Stereotactic Radiation Therapy in Treating Patients With Advanced Liver Cancer

Study Overview
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Brief Summary
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RATIONALE: Stereotactic radiation therapy may be able to send x-rays directly to the tumor and cause less damage to normal tissue. PURPOSE: This phase I trial is studying the side effects and best dose of stereotactic radiation therapy in treating patients with advanced liver cancer.

Detailed Description
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OBJECTIVES: Primary To determine the safety of hypofractionated stereotactic radiotherapy (SRT) in patients with advanced hepatocellular carcinoma. Secondary To determine the maximum tolerated dose of SRT in these patients. To determine the objective tumor response rate in terms of the percentage of tumor size change on CT, percentage of intensity change on MRI, and the percentage of change in alfa fetoprotein in patients treated with this therapy. To determine the value of 4-dimensional CT in liver cancer planning in terms of the extent of liver motion (three dimensionally) and the percentage of patients requiring breath gating due to the amplitude of organ motion exceeding 1 cm in any dimension. To determine the value of breath gating in liver cancer SRT in terms of the success rate of breath gating and the percentage of treatment time prolongation secondary to the gating. OUTLINE: Patients undergo hypofractionated stereotactic radiotherapy once daily on days 1-5. After completion of study therapy, patients are followed at 1 and 3 months.

Official Title
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Feasibility of Hypofractionated Stereotactic Radiotherapy in Patients With Hepatocellular Carcinoma

Conditions
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Liver Cancer

Intervention / Treatment
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* Radiation: stereotactic body radiation therapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically or cytologically confirmed advanced hepatocellular carcinoma (HCC) Measurable disease, defined as ≥ 1 unidimensionally target lesion that can be accurately measured by CT scan or MRI according to RECIST and must have a maximum diameter ≤ 8 cm Child-Pugh class A-B cirrhotic status Karnofsky performance status 60-100% Life expectancy ≥ 12 weeksWBC ≥ 2,000/μL Platelet count ≥ 60,000/mm³ Hemoglobin ≥ 8.5 g/dLINR ≤ 2.3 More than 6 months since prior myocardial infarction Prior systemic chemotherapy allowed At least 6 weeks since prior non-radiation local therapy (e.g., surgery, hepatic arterial therapy, chemoembolization, radiofrequency ablation, percutaneous ethanol injection, or cryoablation) Concurrent therapeutic anticoagulation (e.g., warfarin or heparin) allowed provided that no prior evidence of underlying abnormality in PT, PTT, INR exists Exclusion Criteria: No known CNS tumors, including metastatic brain disease No malignancy within the past 3 years that is distinct in its primary site or histology from HCC, except for carcinoma in situ of the cervix, treated basal cell carcinoma, or superficial bladder tumors (i.e., Ta, Tis, and T1), or any other cancer that has been curatively treated > 3 years prior to study entry No renal failure requiring hemodialysis or peritoneal dialysis No uncontrolled intercurrent illness including, but not limited to, any of the following: Ongoing or active infection > grade 2 NYHA class II-IV congestive heart failure Active coronary artery disease Cardiac arrhythmias requiring anti-arrhythmic therapy other than beta blockers or digoxin Uncontrolled hypertension Condition that could jeopardize the safety of the patient or study compliance No history of variceal bleeding where the varices have not been eradicated or decompressed by shunt placement No condition that would prevent the patient from undergoing marker implantation Not pregnant or nursing/negative pregnancy test No substance abuse, medical, psychological, or social condition that may interfere with the patient's participation in the study or evaluation of the study results No prior radiotherapy to the liver

Ages Eligible for Study
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Minimum Age: 19 Years
Maximum Age: 120 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: Hypofractionated stereotactic radiotherapy (SRT)<br>All patients who have had successful implantation of a liver marker will undergo a 4D CT scan for planning SRT. Following transfer to the treatment planning system, the CT scan may be correlated by imaging fusion with MRI for contouring integrated tumor volume (ITV). The planning target volume (PTV) will be defined as ITV plus individualized margins which are determined by a 4D CT scan. Novalis with 6MV photons will be used for imaging guided SRT. Cohorts of 3-6 patients will receive SRT at daily doses of 8, 10, 12, 14 Gy within 2 weeks. The starting daily dose level will be 10 Gy. The marker will be localized by orthogonal X-ray to ensure reproducibility. A continuous respiratory gating will be accomplished with ExacTrac Adaptive Gating system if the required planning target margin is larger than 1 cm based on the 4D CT data. | Radiation: stereotactic body radiation therapy<br>* Undergo radiotherapy<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Toxicity as assessed by NCI CTCAE v3.0 | Toxicity as assessed by NCI CTCAE v3.0 | Up to 1 month after SRT | 
| Maximum tolerated dose | Maximum tolerated dose | At least 1 month of observation after surgery | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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adult primary hepatocellular carcinoma, advanced adult primary liver cancer, localized unresectable adult primary liver cancer, recurrent adult primary liver cancer