Glypican 3-Specific Chimeric Antigen Receptor Expressing T Cells for the Treatment of Unresectable, Metastatic, or Recurrent Liver Cancer

Inclusion Criteria

• PROCUREMENT: Histology-proven HCC which is unresectable, recurrent and/or metastatic
• PROCUREMENT: Barcelona Clinic Liver Cancer Stage A, B or C
• PROCUREMENT: GPC3-positive HCC * GPC3 expression will be evaluated by standard immunohistochemistry (IHC). A tumor is considered GPC3 positive when the staining is grade 2 (> 25% positive tumor cells) or above with an intensity score of 2 or above on a scale of 0 to 4
• PROCUREMENT: Age >= 18 years
• PROCUREMENT: Karnofsky score > 60%
• PROCUREMENT: Life expectancy >= 12 weeks
• PROCUREMENT: Child-Pugh-Turcotte score < 8
• PROCUREMENT: Informed consent explained to, understood by and signed by patient/guardian. Patient/guardian given copy of informed consent
• TREATMENT: Histology-proven HCC which is unresectable, recurrent and/or metastatic
• TREATMENT: Barcelona Clinic Liver Cancer Stage A, B or C
• TREATMENT: GPC3-positive HCC * GPC3 expression will be evaluated by standard immunohistochemistry (IHC). A tumor is considered GPC3 positive, when the staining is grade 2 (> 25% positive tumor cells) or above with an intensity score of 2 or above on a scale of 0 to 4
• TREATMENT: Age >= 18 years
• TREATMENT: Life expectancy of >= 12 weeks
• TREATMENT: Karnofsky score >= 60%
• TREATMENT: Child-Pugh-Turcotte score < 8
• TREATMENT: Creatinine clearance (as estimated by Cockcroft Gault) >= 60 ml/min
• TREATMENT: Serum aspartate aminotransferase (AST) < 5 times upper limit of normal (ULN)
• TREATMENT: Total bilirubin < 3 times ULN for age
• TREATMENT: Institutional normalized ratio (INR) =< 1.7
• TREATMENT: Absolute neutrophil count > 500/ul
• TREATMENT: Platelet count > 20,000/ul (can be transfused)
• TREATMENT: Hemoglobin (Hgb) >= 7.0 g/dl (can be transfused)
• TREATMENT: Pulse oximetry > 90% on room air
• TREATMENT: Recovered from acute toxic effects of all prior antineoplastic drugs before entering this study (including investigational drugs) based on the enrolling physician’s assessment (if some effects of chemotherapy are expected to last long term, patient is eligible if meeting other eligibility criteria)
• TREATMENT: Sexually active patients must be willing to utilize one of the more effective birth control methods for 3 months after the T-cell infusion
• TREATMENT: Available autologous transduced T cell product
• TREATMENT: Informed consent explained to, understood by and signed by patient/guardian. Patient/guardian given copy of informed consent

Exclusion Criteria

• PROCUREMENT: History of hypersensitivity reactions to murine protein-containing products OR presence of human anti-mouse antibody (HAMA) prior to enrollment (only patients who have received prior therapy with murine antibodies)
• PROCUREMENT: History of liver transplantation
• PROCUREMENT: Known human immunodeficiency virus (HIV) positivity
• PROCUREMENT: Active bacterial, fungal or viral infection (except hepatitis B or hepatitis C virus infections)
• PROCUREMENT: Severe previous toxicity from cyclophosphamide or fludarabine
• TREATMENT: Eligible for complete tumor resection or liver transplantation
• TREATMENT: Pregnancy or lactation (for women at child-bearing age, birth control is required)
• TREATMENT: Hepatic encephalopathy
• TREATMENT: Uncontrolled infection
• TREATMENT: Systemic steroid treatment (>= 0.5 mg prednisone equivalent/kg/day)
• TREATMENT: Known HIV positivity
• TREATMENT: Active bacterial, fungal or viral infection (except hepatitis B or hepatitis C virus infections)
• TREATMENT: History of liver transplantation
• TREATMENT: Heart failure of class III-IV and/or C-D per New York Heart Association (NYHA) Criteria
• TREATMENT: History of hypersensitivity reactions to murine protein-containing products OR presence of human anti-mouse antibody (HAMA) prior to enrollment (only patients who have received prior therapy with murine antibodies)
• TREATMENT: Severe previous toxicity from cyclophosphamide or fludarabine