Virtual GRID Stereotactic Body Radiation Therapy for the Treatment of Locally Advanced, Unresectable or Metastatic Hepatocellular Carcinoma

Inclusion Criteria

• Ability of participant OR legally authorized representative (LAR) to understand this study, and participant or LAR willingness to sign a written informed consent
• Males and females age >= 18 years
• Eastern Cooperative Oncology Group (ECOG) performance status 0 - 1
• Histologically confirmed hepatocellular carcinoma (HCC) or mixed HCC and cholangiocarcinoma either locally advanced or metastatic
• Not a candidate for surgical resection, or transplant
• Child Pugh A – B7 liver function scale classification 14 days prior to entry
• Unresectable, locally-advanced or metastatic hepatocellular carcinoma. Meets normal liver and adjacent organ radiation dose constraints, which corresponds to tumor sizes 4 - 12 cm in diameter. Tumors that are larger than 12cm, or tumors that are contiguous and in aggregate measuring 4cm or greater are permitted provided radiation dose constraints to adjacent normal tissue are met per radiation dose constraint
• Women of childbearing potential must have a negative serum pregnancy test 48 hours prior to initiating study intervention. Women of child-bearing potential and men with partners of child-bearing potential must agree to practice sexual abstinence, or to use an acceptable form of contraception for the duration of study participation, and for at least 12 months following completion of therapy
• Men of child-bearing potential must agree not to donate sperm while on this study and for at least 12 months after their last study treatment
• Hemoglobin >= 8 g/dL (The use of transfusion is acceptable)
• Absolute neutrophil count >= 1.0 K/UL
• Platelets >= 50 K/UL
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 6 times upper limit of normal (ULN)
• Albumin >= 2.9 g/dL
• Prothrombin/international normalized ratio (INR) =< 1.7
• Creatinine < 1.5x ULN or creatinine clearance > 60 mL/min
• Total bilirubin =< 3.0
• Gastro-intestinal varices, if present, must be < grade 2, prior grade 3 or higher varices that were treated with banding are allowed at principal investigator (PI) discretion. If clinically indicated, a standard care esophageal gastric duodenoscopy (EGD) is recommended to rule out uncontrolled varices. NOTE: EGD is not required for enrollment
• Documented virology status of hepatitis, as confirmed by hepatitis B virus (HBV) / hepatitis C virus (HCV) serology test at the start of standard care planning. Patients with known hepatitis are allowed on this study provided they meet all other eligibility criteria. Concomitant therapy for hepatitis is permitted at the principal investigator’s discretion. NOTE: The dates of virology documentation can exceed the screening window and will not require repeat testing at the discretion of the principal investigator
• No known history or suspected human immunodeficiency virus (HIV) * Note that patients who are HIV positive are eligible, provided they are under treatment with highly active antiretroviral therapy (HAART) and have a CD4 count ≥ (350) cells/microliter, and no known detectable viral load, at the time of study entry * Note also that HIV testing is not required for eligibility for this protocol

Exclusion Criteria

• Hepatocellular carcinoma (HCC) or other mixed subtype (fibrolamellar HCC, or sarcomatoid HCC) amenable to curative surgery or transplant
• Diagnosed with a psychiatric illness or is in a social situation that would limit compliance with study requirements
• Is pregnant or breastfeeding
• Prior abdominal radiation, including prior arterial Yttrium therapy
• History of autoimmune disease
• Concurrent active secondary malignancy, excluding indolent cancers such as treated cutaneous malignancies or treated chronic lymphocytic leukemia, or prior cancers now in remission for 3 years or longer
• Direct tumor extension into the stomach, duodenum * NOTE: Tumor abutment of stomach or duodenum will be acceptable, per PI discretion
• Severe active co-morbidities, at the discretion of the principal investigator
• All participants: Participants should not donate blood or blood components while participating in this study and through 180 days after the last study dose
• Major surgery (e.g., gastrointestinal (GI) surgery, removal or biopsy of brain metastasis) within 8 weeks before SBRT. Complete wound healing from major surgery should have occurred 1 month before SBRT. Healing from minor surgery (eg, simple excision, tooth extraction) at least 10 days before SBRT. Patients with clinically relevant ongoing complications from prior surgery are not eligible
• Uncontrollable ascites or pleural effusion
• Abdominal fistula, GI perforation, bowel obstruction, or intra-abdominal abscess within 8 weeks before first dose. Note: Complete healing of an intra-abdominal abscess must be confirmed before SBRT
• History of active autoimmune disease (active defined as having autoimmune disease related symptoms and detectable autoantibodies) that has required systemic treatment
• Diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to SBRT. Except Intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra articular injection). Systemic corticosteroids are acceptable if in treatment of immunotherapy-related toxicity or steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication) are also acceptable
• Clinically significant gross hematuria, hematemesis, or hemoptysis of > 0.5 tsp (2.5ml) of red blood, or other history of grade 3 significant bleeding
• Cholangiocarcinoma (intra/extra-hepatic)