Proton Therapy in the Treatment of Liver Metastases

Study Overview
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Brief Summary
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Local control of hepatic metastases appears to be a major determinant of overall survival. However, many patients are not suitable for resection due to medical or surgical reasons. Therefore, there is an important role for a treatment that can provide the equivalent of tumor resection with minimal morbidity. Stereotactic body radiotherapy (SBRT) delivers an ablative regimen of highly focused external beam radiotherapy that targets one or more discrete extracranial lesions. Published reports using SBRT to treat liver metastases have shown actuarial local control rates ranging from 50-100% with higher doses associated with better local control. In patients with metastatic liver disease, aggressive local therapy using modern radiotherapy techniques are promising and project to have a substantial role in the treatment of metastatic liver cancer to treat unresectable disease. The dosimetric advantage of proton therapy may lead to improved clinical outcomes with less morbidity, however, there is no clinical data to confirm this assertion. We thus propose a phase I study to determine the feasibility and safety of stereotactic body proton therapy in patients with liver metastases followed by a phase II study to determine the efficacy of such treatment on local control.

Official Title
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Phase I-II Trial of Stereotactic Body Proton Therapy for Patients With Liver Metastases

Conditions
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Liver Metastases

Intervention / Treatment
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* Radiation: Proton
* Radiation: Proton Radiation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Pathologically confirmed non-lymphoma liver metastases or New radiographic liver lesions consistent with metastases in patients with known pathologically confirmed non-lymphoma cancer 1-3 liver lesions measurable on CT/MRI or PET/CT performed within 6 weeks prior to study entry Liver metastases measuring <5cm Life expectancy >6 months Disease outside the liver is allowed Age ≥ 18 ECOG Performance Scale = 0-1 Adequate bone marrow function, defined as follows: Absolute neutrophil count (ANC) ≥ 1,000 cells/mm3 based upon CBC/differential obtained within 4 weeks prior to registration on study Platelets ≥ 60,000 cell/mm3 based upon CBC/differential obtained within 4 weeks prior to registration on study Hemoglobin ≥ 8.0 g/dl based upon CBC/differential obtained within 4 weeks prior to registration on study (Note: the use of transfusion or other intervention to achieve Hgb ≥ 8.0 is acceptable.) Adequate kidney function (serum creatinine <2mg/dL) based on chemistry panel obtained within 4 weeks prior to registration on study Adequate liver function, defined as total bilirubin <5 mg/dL, serum albumin >2.0g/dL, serum levels of liver enzymes < 5 times the upper limit of normal, and INR < 1.5 Previous liver resection or ablative therapy is permitted Chemotherapy and/or targeted agent therapy must be completed at least 2 weeks prior to radiation and started at least 14 days after completion of SBPT Women of childbearing potential and male participants must practice adequate contraception Patient must sign study specific informed consent prior to study entry Pretreatment evaluations required for eligibility include: A complete history and general physical examination For women of childbearing potential, a serum or urine pregnancy test must be performed within 72 hours prior to registration INR, total bilirubin, albumin, alkaline phosphatase, ALT, AST within 4 weeks prior to study entry Exclusion Criteria: Prior invasive malignancy other than liver met primary (except non-melanomatous skin cancer) unless disease free for > 3years Prior radiotherapy that would results in overlap of radiation fields Prior radiotherapy to the liver Severe, active co-morbidity that may impact survival CNS metastases Tense ascites requiring frequent paracentesis Active liver infection Pregnancy, nursing women, or women of child bearing potential, and men who are sexually active and not willing/able to use medically acceptable forms of contraception Metastases location within 2cm of GI tract -

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: Proton Radiation<br> | Radiation: Proton<br>* All patients will receive 3 fractions in no more than 14 days at the following levels: Level I = 12 Gy per fraction, total dose=36 Gy. Level II = 16 Gy per fraction, total dose 48 Gy. Level III = 20 Gy per fraction, total dose 60 Gy. The dose per fraction to the PTV will start at dose level I (12 Gy), but may vary from 12 Gy to 20 Gy in 3 fractions over 14 days in 4 Gy increments<br>Radiation: Proton Radiation<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phase I of study: Number of participants with adverse events as a measure of safety and tolerability |  | The major analysis for reporting the initial results of treatment will be undertaken when each patient has been potentially followed for a minimum of 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phase II -local control within irradiated fields at 2 years |  | The major analysis for reporting the initial results of treatment will be undertaken when each patient has been potentially followed for a minimum of 3 months |