A Study of PTS100 in Primary HCC Patients

This study is being performed to evaluate the efficacy and safety of 30% PTS100 of total tumor volume as intra-tumoral injection therapy in primary Hepatocellular Carcinoma patients who are ineligible for operation or local regional therapy.

BCLC stage B patients who are ineligible for operational or current locoregional therapy. Enrolled patients are assigned to 30% of total tumor volume. PTS100 is administrated via intratumoral injection. The required total dose is given in separate injection days, with maximal daily dose up to 10 mL at first IP administration, and is adjusted based on each patient's tolerability along the treatment. The treatment course lasts up to completion of the total dose, and the efficacy is evaluated 28 days afterwards.

Eligibility Criteria:
Inclusion Criteria:

* Male or female, ≥ 20 years and ≤ 80 years of age.
* Patients with clinically confirmed primary HCC following American Association for the Study of Liver Diseases (AASLD, Appendix 1) guidance:

  1. Cyto-histological evidence, or
  2. Coincident imaging evidence using computerized tomography (CT) or magnetic resonance imaging (MRI)
* Based on investigator discretion, patients who are diagnosed at Barcelona Clinic Liver Cancer (BCLC) stage B and are ineffective or unsuitable for resection, immediate liver transplantation, Trans Arterial Chemoembolization (TACE), or current local ablative treatment and meet all of the following conditions at study entry:

  1. Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 1.
  2. Child Pugh score class A or B.
* Patients with at least one measurable lesion with size ≥ 1 cm.
* Patients with cumulative total treated tumor volume ≤ 366 cm3 and ≤ 4 target tumors.
* Patients with adequate bone marrow, liver and renal function within 28 days prior to study entry, as defined by the following:

  1. Hemoglobin \> 10.0 g/dl.
  2. Absolute neutrophil count (ANC) \> 1,500/mm3.
  3. Platelet count \> 80k/mm3 correctable by component therapy.
  4. Albumin ≥ 3 g/dl.
  5. Total bilirubin \< 2 mg/dL.
  6. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) \< 5 x upper normal limit (UNL).
  7. Blood urea nitrogen (BUN) and serum creatinine \< 1.5 x UNL.
  8. International normalized ratio (INR) \< 1.5 or prothrombin time (PT) \< 15 seconds.
* Patients with life expectancy \> 3 months as judged by investigator.
* Patients who understand and comply to the study procedure and be willing to provide a written informed consent form.

Exclusion Criteria:

* Infiltrative HCC or tumor burden ≥ 50% of liver parenchyma.
* Patients with cumulative total treated tumor volume \> 366 cm3 or more than 4 target tumors.
* Any target tumor exceeds 8.8 cm in diameter.
* The treated tumor is located in close proximity to another organ (e.g. gall bladder, liver capsule, diaphragm ) or major blood vessel and less than 0.5 cm in distance .
* Presence of metastasis or vascular invasion.
* Systemic chemotherapy treatment for HCC within 12 weeks prior to study entry.
* Major surgery within 4 weeks prior to study entry (e.g. thoracolaparotomy is not allowed, but noninvasive surgery, e.g. biopsy, is allowed).
* Use of any investigational drugs, biologics, or devices within 4 weeks prior to study entry or planned use during the course of study.
* Any other severe disease (e.g. active infection, uncontrolled diabetes mellitus, severe heart dysfunction or angina, gastric ulcer, active auto-immune disease) judged by the investigator to limit subject participation in the study.
* Female subjects who are pregnant or lactating. Women of childbearing potential must have a negative urine pregnancy test performed within seven days prior to the start of study drug and agree to practice medically acceptable contraceptive regimen from screening until at least 28 days after the study treatment. Patients who are postmenopausal for at least 1 year (\> 12 months since the last menstrual cycle) or were surgically sterilized do not require the pregnancy test.
* Known or suspected allergy and/or hypersensitivity to any of the ingredients of PTS100.
* Any target lesion blocked by bile ducts or important blood vessels, judged by investigator, that is difficult to conduct intratumoral injection.
* Any condition, judged by investigator, that shows subjects are not suitable for participation.