Stereotactic Body Radiation Therapy in Treating Patients With Liver Cancer

Study Overview
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Brief Summary
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This trial studies how well stereotactic body radiation therapy works in treating patients with liver cancer. Stereotactic body radiation therapy uses special equipment to position a patient and deliver radiation to tumors with high precision. This method can kill tumor cells with fewer doses over a shorter period and cause less damage to normal tissue.

Detailed Description
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PRIMARY OBJECTIVE: I. Assess the use of stereotactic body radiation therapy (SBRT) in hepatocellular carcinoma (HCC) patients with advanced liver cirrhosis as a feasible approach to providing localized disease control that adequately suffices liver transplant eligibility criteria. SECONDARY OBJECTIVE: I. Assess preliminary efficacy and toxicity in HCC patients with advanced cirrhosis following liver SBRT. EXPLORATORY OBJECTIVE: I. Assess qualify of life in HCC patients with advanced cirrhosis following liver SBRT. OUTLINE: Patients undergo SBRT on days 1, 3, 5, 7, and 9 in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up at 6 weeks, then every 3 months for up to 2 years.

Official Title
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A Pilot Study to Assess Feasibility of Hypofractionation and Stereotactic Body Radiation Therapy for Hepatocellular Carcinoma Patients Awaiting Liver Transplantation

Conditions
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Hepatocellular Carcinoma

Intervention / Treatment
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* Other: Quality-of-Life Assessment
* Other: Questionnaire Administration
* Radiation: Stereotactic Body Radiation Therapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Ability to understand and the willingness to sign a written informed consent document Must be listed or recommended to be listed for orthotopic liver transplantation at the participating institution Have a Child-Pugh (CP) score >= B8 Eastern Clinical Oncology Group (ECOG) performance status =< 2, or Karnofsky performance scale > 60 Must have a life expectancy > 12 weeks Safe radiation treatment planning parameters that adhere to all organs at risk constraints per section 5.1 of the protocol. If normal organs at risk constraints (including at least 700cc of uninvolved liver) are unable to be met at the lowest dose modification (30 Gy in 5 fractions), the patient is deemed ineligible for SBRT and deemed a screen failure Except for prior radiotherapy or radioembolization, other prior therapies to previously treated lesions, are permitted People of childbearing potential must have a negative urine or serum pregnancy test within 72 hours prior to receiving the first dose of SBRT. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required Participants of childbearing potential are those who have not been surgically sterilized or have not been free from menses for > 1 year without an alternative medical cause Note: Abstinence is acceptable if this is the preferred contraception for the participant No other prior invasive malignancy is allowed except for the following: adequately treated basal (or squamous cell) skin cancer, in situ breast or cervical cancer. Stage I or II invasive cancer treated with a curative intent without evidence of disease recurrence for at least five years Exclusion Criteria: Participants have any one of the following liver tumor characteristics: Have > 5 liver tumors, or Maximal diameter > 5 cm Complete obstruction of portal venous flow to the segment of liver that includes the target lesion Prior radiotherapy to the upper abdomen or radioembolization of the liver, or prior thermal ablation to the target lesion For fiducial marker placement: Have a gold allergy Any coagulopathy preventing safe fiducial placement Contraindication to both contrast enhanced magnetic resonance imaging (MRI) and contrast enhanced computed tomography (CT) (i.e. unable to undergo follow-up imaging or SBRT treatment planning) Participation in another concurrent treatment protocol Participant is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the screening visit through 120 days after the last dose of trial treatment Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, interstitial lung disease, serious chronic gastrointestinal conditions associated with diarrhea, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring adverse events (AEs) or compromise the ability of the patient to give written informed consent

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: Treatment (SBRT)<br>Patients undergo SBRT on days 1, 3, 5, 7, and 9 in the absence of disease progression or unacceptable toxicity. | Other: Quality-of-Life Assessment<br>* Ancillary studies<br>* Other names: Quality of Life Assessment;Other: Questionnaire Administration<br>* Ancillary studies<br>Radiation: Stereotactic Body Radiation Therapy<br>* Undergo SBRT<br>* Other names: Stereotactic Ablative Body Radiation Therapy;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of participants who are transplanted or with localized disease control per Milan criteria | Will be reported with 95% exact confidence interval (CI). | Up to time of progression, or transplantation, or 1 year after last stereotactic body radiation therapy (SBRT) dose, whichever occurs first | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of progressive disease within or at the planned tumor volume (PTV) margin | The estimate of local control rate will be plotted using Kaplan-Meier curve and reported with median survival and 95% CI if available. | Up to time of progression, transplantation, death or 2 years after last SBRT dose, whichever occurs first | 
| Incidence of intrahepatic progressive disease | Will be plotted using Kaplan-Meier curve and reported with median survival and 95% CI if available. | Up to time of progression, transplantation, death or 2-years after last SBRT dose, whichever occurs first | 
| Incidence of extrahepatic progressive disease |  | Up to time of progression, transplantation, death or 2-years after last SBRT dose, whichever occurs first | 
| Proportion of participants that proceed to transplantation | Will be measured and reported with 95% CI. | Up to time of progression, transplantation, death or 2-years after last SBRT dose, whichever occurs first | 
| Overall survival | Will be plotted using Kaplan-Meier curve and reported with median survival and 95% CI if available. | Up to time of death or 2 years after last SBRT dose | 
| Incidence of non-classic radiation-induced liver disease (RILD) defined as grade 4 aspartate aminotransferase or alanine aminotransferase elevation, or an increase in Child Pugh (CP) score of >= 2 within 1 week to 3 months after completing SBRT | Will be estimated along with an exact CI using the safety analysis set. | Up to 3 months after last SBRT dose | 
| Incidence of liver toxicity assessed per Common Terminology Criteria for Adverse Events (CTCAE) version (v) 5.0 | Will be estimated along with an exact CI using the safety analysis set. | Within 1 week to 3 months after completing SBRT |