A Pilot Study of Individualized Adaptive Radiation Therapy for Hepatocellular Carcinoma

Study Overview
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Brief Summary
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This is a pilot single arm study with the primary endpoints of feasibility and preliminary estimates of safety and efficacy. This protocol builds on over 25 years of experience with high dose liver RT (Radiation Therapy), and in particular adaptive RT aimed at adjusting the global radiation dose based on a patient's measured sensitivity to treatment. This current protocol uses functional imaging and specialized radiation planning techniques to spare highly functional portions of the liver to preserve function. The investigators feel this will further improve the safety and efficacy of RT for all patients by customizing treatments to each. If this approach is promising, the investigators will proceed to a phase II randomized study of standard versus spatially and dosimetrically adapted RT.

Official Title
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A Pilot Study of Individualized Adaptive Radiation Therapy for Hepatocellular Carcinoma

Conditions
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Hepatocellular Carcinoma

Intervention / Treatment
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* Radiation: Adaptive Radiation Therapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients must have hepatocellular carcinoma. Patients must not have extrahepatic cancer. Patients must not be eligible for a curative liver resection or have refused resection Patients must have recovered from the acute effects of prior liver-directed therapy and 4 weeks must have passed since the last procedure and protocol therapy. Patients must have a Zubrod performance status of less than or equal to 2 (Zubrod performance status is a measure that attempts to quantify a cancer patients' general well-being. Scores run from 0 to 5 where 0 denotes normal activity and 5 denotes death). Patients must be 18 years of age or older. Patients must have adequate organ function. Patients must understand and be willing to sign an IRB (Institutional Review Board) approved informed consent form. Exclusion Criteria: Patients with known allergies to intravenous iodinated contrast agents. Patients with a contraindication to contrast-enhanced MRI are excluded.

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Adaptive Radiation Therapy<br> | Radiation: Adaptive Radiation Therapy<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Proportion of Patients for Whom the Intended Treatment Was Feasible | The primary aim of the trial is feasibility which is defined as the ability to successfully deliver the full treatment including all adaptations and in particular the perfusion-based planning and replanning. | At end of treatment; up to  3 months | 
| Percentage of Patients With Change in Child Pugh Score >= 2 | Rate of liver decompensation reported as the percentage of patients with a change in Child Pugh score of greater than or equal to 2 within 6 months of SBRT. | Baseline to approximately 6 months after initiation of SBRT | 
| Median Time to Local Progression | The primary efficacy endpoint is local control, measured as the duration of time from start of treatment to time of progression of the treated (target) lesion(s). Patients with no evidence of local progression at the time of data analysis will be censored at the last date on which they were evaluated for local progression. Local progression will be summarized with Kaplan-Meier curves and reported with 95% confidence intervals. | 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Median Time to Progression | Defined as the duration of time from start of treatment to time of progression. | 24 months | 
| Change in ALBI Scores | Liver decompensation assessed by change in ALBI score > 0.5 from baseline. | Approximately 6 months | 
| Incidence of Grade 3 Gastrointestinal (GI) Bleeding Toxicities | Grade 3 GI bleeding assessed via the NCI CTCAE version 4.0. | Approximately 6 months | 
| Overall Survival | Overall survival (OS) is defined as the duration of time from start of treatment to death. | 24 months |