Stereotactic Radiation Therapy in Treating Patients With Liver Metastases

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/II trial is studying the side effects and best dose of stereotactic radiation therapy in treating patients with liver metastases.

Detailed Description
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OUTLINE: This is a phase I/II, dose-escalation study. Phase I: Patients undergo either percutaneous placement of metallic fiducial markers within the liver or respiratory-correlated cone-beam computed tomography for stereotactic targeting and planning. Patients then undergo single-fraction stereotactic body radiotherapy over approximately 1 hour within 1 week of the marker placement. Phase II: Patients undergo treatment as in phase I at the maximum tolerated dose. After completion of study treatment, patients will be followed at weeks 4 and 12 and then every 3 months for 2 years. PROJECTED ACCRUAL: A total of 60 patients will be accrued for this study.

Official Title
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A Phase I/II Dose-Finding Study of Single-Fraction Stereotactic Body Radiotherapy (SF-SBRT) for the Treatment of Liver Metastases

Conditions
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Unspecified Adult Solid Tumor

Intervention / Treatment
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* Radiation: stereotactic radiation therapy
* Procedure: implanted fiducial-based imaging
* Procedure: cone-beam computed tomography


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histological confirmation (any histology except lymphoma, leukemia, or hepatocellular carcinoma) of at least one liver lesion that is synchronous to the primary diagnosis of malignancy or metachronous as a recurrence/metastasis or as a failure following previous therapy (except radiotherapy). One to three metastatic liver lesions =< 5 cm in dimension. Intrahepatic cholangiocarcinoma is acceptable for inclusion. Zubrod Performance Status (PS) 0 or 1. Please contact study investigator and/or consult protocol document for specific details on laboratory criteria. Life expectancy >= 12 weeks. MELD (Model for End-Stage Liver Disease) score =< 16. >= 1000 cc of uninvolved liver parenchyma as determined by the treating physician. Determination that the patient is medically inoperable and/or unwilling to undergo liver resection in patients with colorectal carcinoma histology. Provide informed written consent. Willingness to return to Mayo Clinic Rochester for follow-up. Exclusion Criteria: Pregnant women. Nursing women. Men or women of childbearing potential or their partners who are unwilling to employ adequate contraception. Co-morbid systemic illnesses or other severe concurrent disease, defined as those which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens Immunocompromised patients (other than that related to the use of corticosteroids) including patients known to be HIV positive. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements. Receiving any other investigational agent which would be considered as a treatment for the primary neoplasm =< 7 days prior to registration. Administration of chemotherapy within 2 wks prior to or 2 wks following SF-SBRT. Prior radiation therapy to the liver Untreated malignant biliary obstruction (patients treated successfully with stenting are eligible). Current diagnosis of hepatocellular carcinoma

Ages Eligible for Study
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Minimum Age: 18 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: Arm I<br>Patients undergo either percutaneous placement of metallic fiducial markers within the liver or respiratory-correlated cone-beam computed tomography for stereotactic targeting and planning. Patients then undergo single-fraction stereotactic body radiotherapy over approximately 1 hour within 1 week of the marker placement. | Radiation: stereotactic radiation therapy<br>* Patients undergo stereotactic body radiation therapy<br>Procedure: implanted fiducial-based imaging<br>* radiation therapy treatment planning<br>Procedure: cone-beam computed tomography<br>* radiation therapy treatment planning<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determination of the Maximum Tolerated Dose (MTD) of Single-fraction Stereotactic Body Radiation Therapy (SF-SBRT) in Hepatic Metastases. |  | 2 months | 
| Determine the Minimum Effective Dose (MED) Necessary for Durable Local Control, Defined as the Dose Level at Which Local Control (LC) is >= 80% at 1 Year. (Phase II) | LC is defined as no evidence of disease progression within the volume treated to prescription dose (i.e. PTV) for a specific lesion. The development of new intrahepatic metastases sites outside of the PTV will not be considered local failures. | At 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Toxicity and Adverse Events Profile (Phase I) | Number of patients with a grade >= 3 adverse event. Adverse events were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 3. Description of Grades: Grade 1: Mild Grade 2: Moderate Grade 3: Severe Grade 4: Life-threatening Grade 5: Death | Up to 2 years | 
| Patient Clinical Response and Treatment Effects on Blood Chemistry and Hepatic Function Markers (Phase I) |  | Up to 2 years | 
| Radiographic Response Rate (Phase II) |  | Up to 2 years | 
| Local Control (LC) Cumulative Incidence Rates (Phase II) |  | 3 and 6 months and 1, 2, and 5 years | 
| Median Time to Progression of Treated Tumors (Phase II) |  | Up to 5 years | 
| Refinement of Toxicity and Adverse Events Profile (Phase II) |  | Up to 2 years | 
| Refinement of Patient Clinical Response and Treatment Effects on Blood Chemistry and Hepatic Function Markers (Phase II) |  | Up to 2 years | 
| Evaluation of Cause of Death (Phase II) |  | Up to 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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protocol specific