Study of TAC-101 as Second Line Treatment in Patients With Advanced Hepatocellular Carcinoma Who Received Sorafenib as First Line Therapy
Condition: Hepatocellular Carcinoma
MeSH terms: Carcinoma; Carcinoma, Hepatocellular
Intervention: TAC-101; Placebo
Intervention description: Participants were randomized to TAC 101 received TAC 101 20 mg (administered as 2 10 mg formulated tablets) PO daily with approximately 240 mL (8 oz) of water under fed conditions (no later than 1 hour after a meal) for 14 days followed by a 7 day recovery period. This cycle was repeated every 21 days.; Participants randomized to placebo received 2 placebo tablets (identical in appearance to the TAC 101 tablets) administered PO daily with approximately 240 mL (8 oz) of water under fed conditions (no later than 1 hour after a meal) in a regimen identical to that for TAC 101.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 52.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      The purpose of this study is to determine whether TAC-101 as a second line therapy for
      participants who received Sorafenib as first line therapy is effective in slowing tumor
      activity in patients with advanced hepatocellular carcinoma. The study is also looking at the
      safety of TAC-101 following treatment with Sorafenib.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Provide written informed consent prior to performance of any study procedures.

          -  Is at least 18 years of age.

          -  Have a diagnosis of advanced unresectable histologically confirmed HCC (excluding
             fibrolamellar carcinoma).

          -  Have discontinued from first line treatment with sorafenib monotherapy for any reason
             (ie, tumor disease progression, intolerance) at least 14 days prior to planned
             randomization but have not received any second line treatment for HCC.

          -  Have recovered from any significant sorafenib-related treatment toxicities prior to
             randomization (Grade 1).

          -  Have at least 1 target lesion that is viable (has vascularization) and can be
             accurately measured according to RECIST.

          -  Patients who have received local therapy prior to sorafenib administration (radiation,
             surgery, hepatic arterial embolization, chemoembolization, RFA, percutaneous ethanol
             injection [PEI] or cryoablation) are eligible. Local therapy must be completed at
             least 4 weeks prior to the baseline scan.

          -  Have ECOG score of 0, 1, or 2.

          -  Child-Pugh score <8.

          -  Have adequate organ function defined as:

               -  Platelet count great than 50, less than 109/L;

               -  Hemoglobin 8.0 g/dL;

               -  Total bilirubin 3 mg/dL;

               -  Alanine transaminase (ALT) and aspartate aminotransferase (AST) less than or
                  equal to 5 X ULN;

               -  Serum creatinine 1.5 X ULN;

               -  PT-international normalized ratio (INR) 2.3 or PT 6 seconds above control

               -  Total white blood cell (WBC) count 2.0 109/L

          -  Is able to take medications orally (eg, no feeding tube).

          -  Women of childbearing potential must have a negative pregnancy test (urine or serum)
             prior to randomization and within 2 days prior to starting the study drug. Females
             must agree to adequate non-estrogenic birth control if conception is possible during
             the study; and males must agree to adequate birth control during the study and up to 6
             months after the discontinuation of study medication.

        Exclusion Criteria:

          -  History of DVT, PE, myocardial infarction (MI), CVA, transitory ischemic attack (TIA),
             or any other significant TE during the last 3 years.

          -  Have clinically significant symptoms of hepatic encephalopathy or known brain
             metastasis.

          -  Patients who have had clinically significant acute gastrointestinal bleeding as a
             result of portal vein hypertension within 4 weeks prior to randomization are excluded;
             however, patients with a history of acute gastrointestinal bleeding that have received
             appropriate treatment, ie, ligation of varices, are eligible.

          -  Are receiving therapeutic regimens of anticoagulants, with the exception of
             prophylaxis care of indwelling venous access devices.

          -  Have received a liver transplant.

          -  Are taking prohibited medication.

          -  Have received a previous systemic therapy (including investigational agents) other
             than sorafenib (see Inclusion Criterion 4) for treatment of HCC. Patients
             participating in surveys or observational studies are eligible to participate in this
             study.

          -  Have had treatment with any of the following within the specified timeframe prior to
             randomization:

               -  Any sorafenib within the 14 days prior to randomization.

               -  Major surgery within the 4 weeks prior to randomization.

               -  Any transfusion, treatment with blood component preparation, received.
                  erythropoietin , albumin preparation, and granulocyte colony-stimulating factor
                  (G CSF) within the 2 weeks prior to randomization.

          -  Has a serious illness or medical condition(s) including, but not limited to the
             following:

               -  Known gastrointestinal disorder, including malabsorption, chronic nausea,
                  vomiting, or diarrhea present to the extent that it might interfere with oral
                  intake and absorption of the study medication.

               -  Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome
                  (AIDS)-related illness.

               -  Previous or concurrent malignancy except for basal cell carcinoma and/or 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.

               -  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.

               -  Has active or uncontrolled clinically serious infection excluding chronic
                  hepatitis.

               -  Other severe acute or chronic medical or psychiatric condition or laboratory
                  abnormality that may increase the risk associated with study participation or
                  study drug administration, or may interfere with the interpretation of study
                  results, and in the judgment of the Investigator would make the patient
                  inappropriate for entry into this study (eg, active urinary tract infection).

               -  Known allergy or hypersensitivity of TAC 101 and any other components used in the
                  TAC 101 tablet.