Phase 2 Study of TAC-101 Combined With Transcatheter Arterial Chemoembolization (TACE) Versus TACE Alone in Japanese Patients With Advanced Hepatocellular Carcinoma
Condition: Advanced Hepatocellular Carcinoma
MeSH terms: Carcinoma; Carcinoma, Hepatocellular
Intervention: TAC-101; Placebo
Intervention description: Participants received TAC-101 20 mg (2 x 10-mg formulated tablets) administered orally every day with approximately 8 oz. water within 1 hour following a morning meal for 14 days followed by a 7-day recovery period, repeated every 21 days.; Participants received placebo (two matching tablets) at same frequency and duration of active treatment.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 54.0
Sex: All
Minimum age: 20 Years
Healthy volunteers: No

Summary:

      The purpose of this study is to determine whether TAC-101 combined with Transcatheter
      Arterial Chemoembolization (TACE) is more effective than TACE alone in slowing tumor activity
      in patients with advanced hepatocellular carcinoma. The study is also looking at the safety
      of TAC-101 in combination with TACE.
    

Eligibility criteria:

        Inclusion Criteria:

        - A patient must meet all of the following inclusion criteria to be eligible for enrollment
        in this study and before undergoing the first TACE procedure of this study:

          1. Has an HCC diagnosis by histology or by the following non-invasive criteria observed
             either at enrollment or in the past.

               -  One imaging technique (CT scan or magnetic resonance imaging [MRI] both with
                  unenhanced plus hepatic arterial phase and portal venous phases) showing
                  characteristic features in a focal lesion > 20 mm with arterial vascularization.

               -  Two dynamic imaging techniques (CT scan, MRI with unenhanced plus hepatic
                  arterial phase and portal venous phases) showing characteristic features
                  coincidentally in a focal lesion 10-20 mm with arterial vascularization.

          2. Is TACE naïve or has received the most recent TACE procedure at least 120 days before
             signing ICF.

          3. Eligible to receive TACE and being scheduled to receive TACE.

          4. Must be ≥ 20 years of age.

          5. Is not amenable to treatment with curative surgery, transplant, or percutaneous
             ablation, including RFA, percutaneous ethanol injection therapy (PEIT) and
             percutaneous microwave coagulation therapy (PMCT).

          6. Must have lesions in the liver that are confirmed nodular type with demonstrated
             substantial hypervascularity by CT scan or MRI both with unenhanced plus hepatic
             arterial phase and portal venous phases performed prior to first TACE in this study
             with the following tumor features:

               -  If there are ≥ 4 intrahepatic lesions, all lesions can be < 30 mm. or, regardless
                  of the number of lesions, the longest diameter of at least one intrahepatic
                  lesion is ≥ 30 mm).

               -  No vascular invasion in main trunk and first order branch of portal vein.

               -  No extrahepatic tumor spread. The absence of extrahepatic abdominal tumors must
                  be confirmed.

          7. Has adequate organ function as defined by the following criteria: White blood cell
             (WBC) count > 3,000/mm3; Platelet count > 60,000/mm3; Hemoglobin > 8.0 grams
             (g)/deciliter (dL); Aspartate transaminase (AST) < 5 x upper limit of normal (ULN);
             Alanine transaminase (ALT) < 5 x ULN; Total bilirubin < 2.0 mg/dL; Albumin ≥ 2.8 g/dL;
             Serum creatinine ≤ 1.5 mg/dL; International normalized ratio (INR) ≤ 2.0; Triglyceride
             ≤ 2.5 x ULN.

          8. Must have a Child-Pugh classification of ≤ 8.

          9. Must have a Cancer of the Liver Italian Program (CLIP)60 score of 0, 1, 2 or 3
             (Appendix B).

         10. Must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.

         11. Must be willing and able to comply with schedule visits, treatment plans, laboratory
             tests, and other study procedures.

         12. Must provide written informed consent prior to the implementation of any study
             assessment or procedures.

        Exclusion Criteria:

          -  Patients will be excluded from participation in the study if any of the following
             conditions are observed before undergoing the first TACE procedure:

               1. Patient has longest diameter of intrahepatic lesion ≥ 100 mm.

               2. Patient has only infiltration type of HCC.

               3. Patient has extrahepatic metastasis of HCC including regional lymph node
                  metastases (including in lymph nodes and organs).

               4. Patient had systemic chemotherapy (eg, sorafenib, doxorubicin), immunotherapy, or
                  biologic therapy or radiotherapy for HCC, or treatment with TAC-101.

               5. Patient received treatment with any of the following within the specified time
                  frame: Any major surgical procedure within 28 days prior to signing the ICF; Any
                  transfusion, treatment with blood component preparation, albumin preparation, and
                  granulocyte colony stimulating factor (G-CSF) within 14 days prior to signing the
                  ICF; Any local therapy such as alcohol injection, radiofrequency/ultrasound
                  ablation, intraarterial chemotherapy (transcatheter arterial injection) for HCC
                  performed within 28 days prior to signing the ICF; Any investigational agent
                  within 28 days prior to signing the ICF.

               6. Patient has ascites, pleural effusions or pericardial fluid refractory to
                  diuretic therapy.

               7. Patient has clinical symptoms of hepatic encephalopathy.

               8. Patient has active or uncontrolled clinically serious infection excluding chronic
                  hepatitis.

               9. Patient has a history of gastrointestinal (GI) bleeding in last 3 months.

              10. Patient has previous or concurrent malignancy except for in situ carcinoma of the
                  cervix, or other solid tumor treated curatively and without evidence of
                  recurrence for at least 3 years prior to the study.

              11. Patient has uncontrolled metabolic disorders or other nonmalignant organ or
                  systemic diseases or secondary effects of cancer that induce a high medical risk
                  and/or make assessment of survival uncertain.

              12. Patient has any history of deep vein thrombosis (DVT), pulmonary embolism (PE),
                  myocardial infarction (MI), cerebrovascular accident (CVA), transient ischemic
                  attack (TIA), unstable angina pectoris, or any other significant thromboembolic
                  event (TE) during the last 3 years.

              13. Patient has clinically significant electrocardiogram (ECG) abnormality.

              14. Patient has GI disease resulting in an inability to take oral medication.

              15. Patient has known allergy or hypersensitivity to TAC-101, doxorubicin,
                  epirubicin, other anthracyclines, anthracenediones or any of the components used
                  in the study drug formulations.

              16. Patient has known hypersensitivity to iodinated contrast medium.

              17. Patient is receiving therapeutic regimens of anticoagulants. However, use of low
                  dose anticoagulants for prophylactic care of indwelling venous access device is
                  permitted.

              18. Patient is taking medication known or suspected to predispose patient to an
                  increased risk of VTE (eg, oral contraceptives, hormone replacement therapy,
                  megestrol acetate).

              19. Patient is taking azoles or tetracyclines, because of the potential for drug
                  interactions.

              20. Women who intend to become pregnant or are pregnant or lactating and men able to
                  procreate that refuse to use a highly effective method of birth control during
                  treatment with study medication and up to 6 months thereafter.