Details

Details

Title A Phase 3 Randomized Trial of Chemoembolization with or without Sorafenib in unresectable hepatocellular carcinoma (HCC) in patients with or without vascular invasion

IRB E1208

CC 13-518

Hospital Main Campus

Disease Liver

Drug Sorafenib

Description

Description

Primary Objective
  1. To compare Progression-Free Survival (PFS) of chemoembolization alone to sorafenib in combination with chemoembolization.
Secondary Objectives
  1. To compare overall survival (OS) of chemoembolization alone to sorafenib in combination with chemoembolization.
  2. To evaluate extra-hepatic versus intra-hepatic patterns of failure.
  3. To determine the rates of toxicity related to Sorafenib in combination with chemoembolization.
  4. Pharmacogenetic and Pharmacokinetic Ancillary (PG0107) Objective: To analyze the pharmacogenetic and pharmacokinetic properties of Sorafenib including angiogenesis, monooxygenases, polymorphisms and MDR.
  5. ECOG secondary imaging objective: Site vs. Central evaluation of PFS
  6. Correlative Imaging Science Objectives:
    • To determine the inter-reader concordance for response characterization at four and eight months by the European Association for the Study of Liver (EASL) criteria.
    • To determine the value of objective tumor response at four and eight months by the EASL criteria to predict PFS (by RECIST) and OS.
    • To evaluate the effects of intra-hepatic vs. extra-hepatic progression on OS.
Inclusion Criteria

Inclusion Criteria

  1. Patients must have a diagnosis of hepatocellular carcinoma by at least one criterion listed below:
    • Histologically confirmed
    • Magnetic Resonance Imaging (MRI) or Computerized Tomography (CT) consistent with liver cirrhosis AND at least one solid liver lesion > 2cm with early enhancement and delayed enhancement washout regardless of alpha-feto protein levels (AFP).
    • AFP > 400ng/mL AND evidence of at least one solid liver lesion > 2cm regardless of specific imaging characteristics on CT or MRI
  2. Patients must have HCC limited to the liver. There must be no clinical or radiographic evidence of extrahepatic HCC.
  3. Portal Lymphadenopathy IS permitted for patients with HBV or HCV - as lymphadenopathy is commonly associated with hepatitis unrelated to malignancy.
  4. Staging CT of the Chest and CT or MRI of the Abdomen and Pelvis must have been completed within 4 weeks of study registration.
  5. Patients must have measurable disease as defined in Section 6.1.1 constituting < 50% of liver parenchyma within 4 weeks of registration
  6. Patients may not have ascites detectable on physical examination.
  7. Patients must not be candidates for curative resection, orthotopic liver transplantation, or radiofrequency ablation (RFA).
  8. Patients may have been treated with RFA in the past, but no sooner than 4 weeks before study registration.
  9. Patients may have undergone previously attempted curative liver resection.
  10. Patients may NOT have been previously treated with brachytherapy such as Yttrium-90 microsphere.
  11. Patients may NOT have been previously treated with sorafenib, chemoembolization, or systemic chemotherapy including cytotoxic agents or molecularly targeted agents.
  12. Branch portal vein invasion by tumor is permitted but patients with main portal vein invasion by tumor are not eligible.
  13. Patients must have Child-Pugh score of A or B7 within 4 weeks prior to study registration. Please Refer to Appendix IX for Child-Pugh scoring.
  14. Patients must have the following baseline laboratories obtained within 4 weeks prior to study registration:
    • Serum Total Bilirubin ≤ 2.0 mg/dL.
    • Alkaline Phosphatase, AST, ALT < 5x ULN.
    • Serum Creatinine ≤ 1.5 mg/dL
    • Platelet count ≥ 50,000/mm3.
  15. Patients must not have any evidence of bleeding diathesis or active gastrointestinal bleeding.
  16. Patients must have no clinical signs of heart failure and meet New York Heart Association functional classification I or II defined as:
    • Class I - Patients with no limitation of activities; they suffer no symptoms from ordinary activities.
    • Class II - Patients with slight, mild limitation of activity; they are comfortable with rest or with mild exertion
  17. Patients must have an ECOG performance status of 0 or 1.
  18. Patients must have a life expectancy of at least 3 months.
  19. Patients must not be known to be HIV positive; drug-drug interactions with study medication and HIV medications is not well-characterized and could lead to unwanted side effects.
  20. Patients must not have other uncontrolled intercurrent illnesses excluding HBV or HCV, including, but not limited to: uncontrolled hypertension, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia or psychiatric illness/addictive disorders that would limit compliance with study requirements.
    • Uncontrolled hypertension is defined as optimally treated baseline blood pressure that exceeds 150/90 mm Hg.
  21. Patients must not be taking cytochrome P450 enzyme inducing drugs. Refer to a list of agents listed in Appendix VIII.
  22. Age ≥ 18 years.
  23. Women must not be pregnant or breast-feeding due to teratogenic effects of agents used in this trial. All females of childbearing potential must have a blood test or urine study within 2 weeks prior to registration to rule out pregnancy.
  24. Women of childbearing potential and sexually active males must be strongly advised to use an accepted and effective method of contraception.
  25. Patients must not have an allergy to iodine or gadolinium contrast that can not be safely controlled with premedication.
  26. Patient must be able to swallow pills, as study medications can not be crushed.
Exclusion Criteria

Exclusion Criteria

Exclusion Criteria Not Available