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

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

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.

Study Overview

• Status: Terminated
• Conditions: Hepatocellular Carcinoma
• Intervention / Treatment: Drug: Gadoterate meglumine

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.

• Study Type: Interventional
• Enrollment (Actual): 37
• Phase: Phase 4

Contacts and Locations

Study Locations

• Korea, Republic of
  • Gangnam Gu
    • Seoul, Gangnam Gu, Korea, Republic of, 135-920
      • Guerbet Korea

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

1. Male and female adult patients (age ≥ 20 years old)
2. Patients diagnosed with unresectable HCC [Child Pugh class A and major vascular invasion, extrahapatic metastasis, or progression after transarterial chemoembolization more than 2 times]
3. 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]
4. Patients planned to be treated with sorafenib
5. Patient with liver CT performed or planned to be performed within 4 weeks before initiation of sorafenib treatment
6. Patient with a life expectancy of 12 weeks or more
7. No previous treatment with sorafenib
8. 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: DIAGNOSTIC
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Gadoterate meglumine; there is one single arm of patients (no comparative arm)	Drug: Gadoterate meglumine; 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.; Other Names: Dotarem; gadoteric acid

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

Collaborators and Investigators

• Sponsor: Guerbet
• Investigators: Principal Investigator: Jeong Min Lee, Ph.D, Seoul National University Hospital

Study record dates

Study Major Dates

• Study Start (ACTUAL): May 9, 2013
• Primary Completion (ACTUAL): October 12, 2015
• Study Completion (ACTUAL): October 12, 2015

Study Registration Dates

• First Submitted: November 6, 2012
• First Submitted That Met QC Criteria: March 6, 2013
• First Posted (ESTIMATE): March 7, 2013

Study Record Updates

• Last Update Posted (ACTUAL): August 8, 2019
• Last Update Submitted That Met QC Criteria: June 24, 2019
• Last Verified: June 1, 2019

More Information

Terms related to this study

• Keywords: DCE-MRI; Sorafenib response
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Digestive System Neoplasms; Liver Diseases; Liver Neoplasms; Carcinoma, Hepatocellular; Molecular Mechanisms of Pharmacological Action; Chelating Agents; Sequestering Agents; Gadolinium 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetate
• Other Study ID Numbers: DGD-44-057

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: It will be decided after study completion.