Dose Escalation Study for Primary Hepatocellular Carcinoma

Study Overview
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Brief Summary
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The purpose of this study is to determine the maximum tolerated dose of limited fractions of large dose radiation in an effort to achieve a biologically potent cancer therapy in selected patients with primary hepatocellular carcinoma.

Detailed Description
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Despite recent advances in early detection and diagnosis, only 30-40% of patients with hepatocellular carcinoma may benefit from radical therapies. Liver transplantation offers the best chance for cure. Surgical resection has been the only other potentially curative option, but the majority of patients are not candidates for resection. This reflects the usual comorbidity of severe underlying liver disease that either precludes surgery or makes the surgical approach extremely dangerous.

Official Title
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Multi-institution Phase I/II Dose Escalation Study of Hypofractionated Stereotactic Body Radiation Therapy for Primary Hepatocellular Carcinoma

Conditions
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Carcinoma, Hepatocellular

Intervention / Treatment
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* Radiation: Stereotactic Body Radiation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Evaluation by the Surgery and/or Liver Transplant Team has been performed and the patient is not considered a candidate for either standard therapy to target area (upper abdomen) Adequate liver function defined as: total bilirubin < 3mg/dl, albumin > 2.5 g/dl normal PT/PTT unless on anticoagulants mild elevation of liver enzymes acceptable (must be less than three times upper limit of normal) Adequate renal function (creatinine < 1.8 mg/dl or creatinine clearance ≥ 50 ml/min) Adequate bone marrow reserve: ANC count ≥ 1500 mm3 Platelets ≥ 50,000/mm3 Hemoglobin > 9 g/dL NOTE: Lab values must be obtained within 2 weeks prior to being registered for protocol therapy. Exclusion Criteria: No history of systemic lupus erythematous, rheumatoid arthritis, systemic sclerosis or scleroderma No chemotherapy within 14 days before radiotherapy (chemotherapy may cause transient hepatitis with hepatomegaly) No subsequent chemotherapy planned within 2 weeks of radiotherapy No active liver infection No acute Hepatitis. Definition of active disease: Hepatitis A: Acute hepatitis determined by presence of Anti-HAV- IgM Hepatitis B: HBsAg (HB surface Antigen): present in patients with acute and chronic hepatitis HBV DNA present in patients with active viral replication in amounts greater than 100,000 copies HBeAg is present in wild type HBV infection and suggests active replication Anti-HBs: Antibody against HBsAg appears after HBV infections and confers immunity Anti-HBc-IgM: Antibody against HBcAg, fraction IgM, present in acute infection and often could be detected during periods of high viral replication in chronic disease Anti-HBc-IgG: is present in chronic disease

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Radiation Treatment Arm :A<br>Patients with a score of Childs A Will receive 3 fractions of radiation over 5-10 days | Radiation: Stereotactic Body Radiation<br>* Arm A: Childs A - receive 3 fractions. Arm B: Childs B - receive 5 fractions.<br>* Other names: Stereotactic Body Radiation Treatments;|
| Experimental: Radiation Treatment Arm: B<br>Patients with a score of Childs B will receive 5 fractions of radiation over 2-6 weeks. | Radiation: Stereotactic Body Radiation<br>* Arm A: Childs A - receive 3 fractions. Arm B: Childs B - receive 5 fractions.<br>* Other names: Stereotactic Body Radiation Treatments;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Patients With DLTs | Number of patients experiencing a Dose Limiting Toxicity during the Phase I portion of the trial. | 6 weeks | 
| 6 Month Local In-field Control | Percent of patients and the 95% Binomial Confidence interval who were free of in-field progression at 6 months following treatment for the patients in Phase II | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to In-field Failure | Kaplan-Meier Analyses will be used to calculate the median and 95% Confidence Interval for the time until in-field failure. This will be calculated from the time of treatment until the time of in-field failure. If a patient did not have in-field failure, the patient will be censored at their last evaluation date. | up to 4 yrs | 
| Overall Survival | Kaplan-Meier Analysis will be used to calculate the median and 95% CI for overall survival. This will be calculated from the time of treatment until death. If a patient did not die, the patient will be censored at their last known alive date. | Up to 8 years | 
| Phase II: Number of Patients With Treatment Related Grade 3 or 4 Adverse Events | Number of unique patients who had grade 3 or 4 adverse events that were possibly, probably or definitely related to study treatment. | up to 4 years |