HepaSphere/Quadrasphere Microspheres for Delivery of Doxorubicin for the Treatment of Hepatocellular Cancer
Condition: Hepatocellular Carcinoma
MeSH terms: Carcinoma; Carcinoma, Hepatocellular
Intervention: HepaSphere/QuadraSphere Microspheres; PVA, lipiodol, doxorubicin
Intervention description: HepaSphere/QuadraSphere Microspheres loaded with doxorubicin; Conventional TACE procedure using PVA, lipiodol and doxorubicin
Intervention MeSH terms: Doxorubicin; Ethiodized Oil
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Participants are randomized 1:1 to receive either 1. A Conventional TACE (Trans Arterial Chemoembolization) procedure using PVA, lipiodol and doxorubicin (cTACE), or 2. HepaSphere/QuadraSphere Microspheres loaded with doxorubicin for Trans Arterial Chemoembolization (hqTACE). Participants in both treatment arms will be followed for overall survival, the primary study endpoint.
Masking: Double (Participant, Outcomes Assessor)
Masking description: Participants are blinded to the treatment they are randomized to (cTACE or hqTACE). Central Reviewers (two interventional radiologists) will evaluate study participant's liver MRIs to assess the tumor response. The Central Reviewers will be blinded to the treatment the participant received.
Enrollment: 235.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Hepatocellular carcinoma; TACE; HepaSphere Microspheres; QuadraSphere Microspheres; Doxorubicin

Summary:

      The purpose of this study is to evaluate overall survival in patients diagnosed with
      hepatocellular cancer (HCC) treated with HepaSphere/QuadraSphere Microspheres loaded with
      chemotherapeutic agent doxorubicin compared to conventional transarterial chemoembolization
      with particle PVA, lipiodol, and doxorubicin.
    

Eligibility criteria:

        Inclusion Criteria:

        Patients must meet all of the following inclusion criteria in order to be entered into the
        study:

          1. Age 18 or older

          2. Patient has signed informed consent

          3. Patient must have a diagnosis of hepatocellular cancer confirmed by at least one of
             the following:

        i. Histological confirmation ii. Magnetic resonance imaging (MRI) result with early
        enhancement and delayed enhancement washout of at least one solid liver lesion > 1 cm.
        Patient must also have evidence of cirrhosis or have chronic hepatitis B.

        iii. Contrast enhanced computed tomography (CT) with early enhancement and delayed
        enhancement washout of at least one solid liver lesion > 1cm. Patient must also have
        evidence of cirrhosis or have chronic hepatitis B.

        d. Patient must not be suitable for treatment by resection or percutaneous ablation at time
        of study entry.

        Patients not suitable for ablation due to lesion location may be enrolled

        e. Patient MUST meet at least ONE of the following criteria:

        i. Stage Child-Pugh B 7 ii. Recurrent HCC iii.Performance status ECOG 1

        f. Patient has a life expectancy of at least 6 months

        g. Absence of occlusive thrombus to the main portal trunk

        Exclusion Criteria:

        If patients meet any of the following criteria they may not be entered into the study:

          1. Current or previous treatment with chemo- or radiation therapy or sorafenib

          2. Previous treatment with any form of transarterial embolization for HCC

          3. Patients with current or history of any other cancer except non-melanomatous skin
             cancer

          4. Female patients who are pregnant, breastfeeding, or premenopausal and not using an
             effective method of contraceptive

          5. Performance status ECOG > 2

          6. Child-Pugh scores >7

          7. Active gastrointestinal bleeding

          8. Evidence of uncorrectable bleeding diathesis

          9. Extra-hepatic spread of the HCC

         10. Total Bilirubin > 3 mg/dL

         11. >50% tumor involvement of the liver

         12. Infiltrative or diffuse HCC

         13. Encephalopathy not adequately controlled medically

         14. Presence of ascites not controlled medically

         15. Presence of medically relevant localized or systemic infection, other than hepatitis
             B, C, D, E or G

         16. Any contraindication for MRI (eg. metallic implants)

         17. Allergy to contrast media that cannot be managed with prophylaxis

         18. Allergy to iodized oil

         19. Any contraindication to arteriography

         20. Any contraindication for doxorubicin administration, including the following:

        i. White Blood Cell count (WBC) <3000 cells/mm₃

        ii. Absolute Neutrophil <1500 cells/mm₃

        iii. Cardiac ejection fraction <50%

        iv. Other condition deemed exclusionary by physician

        u. Any contraindication for hepatic embolization, including the following:

        i. Porto-systemic shunt, or an arteriovenous shunt that cannot be adequately closed prior
        to chemoembolization

        ii. Hepatofugal blood flow

        iii. Serum creatinine > 2mg/dL

        iv. Uncorrectable impaired clotting

          1. Platelet <50,000/mm₃

          2. International Normalized Ratio (INR) > 1.4

          3. Activated Prothrombin Time (aPTT) less than 21 or greater than 40

             v. AST > 5X upper limit of normal for lab

             vi. ALT > 5X upper limit of normal for lab