Trial Outcomes & Findings for DCE-MRI Using Dotarem® in Evaluation of Therapeutic Response to Sorafenib in Patients With Advanced Stage HCC (NCT NCT01806740)
NCT ID: NCT01806740
Last Updated: 2019-08-08
Results Overview
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.
Recruitment status
TERMINATED
Study phase
PHASE4
Target enrollment
37 participants
Primary outcome timeframe
3 months
Results posted on
2019-08-08
Participant Flow
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.
Participant milestones
| Measure |
Gadoterate Meglumine
All patients who received gadoterate meglumine.
|
|---|---|
|
Overall Study
STARTED
|
37
|
|
Overall Study
COMPLETED
|
31
|
|
Overall Study
NOT COMPLETED
|
6
|
Reasons for withdrawal
| Measure |
Gadoterate Meglumine
All patients who received gadoterate meglumine.
|
|---|---|
|
Overall Study
Withdrawal by Subject
|
4
|
|
Overall Study
Physician Decision
|
1
|
|
Overall Study
Patient's refusal of treatment
|
1
|
Baseline Characteristics
DCE-MRI Using Dotarem® in Evaluation of Therapeutic Response to Sorafenib in Patients With Advanced Stage HCC
Baseline characteristics by cohort
| Measure |
Gadoterate Meglumine
n=31 Participants
All patients who received gadoterate meglumine.
|
|---|---|
|
Age, Continuous
|
60.06 years
STANDARD_DEVIATION 10.78 • n=5 Participants
|
|
Sex: Female, Male
Female
|
4 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
27 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
31 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Weight
|
60.03 kg
STANDARD_DEVIATION 9.17 • n=5 Participants
|
PRIMARY outcome
Timeframe: 3 monthsPopulation: 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.
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.
Outcome measures
| Measure |
Baseline
n=25 Target lesions
DCE-MRI perfusion parameters assessed at baseline (initiation of the sorafenib treatment)
|
Week 1
n=25 Target lesions
DCE-MRI perfusion parameters assessed one week after initiation of the sorafenib treatment
|
Week 2
n=25 Target lesions
DCE-MRI perfusion parameters assessed two weeks after initiation of the sorafenib treatment
|
|---|---|---|---|
|
Correlation Coefficient Between DCE-MRI Perfusion Parameters and the Response of Target Lesions to Sorafenib
Wash-in (mean)
|
-0.42 correlation coefficient
|
-0.48 correlation coefficient
|
-0.52 correlation coefficient
|
|
Correlation Coefficient Between DCE-MRI Perfusion Parameters and the Response of Target Lesions to Sorafenib
Ktrans (mean)
|
-0.29 correlation coefficient
|
-0.38 correlation coefficient
|
-0.38 correlation coefficient
|
|
Correlation Coefficient Between DCE-MRI Perfusion Parameters and the Response of Target Lesions to Sorafenib
AUC (mean)
|
-0.53 correlation coefficient
|
-0.60 correlation coefficient
|
-0.62 correlation coefficient
|
|
Correlation Coefficient Between DCE-MRI Perfusion Parameters and the Response of Target Lesions to Sorafenib
ve (mean)
|
-0.19 correlation coefficient
|
-0.33 correlation coefficient
|
-0.34 correlation coefficient
|
|
Correlation Coefficient Between DCE-MRI Perfusion Parameters and the Response of Target Lesions to Sorafenib
kep (mean)
|
-0.07 correlation coefficient
|
-0.24 correlation coefficient
|
-0.17 correlation coefficient
|
|
Correlation Coefficient Between DCE-MRI Perfusion Parameters and the Response of Target Lesions to Sorafenib
T1 (mean)
|
0.05 correlation coefficient
|
0.30 correlation coefficient
|
0.18 correlation coefficient
|
|
Correlation Coefficient Between DCE-MRI Perfusion Parameters and the Response of Target Lesions to Sorafenib
Washout (mean)
|
-0.31 correlation coefficient
|
-0.48 correlation coefficient
|
-0.36 correlation coefficient
|
SECONDARY outcome
Timeframe: 1 yearPopulation: 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.
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.
Outcome measures
| Measure |
Baseline
n=23 Target lesions
DCE-MRI perfusion parameters assessed at baseline (initiation of the sorafenib treatment)
|
Week 1
DCE-MRI perfusion parameters assessed one week after initiation of the sorafenib treatment
|
Week 2
DCE-MRI perfusion parameters assessed two weeks after initiation of the sorafenib treatment
|
|---|---|---|---|
|
Correlation Coefficient Between DCE-MRI Perfusion Parameters at Baseline and Overall Survival
Ktrans (mean)
|
0.09 correlation coefficient
|
—
|
—
|
|
Correlation Coefficient Between DCE-MRI Perfusion Parameters at Baseline and Overall Survival
AUC (mean)
|
-0.08 correlation coefficient
|
—
|
—
|
|
Correlation Coefficient Between DCE-MRI Perfusion Parameters at Baseline and Overall Survival
ve (mean)
|
0.35 correlation coefficient
|
—
|
—
|
|
Correlation Coefficient Between DCE-MRI Perfusion Parameters at Baseline and Overall Survival
kep (mean)
|
-0.05 correlation coefficient
|
—
|
—
|
|
Correlation Coefficient Between DCE-MRI Perfusion Parameters at Baseline and Overall Survival
T1 (mean)
|
-0.14 correlation coefficient
|
—
|
—
|
|
Correlation Coefficient Between DCE-MRI Perfusion Parameters at Baseline and Overall Survival
Wash-in (mean)
|
-0.02 correlation coefficient
|
—
|
—
|
|
Correlation Coefficient Between DCE-MRI Perfusion Parameters at Baseline and Overall Survival
Washout (mean)
|
-0.04 correlation coefficient
|
—
|
—
|
SECONDARY outcome
Timeframe: 1 yearPopulation: 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.
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.
Outcome measures
| Measure |
Baseline
n=22 Target lesions
DCE-MRI perfusion parameters assessed at baseline (initiation of the sorafenib treatment)
|
Week 1
DCE-MRI perfusion parameters assessed one week after initiation of the sorafenib treatment
|
Week 2
DCE-MRI perfusion parameters assessed two weeks after initiation of the sorafenib treatment
|
|---|---|---|---|
|
Correlation Coefficient Between DCE-MRI Perfusion Parameters at Baseline and Progression Free Survival
Ktrans (mean)
|
-0.24 correlation coefficient
|
—
|
—
|
|
Correlation Coefficient Between DCE-MRI Perfusion Parameters at Baseline and Progression Free Survival
AUC (mean)
|
-0.45 correlation coefficient
|
—
|
—
|
|
Correlation Coefficient Between DCE-MRI Perfusion Parameters at Baseline and Progression Free Survival
ve (mean)
|
0.17 correlation coefficient
|
—
|
—
|
|
Correlation Coefficient Between DCE-MRI Perfusion Parameters at Baseline and Progression Free Survival
kep (mean)
|
-0.23 correlation coefficient
|
—
|
—
|
|
Correlation Coefficient Between DCE-MRI Perfusion Parameters at Baseline and Progression Free Survival
T1 (mean)
|
-0.15 correlation coefficient
|
—
|
—
|
|
Correlation Coefficient Between DCE-MRI Perfusion Parameters at Baseline and Progression Free Survival
Wash-in (mean)
|
-0.31 correlation coefficient
|
—
|
—
|
|
Correlation Coefficient Between DCE-MRI Perfusion Parameters at Baseline and Progression Free Survival
Washout (mean)
|
-0.29 correlation coefficient
|
—
|
—
|
SECONDARY outcome
Timeframe: 1 yearPopulation: Among the 15 patients of the full analysis set (26 target lesions), 4 patients had data for time to progression (7 target lesions).
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.
Outcome measures
| Measure |
Baseline
n=7 Target lesions
DCE-MRI perfusion parameters assessed at baseline (initiation of the sorafenib treatment)
|
Week 1
DCE-MRI perfusion parameters assessed one week after initiation of the sorafenib treatment
|
Week 2
DCE-MRI perfusion parameters assessed two weeks after initiation of the sorafenib treatment
|
|---|---|---|---|
|
Correlation Coefficient Between DCE-MRI Perfusion Parameters at Baseline and Time to Progression
T1 (mean)
|
0.24 correlation coefficient
|
—
|
—
|
|
Correlation Coefficient Between DCE-MRI Perfusion Parameters at Baseline and Time to Progression
Ktrans (mean)
|
-0.72 correlation coefficient
|
—
|
—
|
|
Correlation Coefficient Between DCE-MRI Perfusion Parameters at Baseline and Time to Progression
AUC (mean)
|
-0.64 correlation coefficient
|
—
|
—
|
|
Correlation Coefficient Between DCE-MRI Perfusion Parameters at Baseline and Time to Progression
ve (mean)
|
-0.68 correlation coefficient
|
—
|
—
|
|
Correlation Coefficient Between DCE-MRI Perfusion Parameters at Baseline and Time to Progression
kep (mean)
|
-0.17 correlation coefficient
|
—
|
—
|
|
Correlation Coefficient Between DCE-MRI Perfusion Parameters at Baseline and Time to Progression
Wash-in (mean)
|
-0.70 correlation coefficient
|
—
|
—
|
|
Correlation Coefficient Between DCE-MRI Perfusion Parameters at Baseline and Time to Progression
Washout (mean)
|
-0.42 correlation coefficient
|
—
|
—
|
Adverse Events
Gadoterate Meglumine
Serious events: 7 serious events
Other events: 29 other events
Deaths: 1 deaths
Serious adverse events
| Measure |
Gadoterate Meglumine
n=31 participants at risk
All patients who received gadoterate meglumine.
|
|---|---|
|
Gastrointestinal disorders
Abdominal pain upper
|
3.2%
1/31 • Number of events 1 • 3 months (from the informed consent signature to 2 months after initiation of the sorafenib treatment)
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumor necrosis
|
3.2%
1/31 • Number of events 1 • 3 months (from the informed consent signature to 2 months after initiation of the sorafenib treatment)
|
|
Gastrointestinal disorders
Gastric varices haemorrhage
|
3.2%
1/31 • Number of events 1 • 3 months (from the informed consent signature to 2 months after initiation of the sorafenib treatment)
|
|
Gastrointestinal disorders
Oesophageal varices haemorrhage
|
3.2%
1/31 • Number of events 1 • 3 months (from the informed consent signature to 2 months after initiation of the sorafenib treatment)
|
|
Infections and infestations
Upper respiratory tract infection
|
3.2%
1/31 • Number of events 1 • 3 months (from the informed consent signature to 2 months after initiation of the sorafenib treatment)
|
|
Nervous system disorders
Hepatic encephalopathy
|
3.2%
1/31 • Number of events 1 • 3 months (from the informed consent signature to 2 months after initiation of the sorafenib treatment)
|
|
Hepatobiliary disorders
Cholecystitis acute
|
3.2%
1/31 • Number of events 1 • 3 months (from the informed consent signature to 2 months after initiation of the sorafenib treatment)
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Malignant neoplasm progression
|
6.5%
2/31 • Number of events 2 • 3 months (from the informed consent signature to 2 months after initiation of the sorafenib treatment)
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory failure
|
3.2%
1/31 • Number of events 1 • 3 months (from the informed consent signature to 2 months after initiation of the sorafenib treatment)
|
Other adverse events
| Measure |
Gadoterate Meglumine
n=31 participants at risk
All patients who received gadoterate meglumine.
|
|---|---|
|
Gastrointestinal disorders
Diarrhoea
|
32.3%
10/31 • Number of events 11 • 3 months (from the informed consent signature to 2 months after initiation of the sorafenib treatment)
|
|
Gastrointestinal disorders
Nausea
|
19.4%
6/31 • Number of events 6 • 3 months (from the informed consent signature to 2 months after initiation of the sorafenib treatment)
|
|
Gastrointestinal disorders
Abdominal pain
|
16.1%
5/31 • Number of events 5 • 3 months (from the informed consent signature to 2 months after initiation of the sorafenib treatment)
|
|
Gastrointestinal disorders
Abdominal pain upper
|
9.7%
3/31 • Number of events 4 • 3 months (from the informed consent signature to 2 months after initiation of the sorafenib treatment)
|
|
Gastrointestinal disorders
Ascites
|
6.5%
2/31 • Number of events 2 • 3 months (from the informed consent signature to 2 months after initiation of the sorafenib treatment)
|
|
Gastrointestinal disorders
Constipation
|
6.5%
2/31 • Number of events 2 • 3 months (from the informed consent signature to 2 months after initiation of the sorafenib treatment)
|
|
Gastrointestinal disorders
Abdominal distension
|
3.2%
1/31 • Number of events 1 • 3 months (from the informed consent signature to 2 months after initiation of the sorafenib treatment)
|
|
Gastrointestinal disorders
Chronic gastritis
|
3.2%
1/31 • Number of events 1 • 3 months (from the informed consent signature to 2 months after initiation of the sorafenib treatment)
|
|
Gastrointestinal disorders
Dyspepsia
|
3.2%
1/31 • Number of events 1 • 3 months (from the informed consent signature to 2 months after initiation of the sorafenib treatment)
|
|
Gastrointestinal disorders
Portal hypertensive gastropathy
|
3.2%
1/31 • Number of events 1 • 3 months (from the informed consent signature to 2 months after initiation of the sorafenib treatment)
|
|
Gastrointestinal disorders
Stomatitis
|
3.2%
1/31 • Number of events 1 • 3 months (from the informed consent signature to 2 months after initiation of the sorafenib treatment)
|
|
Gastrointestinal disorders
Vomiting
|
3.2%
1/31 • Number of events 1 • 3 months (from the informed consent signature to 2 months after initiation of the sorafenib treatment)
|
|
Skin and subcutaneous tissue disorders
Palmar-plantar erythrodysaesthesia syndrome
|
48.4%
15/31 • Number of events 15 • 3 months (from the informed consent signature to 2 months after initiation of the sorafenib treatment)
|
|
Skin and subcutaneous tissue disorders
Rash
|
12.9%
4/31 • Number of events 4 • 3 months (from the informed consent signature to 2 months after initiation of the sorafenib treatment)
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
9.7%
3/31 • Number of events 3 • 3 months (from the informed consent signature to 2 months after initiation of the sorafenib treatment)
|
|
Skin and subcutaneous tissue disorders
Cold sweat
|
3.2%
1/31 • Number of events 1 • 3 months (from the informed consent signature to 2 months after initiation of the sorafenib treatment)
|
|
Skin and subcutaneous tissue disorders
Pain of skin
|
3.2%
1/31 • Number of events 1 • 3 months (from the informed consent signature to 2 months after initiation of the sorafenib treatment)
|
|
Skin and subcutaneous tissue disorders
Palmoplantar keratoderma
|
3.2%
1/31 • Number of events 1 • 3 months (from the informed consent signature to 2 months after initiation of the sorafenib treatment)
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
3.2%
1/31 • Number of events 1 • 3 months (from the informed consent signature to 2 months after initiation of the sorafenib treatment)
|
|
Skin and subcutaneous tissue disorders
Urticaria
|
3.2%
1/31 • Number of events 1 • 3 months (from the informed consent signature to 2 months after initiation of the sorafenib treatment)
|
|
Investigations
Blood pressure increased
|
9.7%
3/31 • Number of events 3 • 3 months (from the informed consent signature to 2 months after initiation of the sorafenib treatment)
|
|
Investigations
Weight decreased
|
6.5%
2/31 • Number of events 2 • 3 months (from the informed consent signature to 2 months after initiation of the sorafenib treatment)
|
|
Investigations
Alanine aminotransferase increased
|
3.2%
1/31 • Number of events 1 • 3 months (from the informed consent signature to 2 months after initiation of the sorafenib treatment)
|
|
Investigations
Aspartate aminotransferase increased
|
3.2%
1/31 • Number of events 1 • 3 months (from the informed consent signature to 2 months after initiation of the sorafenib treatment)
|
|
Investigations
Blood bilirubin increased
|
3.2%
1/31 • Number of events 1 • 3 months (from the informed consent signature to 2 months after initiation of the sorafenib treatment)
|
|
Investigations
Blood potassium decreased
|
3.2%
1/31 • Number of events 1 • 3 months (from the informed consent signature to 2 months after initiation of the sorafenib treatment)
|
|
Nervous system disorders
Headache
|
9.7%
3/31 • Number of events 3 • 3 months (from the informed consent signature to 2 months after initiation of the sorafenib treatment)
|
|
Nervous system disorders
Dizziness
|
6.5%
2/31 • Number of events 3 • 3 months (from the informed consent signature to 2 months after initiation of the sorafenib treatment)
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
6.5%
2/31 • Number of events 2 • 3 months (from the informed consent signature to 2 months after initiation of the sorafenib treatment)
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
3.2%
1/31 • Number of events 1 • 3 months (from the informed consent signature to 2 months after initiation of the sorafenib treatment)
|
|
Respiratory, thoracic and mediastinal disorders
Dysphonia
|
3.2%
1/31 • Number of events 1 • 3 months (from the informed consent signature to 2 months after initiation of the sorafenib treatment)
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea exertional
|
3.2%
1/31 • Number of events 1 • 3 months (from the informed consent signature to 2 months after initiation of the sorafenib treatment)
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
6.5%
2/31 • Number of events 3 • 3 months (from the informed consent signature to 2 months after initiation of the sorafenib treatment)
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
3.2%
1/31 • Number of events 1 • 3 months (from the informed consent signature to 2 months after initiation of the sorafenib treatment)
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
3.2%
1/31 • Number of events 1 • 3 months (from the informed consent signature to 2 months after initiation of the sorafenib treatment)
|
|
General disorders
Pyrexia
|
6.5%
2/31 • Number of events 2 • 3 months (from the informed consent signature to 2 months after initiation of the sorafenib treatment)
|
|
General disorders
Asthenia
|
3.2%
1/31 • Number of events 1 • 3 months (from the informed consent signature to 2 months after initiation of the sorafenib treatment)
|
|
General disorders
Peripheral swelling
|
3.2%
1/31 • Number of events 1 • 3 months (from the informed consent signature to 2 months after initiation of the sorafenib treatment)
|
|
Metabolism and nutrition disorders
Decreased appetite
|
9.7%
3/31 • Number of events 3 • 3 months (from the informed consent signature to 2 months after initiation of the sorafenib treatment)
|
|
Reproductive system and breast disorders
Penile erythema
|
3.2%
1/31 • Number of events 1 • 3 months (from the informed consent signature to 2 months after initiation of the sorafenib treatment)
|
|
Reproductive system and breast disorders
Penile oedema
|
3.2%
1/31 • Number of events 1 • 3 months (from the informed consent signature to 2 months after initiation of the sorafenib treatment)
|
|
Blood and lymphatic system disorders
Anaemia
|
3.2%
1/31 • Number of events 1 • 3 months (from the informed consent signature to 2 months after initiation of the sorafenib treatment)
|
|
Cardiac disorders
Arrhythmia
|
3.2%
1/31 • Number of events 1 • 3 months (from the informed consent signature to 2 months after initiation of the sorafenib treatment)
|
|
Renal and urinary disorders
Nocturia
|
3.2%
1/31 • Number of events 1 • 3 months (from the informed consent signature to 2 months after initiation of the sorafenib treatment)
|
|
Infections and infestations
Upper respiratory tract infection
|
3.2%
1/31 • Number of events 1 • 3 months (from the informed consent signature to 2 months after initiation of the sorafenib treatment)
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: OTHER