Phase 3 Study of ThermoDox With Radiofrequency Ablation (RFA) in Treatment of Hepatocellular Carcinoma (HCC)
Condition: Hepatocellular Carcinoma
MeSH terms: Carcinoma; Carcinoma, Hepatocellular
Intervention: ThermoDox; 5% Dextrose Solution
Intervention description: Thermally Sensitive Liposomal Doxorubicin 50 mg/m2 Single 30 minute intravenous infusion; Single 30 minute intravenous infusion
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 701.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: hepatocellular carcinoma; liver cancer

Summary:

      The purpose of this study is to determine whether ThermoDox, a thermally sensitive liposomal
      doxorubicin, is effective in the treatment of non-resectable hepatocellular carcinoma when
      used in conjunction with radiofrequency ablation (RFA).
    

Eligibility criteria:

        Inclusion Criteria:

          -  Diagnosed hepatocellular carcinoma (HCC)

          -  No more than 4 HCC lesions with at least one ≥ 3.0 cm and none > 7.0 cm in maximum
             diameter, based on diagnosis at screening.

          -  If a subject has a large lesion (5.0 - 7.0 cm), any other lesions must be less than
             5.0 cm.

          -  Anticipated ablation volume will be no larger than either removal of 3 hepatic
             segments or removal of more than 30% of total liver volume (as per maximum surgical
             limit).

          -  If additional lesions are discovered during the laparoscopic or open treatment
             procedure, that were undetectable by CT at screening, the size and location of the
             lesion(s) will be recorded in the CRF and the lesions will be treated at the
             discretion of the physician and guided by the local standard of care. The subject will
             remain on study if all lesions are treated. If any lesions cannot be completely
             ablated within two treatment attempts the subject will be considered a treatment
             failure.

          -  Study subjects being considered for re-treatment after disease progression may have
             more than 4 lesions.

          -  Male or female 18 years of age or older.

          -  Are willing to sign an informed consent form, indicating that they are aware of the
             investigational nature of this study that is in keeping with the policies of the
             institution.

          -  Be an appropriate candidate for receiving RFA as a medically indicated treatment as
             evaluated by the following factors:

               -  Number of lesions

               -  Size of lesions

               -  Overall health of liver

               -  Not a candidate for surgical resection

          -  Have an echocardiogram revealing a Left Ventricular Ejection Fraction (LVEF) ≥ 50%.
             Measurements with a multiple gated acquisition (MUGA) scan are allowed if an
             echocardiogram cannot be performed. The same method of measurement should be used to
             evaluate ejection fraction (EF) of the subject for the duration of the study.

          -  Willing to return to the study site for their study visits.

          -  Have life expectancy of ≥ 4 months.

          -  Have Child-Pugh Class A or B liver disease without encephalopathy or/and ascites.

        Exclusion Criteria:

          -  Have serious medical illnesses including, but not limited to, congestive heart
             failure, myocardial infarction or cerebral vascular accident within the last six
             months, or life threatening cardiac arrhythmias.

          -  Is scheduled for liver transplantation.

          -  Have previously received any treatment for HCC (except for study subjects being
             considered for completion of treatment or re-treatment).

          -  Have previously received any doxorubicin (study subjects being considered for
             completion of treatment or re-treatment may have received ThermoDox previously).

          -  Have extrahepatic metastasis.

          -  Are pregnant or breast-feeding. In women of childbearing potential, a negative
             pregnancy test (serum) is required prior to study treatment.

          -  Women of childbearing potential who are not practicing an acceptable form of birth
             control (i.e. diaphragm, cervical cap, condom, surgical sterility or birth control
             pills. Women whose partner has undergone a vasectomy must use a second form of birth
             control).

          -  Have any known allergic reactions to any of the drugs or liposomal components or
             intravenous imaging agents to be used in this study.

          -  Have portal or hepatic vein tumor invasion/thrombosis.

          -  Have INR > 1.5 times the institution's upper normal limit (UNL), except in subjects
             who are therapeutically anticoagulated for medical conditions unrelated to HCC such as
             atrial fibrillation. Subjects may be re-screened after condition is treated or
             anticoagulant is withheld.

          -  Have platelet count < 75,000/mm3, absolute neutrophil count < 1500/mm3, or Hgb < 10.0
             g/dL (unless the hemoglobin value has been stable, the subject is cardiovascularly
             stable, asymptomatic and judged able to withstand the RFA procedure).

          -  Have serum creatinine ≥ 2.5 mg/dL or calculated creatinine clearance (CrCl) ≤ 25.0
             mL/min.

          -  Have serum bilirubin > 3.0 mg/dL.

          -  Have serum albumin < 2.8 g/dL.

          -  Have body temperature >1010F (38.30C) immediately prior to study treatment.

          -  Have contraindications to receiving doxorubicin HCl.

          -  Are being treated with other investigational agents.

          -  Use of an investigational drug within 30 days or 5 half-lives, whichever is longer,
             preceding the first dose of study medication (study subjects being considered for
             completion of treatment or re-treatment may have received ThermoDox previously).

          -  Have other concurrent malignancy (subjects with treated squamous cell carcinoma of the
             skin or basal cell carcinoma of the skin may be included), evidence of extrahepatic
             cancer from their primary malignancy, or ongoing, medically significant active
             infection.

          -  Documented HIV positive.

          -  NYHA class III or IV functional classification for heart failure.

          -  Evidence of hemachromatosis.

          -  Have history of contrast-induced nephropathy.