Hepatocellular Carcinoma
Conditions
Keywords
DCE-MRI, Sorafenib response
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.
Interventions
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.
Sponsors
Guerbet
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
Healthy volunteers
No
Inclusion criteria
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Correlation Coefficient Between DCE-MRI Perfusion Parameters and the Response of Target Lesions to Sorafenib | 3 months | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Correlation Coefficient Between DCE-MRI Perfusion Parameters at Baseline and Overall Survival | 1 year | 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. |
| Correlation Coefficient Between DCE-MRI Perfusion Parameters at Baseline and Progression Free Survival | 1 year | 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. |
| Correlation Coefficient Between DCE-MRI Perfusion Parameters at Baseline and Time to Progression | 1 year | 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. |
Countries
South Korea
Participant flow
Recruitment details
Despite several extensions of the recruitment period, the planned number of enrolled patients was still not reached after 2 years and the study was prematurely discontinued. A total of 37 patients were enrolled in four study sites.
Participants by arm
| Arm | Count |
|---|---|
| Gadoterate Meglumine All patients who received gadoterate meglumine. | 31 |
| Total | 31 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Patient's refusal of treatment | 1 |
| Overall Study | Physician Decision | 1 |
| Overall Study | Withdrawal by Subject | 4 |
Baseline characteristics
| Characteristic | Gadoterate Meglumine |
|---|---|
| Age, Continuous | 60.06 years STANDARD_DEVIATION 10.78 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 31 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 0 Participants |
| Sex: Female, Male Female | 4 Participants |
| Sex: Female, Male Male | 27 Participants |
| Weight | 60.03 kg STANDARD_DEVIATION 9.17 |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 1 / 31 |
| other Total, other adverse events | 29 / 31 |
| serious Total, serious adverse events | 7 / 31 |
Outcome results
Primary
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.
Time frame: 3 months
Population: A total of 26 target lesions were identified in the 15 patients of the full analysis set (patients with available data for the primary criteria). One lesion was not assessed at baseline, week 1 and week 2 for all parameters and one lesion was not assessed at baseline and week 1 for Ktrans, ve and kep.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Baseline | Correlation Coefficient Between DCE-MRI Perfusion Parameters and the Response of Target Lesions to Sorafenib | ve (mean) | -0.19 correlation coefficient |
| Baseline | Correlation Coefficient Between DCE-MRI Perfusion Parameters and the Response of Target Lesions to Sorafenib | Washout (mean) | -0.31 correlation coefficient |
| Baseline | Correlation Coefficient Between DCE-MRI Perfusion Parameters and the Response of Target Lesions to Sorafenib | AUC (mean) | -0.53 correlation coefficient |
| Baseline | Correlation Coefficient Between DCE-MRI Perfusion Parameters and the Response of Target Lesions to Sorafenib | Wash-in (mean) | -0.42 correlation coefficient |
| Baseline | Correlation Coefficient Between DCE-MRI Perfusion Parameters and the Response of Target Lesions to Sorafenib | Ktrans (mean) | -0.29 correlation coefficient |
| Baseline | Correlation Coefficient Between DCE-MRI Perfusion Parameters and the Response of Target Lesions to Sorafenib | kep (mean) | -0.07 correlation coefficient |
| Baseline | Correlation Coefficient Between DCE-MRI Perfusion Parameters and the Response of Target Lesions to Sorafenib | T1 (mean) | 0.05 correlation coefficient |
| Week 1 | Correlation Coefficient Between DCE-MRI Perfusion Parameters and the Response of Target Lesions to Sorafenib | ve (mean) | -0.33 correlation coefficient |
| Week 1 | Correlation Coefficient Between DCE-MRI Perfusion Parameters and the Response of Target Lesions to Sorafenib | Wash-in (mean) | -0.48 correlation coefficient |
| Week 1 | Correlation Coefficient Between DCE-MRI Perfusion Parameters and the Response of Target Lesions to Sorafenib | Washout (mean) | -0.48 correlation coefficient |
| Week 1 | Correlation Coefficient Between DCE-MRI Perfusion Parameters and the Response of Target Lesions to Sorafenib | T1 (mean) | 0.30 correlation coefficient |
| Week 1 | Correlation Coefficient Between DCE-MRI Perfusion Parameters and the Response of Target Lesions to Sorafenib | kep (mean) | -0.24 correlation coefficient |
| Week 1 | Correlation Coefficient Between DCE-MRI Perfusion Parameters and the Response of Target Lesions to Sorafenib | AUC (mean) | -0.60 correlation coefficient |
| Week 1 | Correlation Coefficient Between DCE-MRI Perfusion Parameters and the Response of Target Lesions to Sorafenib | Ktrans (mean) | -0.38 correlation coefficient |
| Week 2 | Correlation Coefficient Between DCE-MRI Perfusion Parameters and the Response of Target Lesions to Sorafenib | Washout (mean) | -0.36 correlation coefficient |
| Week 2 | Correlation Coefficient Between DCE-MRI Perfusion Parameters and the Response of Target Lesions to Sorafenib | Ktrans (mean) | -0.38 correlation coefficient |
| Week 2 | Correlation Coefficient Between DCE-MRI Perfusion Parameters and the Response of Target Lesions to Sorafenib | AUC (mean) | -0.62 correlation coefficient |
| Week 2 | Correlation Coefficient Between DCE-MRI Perfusion Parameters and the Response of Target Lesions to Sorafenib | kep (mean) | -0.17 correlation coefficient |
| Week 2 | Correlation Coefficient Between DCE-MRI Perfusion Parameters and the Response of Target Lesions to Sorafenib | T1 (mean) | 0.18 correlation coefficient |
| Week 2 | Correlation Coefficient Between DCE-MRI Perfusion Parameters and the Response of Target Lesions to Sorafenib | ve (mean) | -0.34 correlation coefficient |
| Week 2 | Correlation Coefficient Between DCE-MRI Perfusion Parameters and the Response of Target Lesions to Sorafenib | Wash-in (mean) | -0.52 correlation coefficient |
Secondary
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.
Time frame: 1 year
Population: Among the 15 patients of the full analysis set (26 target lesions), one patient was lost to follow-up. Consequently, 14 patients had data for overall survival (23 target lesions). One lesion was not assessed for Ktrans, ve and kep.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Baseline | Correlation Coefficient Between DCE-MRI Perfusion Parameters at Baseline and Overall Survival | kep (mean) | -0.05 correlation coefficient |
| Baseline | Correlation Coefficient Between DCE-MRI Perfusion Parameters at Baseline and Overall Survival | T1 (mean) | -0.14 correlation coefficient |
| Baseline | Correlation Coefficient Between DCE-MRI Perfusion Parameters at Baseline and Overall Survival | Wash-in (mean) | -0.02 correlation coefficient |
| Baseline | Correlation Coefficient Between DCE-MRI Perfusion Parameters at Baseline and Overall Survival | Washout (mean) | -0.04 correlation coefficient |
| Baseline | Correlation Coefficient Between DCE-MRI Perfusion Parameters at Baseline and Overall Survival | Ktrans (mean) | 0.09 correlation coefficient |
| Baseline | Correlation Coefficient Between DCE-MRI Perfusion Parameters at Baseline and Overall Survival | AUC (mean) | -0.08 correlation coefficient |
| Baseline | Correlation Coefficient Between DCE-MRI Perfusion Parameters at Baseline and Overall Survival | ve (mean) | 0.35 correlation coefficient |
Secondary
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.
Time frame: 1 year
Population: Among the 15 patients of the full analysis set (26 target lesions), 13 had data for progression free survival (22 target lesions). One lesion was not assessed for Ktrans, ve and kep.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Baseline | Correlation Coefficient Between DCE-MRI Perfusion Parameters at Baseline and Progression Free Survival | Ktrans (mean) | -0.24 correlation coefficient |
| Baseline | Correlation Coefficient Between DCE-MRI Perfusion Parameters at Baseline and Progression Free Survival | AUC (mean) | -0.45 correlation coefficient |
| Baseline | Correlation Coefficient Between DCE-MRI Perfusion Parameters at Baseline and Progression Free Survival | ve (mean) | 0.17 correlation coefficient |
| Baseline | Correlation Coefficient Between DCE-MRI Perfusion Parameters at Baseline and Progression Free Survival | kep (mean) | -0.23 correlation coefficient |
| Baseline | Correlation Coefficient Between DCE-MRI Perfusion Parameters at Baseline and Progression Free Survival | T1 (mean) | -0.15 correlation coefficient |
| Baseline | Correlation Coefficient Between DCE-MRI Perfusion Parameters at Baseline and Progression Free Survival | Wash-in (mean) | -0.31 correlation coefficient |
| Baseline | Correlation Coefficient Between DCE-MRI Perfusion Parameters at Baseline and Progression Free Survival | Washout (mean) | -0.29 correlation coefficient |
Secondary
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.
Time frame: 1 year
Population: Among the 15 patients of the full analysis set (26 target lesions), 4 patients had data for time to progression (7 target lesions).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Baseline | Correlation Coefficient Between DCE-MRI Perfusion Parameters at Baseline and Time to Progression | Wash-in (mean) | -0.70 correlation coefficient |
| Baseline | Correlation Coefficient Between DCE-MRI Perfusion Parameters at Baseline and Time to Progression | Washout (mean) | -0.42 correlation coefficient |
| Baseline | Correlation Coefficient Between DCE-MRI Perfusion Parameters at Baseline and Time to Progression | Ktrans (mean) | -0.72 correlation coefficient |
| Baseline | Correlation Coefficient Between DCE-MRI Perfusion Parameters at Baseline and Time to Progression | AUC (mean) | -0.64 correlation coefficient |
| Baseline | Correlation Coefficient Between DCE-MRI Perfusion Parameters at Baseline and Time to Progression | ve (mean) | -0.68 correlation coefficient |
| Baseline | Correlation Coefficient Between DCE-MRI Perfusion Parameters at Baseline and Time to Progression | kep (mean) | -0.17 correlation coefficient |
| Baseline | Correlation Coefficient Between DCE-MRI Perfusion Parameters at Baseline and Time to Progression | T1 (mean) | 0.24 correlation coefficient |