFS) Time to Progression (TTP) Three DCE-MRI examinations were done during the study: at the enrolment and initiation of the sorafenib treatment one week after initiation of the sorafenib treatment two weeks after initiation of the sorafenib treatment DCE-MRI perfusion parameters were assessed by a centralized radiologist at baseline (corresponding to the day of enrolment and initiation of Sorafenib treatment), week 1 and week 2. According to mRECIST criteria, HCC lesions were evaluated on computed tomography images by two on-site radiologists at the time of enrolment and 8 weeks later (2 months). OS, PFS and TTP were calculated from survival and tumor progression data recorded one year after initiation of the sorafenib treatment.

Official Title
-----------------
Phase IV Study of DCE-MRI Using Dotarem® in Evaluation of Therapeutic Response to Sorafenib in Patients With Advanced Stage HCC

Conditions
-----------------
Hepatocellular Carcinoma

Intervention / Treatment
-----------------
* Drug: Gadoterate meglumine


Participation Criteria
=================
Eligibility Criteria
-----------------
Male and female adult patients (age ≥ 20 years old) Patients diagnosed with unresectable HCC [Child Pugh class A and major vascular invasion, extrahapatic metastasis, or progression after transarterial chemoembolization more than 2 times] Presence of mRECIST target lesion within liver [lesion which can be classified as a RECIST measurable lesion (can be measured ≥ 1 cm in at least one dimension), lesion suitable for repeated measure, lesion showing intraluminal arterial enhancement on contrast-enhanced CT or MRI] Patients planned to be treated with sorafenib Patient with liver CT performed or planned to be performed within 4 weeks before initiation of sorafenib treatment Patient with a life expectancy of 12 weeks or more No previous treatment with sorafenib Female patients who are surgically sterilized, or post-menopausal (minimum 12 months of amenorrhea) or who have a documented negative urine hCG test at screening

Ages Eligible for Study
-----------------
Minimum Age: 20 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Diagnostic
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Gadoterate meglumine<br>there is one single arm of patients (no comparative arm) | Drug: Gadoterate meglumine<br>* Gadoterate meglumine was administered at a dose of 0.1 mmol/kg (0.2 mL/kg) using a power injector, in an intravenous bolus at a rate of 3 mL/sec.<br>* Other names: Dotarem;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Correlation Coefficient Between DCE-MRI Perfusion Parameters and the Response of Target Lesions to Sorafenib | To evaluate the correlation between DCE-MRI perfusion parameters (Ktrans, AUC, ve, kep, T1, Wash-in, Washout) at baseline, week 1 and week 2, and the response of target lesions to sorafenib. Ktrans: volume transfer constant between blood plasma and extravascular extracellular space AUC : area under the curve of tissue gadolinium concentration-time ve: fractional volume of extravascular extracellular space kep: rate constant between extravascular extracellular space and blood plasma (=Ktrans/ve) T1: longitudinal relaxation time Wash-in: slope of the early enhancement curve Washout: slope of the late enhancement curve The response of target lesions was assessed by mRECIST at 2 months after initiation of treatment (sorafenib). The correlation analyses were done using Pearson or Spearman correlation coefficient. | 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Correlation Coefficient Between DCE-MRI Perfusion Parameters at Baseline and Overall Survival | To evaluate the correlation between DCE-MRI perfusion parameters (Ktrans, AUC, ve, kep, T1, wash-in, washout) at baseline and overall survival. The overall survival was calculated from the patient's survival status recorded one year after initiation of the sorafenib treatment. The correlation analyses were done using Pearson or Spearman correlation coefficient. | 1 year | 
| Correlation Coefficient Between DCE-MRI Perfusion Parameters at Baseline and Progression Free Survival | To evaluate the correlation between DCE-MRI perfusion parameters (Ktrans, AUC, ve, kep, T1, wash-in, washout) at baseline and progression free survival. The progression free survival was calculated from the patient's survival status and tumor progression status recorded one year after initiation of the sorafenib treatment. The correlation analyses were done using Pearson or Spearman correlation coefficient. | 1 year | 
| Correlation Coefficient Between DCE-MRI Perfusion Parameters at Baseline and Time to Progression | To evaluate the correlation between DCE-MRI perfusion parameters (Ktrans, AUC, ve, kep, T1, wash-in, washout) at baseline and time to progression. The time to progression was calculated from the patient's survival status and tumor progression status recorded one year after initiation of the sorafenib treatment. The correlation analyses were done using Pearson or Spearman correlation coefficient. | 1 year | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
DCE-MRI, Sorafenib response