Details
Description
Inclusion Criteria
Exclusion Criteria
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
Primary Objective- To compare Progression-Free Survival (PFS) of chemoembolization alone to sorafenib in combination with chemoembolization.
- To compare overall survival (OS) of chemoembolization alone to sorafenib in combination with chemoembolization.
- To evaluate extra-hepatic versus intra-hepatic patterns of failure.
- To determine the rates of toxicity related to Sorafenib in combination with chemoembolization.
- Pharmacogenetic and Pharmacokinetic Ancillary (PG0107) Objective: To analyze the pharmacogenetic and pharmacokinetic properties of Sorafenib including angiogenesis, monooxygenases, polymorphisms and MDR.
- ECOG secondary imaging objective: Site vs. Central evaluation of PFS
- 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
- 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
- Patients must have HCC limited to the liver. There must be no clinical or radiographic evidence of extrahepatic HCC.
- Portal Lymphadenopathy IS permitted for patients with HBV or HCV - as lymphadenopathy is commonly associated with hepatitis unrelated to malignancy.
- Staging CT of the Chest and CT or MRI of the Abdomen and Pelvis must have been completed within 4 weeks of study registration.
- Patients must have measurable disease as defined in Section 6.1.1 constituting < 50% of liver parenchyma within 4 weeks of registration
- Patients may not have ascites detectable on physical examination.
- Patients must not be candidates for curative resection, orthotopic liver transplantation, or radiofrequency ablation (RFA).
- Patients may have been treated with RFA in the past, but no sooner than 4 weeks before study registration.
- Patients may have undergone previously attempted curative liver resection.
- Patients may NOT have been previously treated with brachytherapy such as Yttrium-90 microsphere.
- Patients may NOT have been previously treated with sorafenib, chemoembolization, or systemic chemotherapy including cytotoxic agents or molecularly targeted agents.
- Branch portal vein invasion by tumor is permitted but patients with main portal vein invasion by tumor are not eligible.
- 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.
- 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.
- Patients must not have any evidence of bleeding diathesis or active gastrointestinal bleeding.
- 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
- Patients must have an ECOG performance status of 0 or 1.
- Patients must have a life expectancy of at least 3 months.
- 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.
- 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.
- Patients must not be taking cytochrome P450 enzyme inducing drugs. Refer to a list of agents listed in Appendix VIII.
- Age ≥ 18 years.
- 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.
- Women of childbearing potential and sexually active males must be strongly advised to use an accepted and effective method of contraception.
- Patients must not have an allergy to iodine or gadolinium contrast that can not be safely controlled with premedication.
- Patient must be able to swallow pills, as study medications can not be crushed.