Study of Peretinoin for Suppressing Recurrence of HCV-positive HCC
Condition: Hepatic Neoplasm Malignant Recurrent
MeSH terms: Neoplasms; Liver Neoplasms; Recurrence
Intervention: NIK-333(peretinoin); Placebo
Intervention description: 600mg (8 x 75mg capsules) orally, twice a day; Placebo (8 x Placebo capsules) orally, twice a day
Phase: Phase 3
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 616.0
Sex: All
Minimum age: 20 Years
Healthy volunteers: No

Summary:

      The purpose of this study is to verify the superiority of NIK-333 (Peretinoin) to placebo in
      inhibiting the recurrence of HCV-positive HCC in patients showing complete cure of the
      disease, with the recurrence-free survival as the primary endpoint, in a multi-center,
      randomized, double-blind, placebo-controlled, parallel-group comparison study.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Patients with HCV-positive HCC who meet the following conditions before radical
             treatment

               -  Patients diagnosed as having typical HCC on dynamic CT,CTA/CTAP, or dynamic MRI
                  (nodule visualized as a high signal intensity area in the arterial phase and as a
                  relatively low signal intensity area in the portal and equilibrium phases)
                  performed within 8 weeks (56 days) before treatment start prior to radical
                  therapy

               -  Patients with the first primary HCC or the first recurrence of primary HCC

          2. Patients who received the radical therapies. The treatment duration (from the start to
             the end of the treatment) should be within 4 weeks (28 days) for each of the radical
             therapies.

          3. Patients showing a complete cure, as confirmed by the dynamic CT images taken from 8
             weeks (56 days) to 12 weeks (84 days) after the end of the treatment show a
             non-stained low-concentration area overlapping the tumor image observed before
             complete cure.

          4. Patients who are able to begin treatment with the study drug within 8 weeks (56 days)
             after dynamic CT to confirm complete cure

          5. Patients confirmed of satisfying the following conditions based on the screening
             performed at subject registration

               -  Positive for serum hepatitis C virus nucleic acid (HCV-RNA)

               -  Grade A on Child-Pugh classification

               -  Platelet count of 50 000/µL or higher

          6. Patients with ECOG Performance Status score of 0 to 1

          7. Patients of the age of 20 years or older at the time of informed consent

        Exclusion Criteria:

          1. Patients positive for HBs antigen

          2. Patients showing vascular invasion of HCC on imaging diagnosis

          3. Patients who have also undergone transcatheter arterial embolization therapy
             (TAE/TACE), transarterial infusion therapy (TAI), and chemolipiodolization in
             combination with the radical therapy

          4. 4 Patients who want to receive antiviral therapy such as concomitant therapy with
             intaferon during the study period

          5. Patients who have received other study drugs, anticancer drugs, or interferons after
             radical therapy

          6. Patients who have hypertension as a complication, and whose blood pressure cannot be
             controlled by drug therapy (systolic blood pressure of 160 mmHg or higher or diastolic
             blood pressure of 100 mmHg or higher, as determined at subject registration)

          7. Patients who have a history of allergy to CT contrast media, and whose participation
             in this study is judged to be inappropriate by the investigator or the subinvestigator

          8. Patients with a history of total gastrectomy

          9. Patients with a history of cardiac arrest

         10. Patients with any of the following laboratory values or complications

               -  Creatinine>= 1.5mg/dL

               -  Albumin urine >= 1000mg/g Creatinine

               -  Cardiac disorder corresponding to CTC-AE grade 3 in severity

               -  HbA1c >= 7.4 under treatment with insulin

               -  Autoimmune disease or asthma being treated with oral steroid

         11. Patients confirmed of having another malignant neoplasm or who had undergone a radical
             therapy of HCC within the past 5 years to treat another malignant neoplasm (however,
             this does not apply to endoscopic resection and resection of intraepithelial
             carcinoma)

         12. Patients who are pregnant, who have a possibility of being pregnant or who have a
             desire to become pregnant during the study period

         13. Lactating women

         14. Patients who have a history of allergy to retinoid-related substances (vitamin A,
             etc.) in the past

         15. Patients who participated in another clinical study within past 6 months