A Phase III PI-88 in the Adjuvant Treatment of Subjects With Hepatitis Virus Related HCC After Surgical Resection
Condition: Cancer; Liver Cancer; Hepatocellular Carcinoma
MeSH terms: Carcinoma, Hepatocellular; Liver Neoplasms
Intervention: PI-88; Placebo
Intervention description: Lyophilized powder reconstituted to provide 160 mg of PI-88; Lactose lyophilized powder
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 520.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Hepatocellular Carcinoma; PI-88; Phase III; Adjuvant Therapy; Hepatoma; Liver Cancer

Summary:

      The purpose of this study is to determine if PI-88 is effective and safe in patients who have
      had surgery to remove primary liver cancer.
    

Eligibility criteria:

        Key inclusion criteria:

          1. Histologically-proven primary hepatocellular carcinoma with curative resection
             performed in the 4 - 6 weeks prior to randomization.

          2. Age ≥ 18 years.

          3. Written, signed and dated informed consent to participate in study

          4. ECOG performance status 0 to 1

          5. Child Pugh score ≤ 8

          6. Platelet count ≥ 80 x 109 cells/liter

          7. PT-INR ≤ 1.3

          8. aPTT ≤ upper limit of normal

        Key exclusion criteria:

          1. Pathological confirmation of single tumor < 2 cm in diameter which obtained from the
             most recent hepatectomy.

          2. History of immune-mediated thrombocytopenia other platelet abnormalities or other
             hereditary or acquired coagulopathies, or laboratory evidence of anti-heparin
             antibodies, or any previous history of having tested positive for anti-heparin
             antibodies.

          3. Any evidence of tumor metastasis or co-existing malignant disease

          4. Any prior recurrence of HCC or any liver resection prior to the most recent procedure

          5. Clinically significant non-malignant disease including, but not limited to, surgery
             within 6 weeks of randomization (apart from liver resection and re-operation for
             complications of liver resection), active clinically significant infection within 6
             weeks prior to randomization, myocardial infarction within 6 months prior to
             randomization, cerebrovascular event within 12 months prior to randomization or
             clinically-significant gastrointestinal bleeding within 12 months prior to
             randomization. Subjects who have experienced post-operative complications of liver
             resection may be enrolled providing that such complications are fully resolved at the
             time of screening.

          6. Subjects with uncontrolled infection or serious infection within the past 4 weeks.

          7. History of prior HCC therapy including chemotherapy, radiotherapy, molecular targeting
             agents, vaccines, transarterial embolization (TAE), transarterial chemoembolization
             (TACE), liver transplantation or surgical resection prior to the most recent
             hepatectomy, at any time prior to randomization. This includes pre-, peri- and
             post-operative treatments. Pre-operative portal vein embolization is permitted.
             Subjects should not be enrolled if, at the time of randomization, it is planned that
             they will subsequently undergo liver transplantation regardless of tumor recurrence.

          8. Concomitant use of aspirin (> 150 mg/day), vitamin K antagonists (other than low-dose
             prophylactic use), heparin within two weeks prior to randomization, or other
             anti-platelet drugs (e.g. abciximab, clopidogrel, dipyridamole, ticlopidine and
             tirofiban). Low dose aspirin (≤ 150 mg/day) and low-dose prophylactic vitamin K
             antagonists (e.g. warfarin ≤ 1 mg/day) are permitted as concomitant medications.

          9. History of allergic, anaphylactic or other significant adverse reaction to
             radiographic contrast media (iodinated or non-iodinated), which cannot be managed by
             pre-treatment with agents such as steroids or anti-histamines, and which, in the
             opinion of the investigator, renders the subject unsuitable for routine CT scanning.
             Subjects who are contra-indicated for CT scanning for other reasons (e.g.
             ferromagnetic implants, profound claustrophobia), should not be enrolled.

         10. Subjects with history of inflammatory bowel disease, any other abnormal bleeding
             tendency, or subjects at risk of bleeding due to open wounds or planned surgery.

         11. Women who are pregnant or breast-feeding or women of child-bearing potential who are
             unable or unwilling to practice a highly effective means of contraception.

         12. Active substance abuse, including alcohol, which, in the opinion of the investigator,
             risks impairing the ability of the subject to comply with the protocol.

         13. Subjects who received other investigational or anti-neoplastic medication within the
             past 4 weeks.

         14. Current participation in any other clinical study or research project which involves
             administration of a pharmaceutical product or experimental treatment, or which
             involves protocol-specified laboratory tests, imaging studies or other investigations.