A Study of Ga-68 Dolacga to Evaluate Liver Reserve Function in Patients With HCC Before and After Proton Therapy

Study Overview
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Brief Summary
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This is a single-center, prospective, open-labeled, single-arm, interventional study to evaluate liver reserve and tumor response using Ga-68 Dolacga positron emission tomography and the safety of the investigational product in patients with hepatocellular carcinoma before and after proton therapy.

Detailed Description
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This is a single-center, prospective, open-labeled, single-arm, interventional study to evaluate liver reserve and tumor response using Ga-68 Dolacga positron emission tomography and the safety of the investigational product in patients with hepatocellular carcinoma before and after proton therapy. This trial will enroll 10 eligible subjects. All subjects will provide informed consent before any study procedures are performed. Screening procedures (visit 1) will occur within 21 days prior to imaging visit (visit 2) and will include: inclusion/exclusion criteria check, pregnancy test (if applicable), vital signs, laboratory tests, electrocardiogram (ECG) and establishment of baseline characteristics. Primovist MRI will occur within 14 days prior to imaging visit (visit 2) and 1 week after imaging visit (visit 4), and will be performed according to standard procedure of study site. The baseline characteristics include medical/medication history, fibrosis index, Child-Pugh score and classification, MELD score, liver oncology diagnosis, tumor size, preoperative treatments (portal vein embolization, transarterial chemoembolization, transarterial embolization or biliary drainage), existence of thrombosis (portal vein thrombosis or hepatic vein thrombosis). The liver tissue fibrosis index FIB-4 will be measured to assess the morphological changes. During the imaging session (visit 2, Day 1; visit 4, Day 84±3), a catheter will be placed for intravenous (IV) administration of Ga-68 Dolacga. Subjects will receive an iv bolus injection of 2.0±1.0 mCi Ga-68 Dolacga. A PET/CT scan will be kinetically performed for 60 minutes immediately after IV injection. The measurement of liver reserve is the primary endpoints of this study and measurement will be evaluated by Ga-68 Dolacga PET. The measurement of liver reserve will be performed at visit 2 and visit 4 of this study for all subjects. Adverse events will be continuously monitored during the imaging session. Two follow-up visits (visit 3 at Day 7±2 and visit 5 at Day 91±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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A Prospective Study of Ga-68 Dolacga Scintigraphy to Evaluate Liver Reserve Function in Patients With Hepatocellular Carcinoma Before and After Proton Therapy

Conditions
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Hepatic Carcinoma

Intervention / Treatment
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* Drug: Ga-68 Dolacga Injection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosed with hepatocellular carcinoma and scheduled to have the PBT. 20 80 years old Performance status: ECOG 0-1 Child-Pugh class A Exclusion Criteria: Massive or uncontrolled ascites Concurrent with other malignancy Under pregnancy or breastfeeding With distant metastasis Allergic to investigational drug(s) or similar drug(s)/ formulation(s); Known hypersensitivity to PRIMOVIST Acute or chronic severe renal insufficiency (glomerular filtration rate <30 mL/min/1.73m^2) General PET and MRI exclusion criteria Can't follow our follow-up schedule because of any reason

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 80 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: Ga-68 Dolacga Injection<br>Ga-68 Dolacga Injection, 2.0±1.0 mCi, single dose, iv bolus | Drug: Ga-68 Dolacga Injection<br>* Ga-68 Dolacga will be administered via iv bolus injection followed by a whole-body PET/CT scan for liver reserve evaluation.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Measurement of liver reserve obtained from the Ga-68 Dolacga PET performed in HCC patients before proton therapy. | The liver reserve parameters obtained from Ga-68 Dolacga PET is expressed in percentage of injection dose (%ID) and standard uptake value, (SUV). | Visit 2 (Day 1) | 
| Measurement of liver reserve obtained from the Ga-68 Dolacga PET performed in HCC patients after proton therapy. | The liver reserve parameters obtained from Ga-68 Dolacga PET is expressed in percentage of injection dose (%ID) and standard uptake value, (SUV). | Visit 4 (Day 84±3) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of subjects with clinically significant changes in systolic blood pressure and diastolic blood pressure |  | from pre-dose to visit 2 (Day 1), visit 3 (Day 7±2), visit 4 (84±3), and visit 5 (Day 91±2) | 
| Number of subjects with body temperature abnormalities |  | from pre-dose to visit 2 (Day 1), visit 3 (Day 7±2), visit 4 (84±3), and visit 5 (Day 91±2) | 
| Number of subjects with clinically significant changes in Heart Rate |  | from pre-dose to visit 2 (Day 1), visit 3 (Day 7±2), visit 4 (84±3), and visit 5 (Day 91±2) | 
| Number of subjects reporting clinically significant changes in serum biochemical tests |  | from pre-dose to visit 2 (Day 1), visit 3 (Day 7±2), visit 4 (84±3), and visit 5 (Day 91±2) | 
| Number of subjects reporting clinically significant changes in hematological tests |  | from pre-dose to visit 2 (Day 1), visit 3 (Day 7±2), visit 4 (84±3), and visit 5 (Day 91±2) | 
| Number of subjects reporting clinically significant changes in urinalysis |  | from pre-dose to visit 2 (Day 1), visit 3 (Day 7±2), visit 4 (84±3), and visit 5 (Day 91±2) | 
| Number of subjects with clinically significant changes in electrocardiogram(ECG) |  | from pre-dose to visit 2 (Day 1), visit 3 (Day 7±2), visit 4 (84±3), and visit 5 (Day 91±2) | 
| 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. | 91 days |