vGRID SBRT: A Phase I Clinical Trial in Unresectable HCC

This trial will provide the maximum tolerated dose for radiation therapy for liver tumors and describe the toxicity profile using the vGRID therapy technique. Based on trials using this type of radiation in other cancers demonstrating low toxicity rates even with very high radiation doses and high efficacy, it is likely that vGRID therapy in this trial will be well tolerated and allow dose escalation beyond currently common doses for liver tumors.

Inclusion Criteria:Age ≥ 18 years oldUnresectable histologically confirmed hepatocellular carcinomaTotal Bilirubin < 3.0; Absolute Neutrophil Count > 1.5 K/UL without granulocyte colony- stimulating factor.Platelets > 70,000 cells/mm3;Hemoglobin > 8.0 g/dL (The use of transfusion to achieve Hg > 8.0g/dl is acceptable);INR or aPTT ≤ 2 x ULNAlbumin >2.9g/dl;AST and ALT < 6 times upper limit of normal (ULN); serum creatinine < 1.5x ULN or creatinine clearance > 60 mL/min.Stable anti-coagulation permitting: subcutaneous heparin acceptable.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 (see section with title CHILD-BEARING POTENTIAL / PREGNANCY).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.Negative HIV test at screening.Urine dipstick for proteinuria <2+ (within 7 days prior to initiation of study treatment) Patients discovered to have ≥ 2+proteinuria on dipstick urinalysis at baseline should undergo a 24-hour urine collection and must demonstrate < 1 g of protein in 24 hours.Documented virology status of hepatitis, as confirmed by screening HBV and HCV serology test.Esophageal Gastric Duodenoscopy (EGD) required within 45 days prior to enrollment to rule out uncontrolled esophageal varices.Exclusion Criteria:Prior abdominal radiation, including prior arterial Yttrium therapy.Is pregnant or breastfeedingDiagnosed with a psychiatric illness or is in a social situation that would limit compliance with study requirements.Patients being considered for transplant, with known fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiosarcinoma and HCC.Direct tumor extension into the stomach, duodenum, small bowel or large bowel .Cholangiocarcinoma (intra/extra-hepatic).Measurable common or main branch biliary duct involvement with tumor.Child Pugh Score 8 or higher.For patients with active hepatitis B virus (HBV): HBV DNA < 500 IU/mL obtained within 28 days prior to initiation of study treatment, and Anti-HBV treatment (per local standard of care; e.g., entecavir) for a minimum of 14 days prior to study entry and willingness to continue treatment for the length of the study.Hepatitis C treated according local guidelines.Severe active comorbidities, defined as follows:Unstable angina and/or congestive heart failure requiring. hospitalization within the last 6 months prior before registration.Transmural myocardial infarction within the last 6 months prior to study entry.Unstable ventricular arrhythmia within the last 6 months prior to study entry.Ongoing Infection > grade 2.Hepatic insufficiency resulting in clinical jaundice, encephalopathy and/or variceal bleed within 60 days prior to study entry.Thrombolytic therapy within 28 days prior to study entry. Subcutaneous heparin is permitted.Clinically significant gross hematuria, hematemesis, or hemoptysis of > 0.5 tsp (2.5ml) of red blood, or other history of grade 3 significant bleeding within 8 weeks.Known bleeding or clotting disorder.Uncontrolled psychotic disorder.Diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drugs. Except Intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra articular injection), Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or its equivalent, Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication).Active autoimmune disease (active defined as having autoimmune disease related symptoms and detectable autoantibodies) that has required systemic treatment in the past 2 years.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 first dose.Uncontrollable ascites or pleural effusion.Uncontrolled hypertension defined as sustained blood pressure (BP) > 150 mm Hg systolic or > 100 mm Hg diastolic despite optimal antihypertensive treatment.History of organ transplantation.Major surgery (e.g., GI surgery, removal or biopsy of brain metastasis) within 8 weeks before first dose of study treatment. Complete wound healing from major surgery must have occurred 1 month before first dose and from minor surgery (eg, simple excision, tooth extraction) at least 10 days before first dose. Patients with clinically relevant ongoing complications from prior surgery are not eligible.All participants: Participants should not donate blood or blood components while participating in this study and through 180 days after the last study dose.