to Assess the Accuracy and Reliability of the Ga68-Dolacga Positron Emission Tomography Compared to Computer Tomography Volumetry and Indocyanine Green Retention Test for Measurement of Liver Reserve

Study Overview
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Brief Summary
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This is a phase 2 open-labeled study to compare the Ga68-Dolacga positron emission tomography with computer tomography volumetry and indocyanine green retention test for measurement of liver reserve among scheduled surgery operation patients.

Detailed Description
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This is a phase 2 open-labeled study to compare the Ga68-Dolacga positron emission tomography with computer tomography volumetry (CTV) and indocyanine green retention test (ICGR15) for measurement of liver reserve among scheduled surgery operation patients. The goal is to enroll 30 eligible subjects scheduled for surgery operation. CTV and ICGR15 will occur within 7 days prior to the imaging visit for all eligible subjects. During the imaging visit (visit 2, Day 1), subjects will receive an iv bolus injection of 2.0±1.0 mCi Ga68-Dolacga Injection. Ga68-Dolacga PET will be kinetically performed 60 minutes immediately after iv injection. Two follow-up visits (visit 3 at Day 7±2 and visit 4 at Day 14±2) will be conducted to confirm subject well-being and to collect information about any new adverse events (if any).

Official Title
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An Open-label, Comparative Phase II Clinical Trial to Assess the Accuracy and Reliability of the Ga68-Dolacga Positron Emission Tomography Compared to Computer Tomography Volumetry and Indocyanine Green Retention Test for Measurement of Liver Reserve Among Scheduled Surgery Operation Patients

Conditions
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Hepatic Carcinoma

Intervention / Treatment
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* Drug: Ga68-Dolacga Injection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Scheduled operation subjects with diagnosed hepatic carcinoma. The eligibility criteria for operation refer to protocol Appendix II: Diagnosis and Treatment Guidelines for Hepatocellular Carcinoma in Chang Gung Memorial Hospital; Subjects without ascites or with controllable ascites; Serum total bilirubin level < 2.0 mg/dL; Written informed consent must be obtained before any assessment is performed. Male or female subjects aged 20 or above, inclusive, at date of consent. Exclusion Criteria: Presence of distant metastases; A body weight loss of >10% during the 6 months before operation; Presence of seriously impaired function of vital organs due to respiratory, renal, or heart disease; Cholangiocarcinoma; General PET exclusion criteria; Pregnant women, lactating or breast-feeding women; Patient who can't be followed up for any reason.

Ages Eligible for Study
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Minimum Age: 20 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ga68-Dolacga Injection<br>Ga68-Dolacga will be administered via iv bolus injection followed by a whole-body PET/CT scan for liver reserve evaluation. | Drug: Ga68-Dolacga Injection<br>* Ga68-Dolacga Injection, 2.0±1.0 mCi, single dose, iv bolus<br>* Other names: Ga68-INER038;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Measurement of liver reserve obtained from Ga68-Dolacga PET performed in patients scheduled surgical operation (Percentage of injection dose, %ID) | The liver reserve obtained from Ga68-Dolacga PET is expressed in percentage of injection dose (%ID). | visit 2 (Day 1) | 
| Measurement of liver reserve obtained from CTV performed in patients scheduled surgical operation (Remnant volume rate (%)) | The liver reserve obtained from computer tomography volumetry (CTV) is expressed in remnant volume rate (%). | within 7 days prior to Day 1 | 
| Measurement of future liver remnant volume rate (FLRV%) | The future liver remnant volume rate (FLRV%) is calculated by dividing the future remnant liver volume by the total functional liver volume from CTV and expressed as %. | within 7 days prior to Day 1 | 
| Measurement of future liver remnant function rate (FLRF%) | The future liver remnant function rate (FLRV%) is calculated by dividing the uptake in the future remnant liver volume by the uptake in the total liver volume from Ga68-Dolacga PET and expressed as %. | visit 2 (Day 1) | 
| Correlation of the percentage of injection dose (%ID) in liver determined by Ga68-Dolacga PET with conventional liver function tests | The conventional liver function tests parameters include alanine aminotransferase (U/L), aspartate aminotransferase (U/L), total bilirubin (mg/dL), direct bilirubin (mg/dL), gamma-glutamyl transpeptidase (U/L), total protein (g/dL), albumin/globulin ratio, albumin (g/dL), prothrombin time/International Normalized Ratio (PT/INR), platelet count (×10^3/μL), ICGR15 (%), Child-Pugh classification (Class A to Class C), MELD score. | from pre-dose to Day 1 | 
| Correlation of the remnant volume rate determined by CTV with conventional liver function tests | The conventional liver function tests parameters include alanine aminotransferase (U/L), aspartate aminotransferase (U/L), total bilirubin (mg/dL), direct bilirubin (mg/dL), gamma-glutamyl transpeptidase (U/L), total protein (g/dL), albumin/globulin ratio, albumin (g/dL), prothrombin time/International Normalized Ratio (PT/INR), platelet count (×10^3/μL), ICGR15 (%), Child-Pugh classification (Class A to Class C), MELD score. | from pre-dose to Day 1 | 
| Correlation of the ICGR15 with the conventional liver function tests | The conventional liver function tests parameters include alanine aminotransferase (U/L), aspartate aminotransferase (U/L), total bilirubin (mg/dL), direct bilirubin (mg/dL), gamma-glutamyl transpeptidase (U/L), total protein (g/dL), albumin/globulin ratio, albumin (g/dL), prothrombin time/International Normalized Ratio (PT/INR), platelet count (×10^3/μL), Child-Pugh classification (Class A to Class C), MELD score. | from pre-dose to Day 1 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Correlation of the percentage of injection dose (%ID) in liver determined by Ga68-Dolacga PET with the fibrosis indices | The fibrosis indices include liver stiffness measurement (kPa) determined by Fibroscan and the Fibrosis-4 (FIB-4) index. | from pre-dose to Day 1 | 
| Correlation of the ICGR15 with the fibrosis indices | The fibrosis indices include liver stiffness measurement (kPa) determined by Fibroscan and the Fibrosis-4 (FIB-4) index. | from pre-dose to Day 1 | 
| Number of subjects with clinically significant changes in systolic blood pressure and diastolic blood pressure |  | from pre-dose to 14±2 days post dose | 
| Number of subjects with body temperature abnormalities |  | from pre-dose to 14±2 days post dose | 
| Number of subjects with clinically significant changes in Heart Rate |  | from pre-dose to 14±2 days post dose | 
| Number of subjects reporting clinically significant changes in serum biochemical tests |  | from pre-dose to 14±2 days post dose | 
| Number of subjects reporting clinically significant changes in hematological tests |  | from pre-dose to 14±2 days post dose | 
| Number of subjects reporting clinically significant changes in urinalysis |  | from pre-dose to 14±2 days post dose | 
| Number of subjects with clinically significant changes in electrocardiogram(ECG) | The ECG parameters include: PR interval (milliseconds), QTc interval (milliseconds), QRS duration (milliseconds) | from pre-dose to 14±2 days post dose | 
| Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs) | All laboratory abnormalities which are compared with screening values and out of the reference range will be considered as AE and will be assessed its relationship to the study drug. Any ECG changes including ECG waveform will be assessed as AE(s) and will be followed to assess whether they resolved and when they resolved. | 14 days | 
| Incidence of posthepatectomy liver failure (PHLF) |  | on or after postoperative day 5 (POD 5) | 
| Severity grading of PHLF as defined by the International Study Group of Liver Surgery (ISGLS) | Subjects diagnosed with PHLF are classified as grade A, grade B or grade C based on its severity. | on or after postoperative day 5 (POD 5) | 
| Comparison of CTV and Ga68-Dolacga PET parameters in patients with PHLF | Following parameters will be compared: liver reserve obtained from CTV vs liver reserve obtained from Ga68-Dolacga PET FLRV% vs FLRF% | on or after postoperative day 5 (POD 5) |