Overview

The phase I/II, double-blind, randomized study will investigate the efficacy and safety of TACE/TAE treatment with T-ACE Oil in patients with unresectable hepatocellular carcinoma.

Eligibility

Inclusion Criteria:

1. Age of over 20 years (or according to local legal definition of majority).
2. Patients diagnosed of HCC (Meet at least ONE of the following criteria):
   • 2-1. Diagnosed via tumor biopsy by pathologists and confirmed by on-service physician.
   • 2-2. High risk patients (viral hepatitis B or C or cirrhotic) with typical liver cancer image appeared on MRI or CT scan.
3. In very early stage to intermediate stage by BCLC staging (2018 AASLD), HCC tumor

   numbers ≦ 10, HCC tumor size ≦ 15 centimeters (determined by CT, MRI or ultrasound), with liver function at Child-Pugh score[1] ≦ 8.

4. Disease can be treated by trans-arterial chemoembolization, and can be evaluated by Magnetic resonance imaging (MRI), or computed tomography(CT).
5. Patients who only require a single TAE/TACE treatment to treat all HCC tumors at once.
6. Target HCC tumors should have at least 1 tumor that is larger than 1 cm in diameter (determined by CT, MRI or ultrasound) and non-treated before.
7. May have received local therapy such as TAE, TACE, radiofrequency ablation(RFA) or surgery and remain eligible for study provided the prior therapy was within the following timeframes and the subject has fully recovered from prior therapy:
   • 7-1. TAE/TACE: more than 8 weeks since completion of prior therapy
   • 7-2. RFA: After PI confirm subject is fully recovered from prior therapy based on screening visit physical examination and liver function laboratory tests results.
   • 7-3. Surgery: After PI confirm subject is fully recovered from prior therapy based on screening visit physical examination and liver function laboratory tests results.
8. Patients able to understand, willing to accept and cooperate with all clinical trial

   practices.

9. Willing to sign a written informed consent form

Exclusion Criteria:

1. Major branch of portal vein has been invaded by HCC, extrahepatic metastasis or other malignant tumors (current active malignancy or active malignancy within the past 5 years).
2. Eligible for curative surgery or transplant as judged by PI.
3. Evidences of decompensation (Meet at least ONE of the following criteria):
   • 3-1. Total Bilirubin > 2 mg/dL
   • 3-2. INR > 1.7
   • 3-3. Child-Pugh score > 9
   • 3-4. refractory ascites
   • 3-5. active bleeding
   • 3-6. hepatic encephalopathy
   • 3-7. severe infection
4. Any of the following findings (but not limit to):
   • 4-1. Heart failure (NYHA Class III or IV), COPD (Stage III or IV)
   • 4-2. A marked baseline prolongation of QT/QTc interval (e.g., repeated demonstration of a QTc interval >480 milliseconds (ms) (CTCAE grade 1) using Fridericia's QT correction formula.
   • 4-3. A history of risk factors for torsades de pointes (e.g., heart failure, hypokalemia, family history of Long QT Syndrome) or use of concomitant medications that prolong the QT/QTc interval (e.g., class Ia, Ic or III antiarrhythmic drugs, tricyclic antidepressants or phenothiazines)
   • 4-4. Bronchial asthma that may increase the risk associated with study participation, or may interfere with compliance of the protocol as judged by the PI.
   • 4-5. Renal dysfunction (eGFR < 60 ml/min/1.73m2 and/or creatinine > 1.5x ULN), or patients is planned to accept any renal replacement therapy during treatment visits.
   • 4-6. Diagnosed with hyperthyroidism or receiving treatment for hyperthyroidism. Has unstable thyroid function as judged by the PI (e.g. TSH > 5.0 mIU/L).
   • 4-7. Traumatic injuries, clinically significant hemorrhage/bleeding, or clinically significant gastrointestinal bleeding within 8 weeks.
   • 4-8. Major cardiovascular disease, including stroke and transient ischemic attack (TIA).
   • 4-9. Known homocystinuria.
5. Any of the following laboratory findings:
   • 5-1. WBC < 3000 /μL
   • 5-2. Platelets < 100,000/μL
   • 5-3. Hgb < 8.5 g/dL
   • 5-4. AST > 5x ULN
   • 5-5. ALT > 5x ULN
6. Performance status Eastern Cooperative Oncology Group (ECOG) of 2 or more.
7. Patients whose blood vessel are too difficult to perform TACE procedure as judged by PI.
8. TACE procedure would be performed in areas of the liver where bile ducts are dilated as judged by PI.
9. Prominent Hepatic arteriovenous (AV) shunt, as judged by PI.
10. Non-targeted area may be endangered during TACE procedure, as judged by PI.
11. Patients, who have ever accepted TACE therapy, and cannot gain extra benefits from further embolization treatment.
12. Number of HCC tumors more than 10.
13. Allergy or contraindication to iodine, Lipiodol, allowed contrast agents, allowed Gelfoam suppositories or allowed artery hemostats.
14. Pregnant females or lactating females.
15. Male or female subjects with fertility who are unwilling to perform highly effective contraception method.
16. Subjects who, in the opinion of the investigator, are not suitable to participate in the trial for whatever reason.