Hepatocellular Carcinoma
Conditions
Brief summary
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
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.
Interventions
OTHERQuality-of-Life Assessment
Ancillary studies
OTHERQuestionnaire Administration
Ancillary studies
RADIATIONStereotactic Body Radiation Therapy
Undergo SBRT
Sponsors
Radiation Oncology Institute
Oregon Health and Science University
OHSU Knight Cancer Institute
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Participants Who Are Transplant Eligible 1 Year Following SBRT | From first SBRT dose to time of disease progression, transplantation, or 1 year after last SBRT dose (Day 374), whichever occurs first | Transplant eligible means transplanted within 1 year or having localized disease control that meets Milan criteria at 1-year post-SBRT. Reported with 95% exact confidence interval. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Extrahepatic Progressive Disease | From first dose of SBRT to time of extrahepatic disease progression, transplantation, death, or 2 years after last SBRT dose (Day 739), whichever occurs first. | Extrahepatic progressive disease is defined as progressive disease outside of the liver. |
| Overall Survival | From first SBRT dose to time of death or 2 years after last SBRT dose (Day 739), whichever occurs first. | Reported with median survival and 95% confidence interval, if available. |
| Incidence of Non-classic Radiation-induced Liver Disease (RILD) | From first SBRT dose to 3 months after last SBRT dose (Day 100) | Non-classic RILD is defined as grade 4 aspartate aminotransferase or alanine aminotransferase elevation, or an increase in Child-Pugh score of ≥ 2 within 1 week to 3 months after completing SBRT. Will be estimated along with an exact confidence interval. |
| Incidence of Liver Toxicity Within 1 Week to 3 Months After SBRT. | From 1 week (Day 16) to 3 months (Day 100) after completing SBRT | Liver toxicity is assessed per Common Terminology Criteria for Adverse Events (CTCAE) version (v) 5.0. Will be estimated along with an exact confidence interval. |
| Localized Control Rate | From first SBRT dose to time of disease progression, transplantation, death, or 2 years after last SBRT dose (Day 739), whichever occurs first | Local control is defined as the absence of progressive disease within or at the planning target volume (PTV) margin. |
| Incidence of Intrahepatic Progressive Disease | From first SBRT dose to time of intrahepatic disease progression, transplantation, death, or 2 years after last SBRT dose (Day 739), whichever occurs first. | Intrahepatic progressive disease is defined as development of intrahepatic recurrent or new disease within any section of the liver, including the PTV. |
| Proportion of Participants That Proceed to Transplantation | From first SBRT dose to time of disease progression, transplantation, death, or 2 years after last SBRT dose (Day 739), whichever occurs first. | Measured and reported with 95% confidence interval. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Proportion With Histopathologic Changes in Irradiated Tumor Sites Relative to Uninvolved Liver Tissue | At transplantation | Descriptive statistical analysis of the proportion of efficacy set participants with histopathologic changes in irradiated tumor sites (of explanted livers) relative to uninvolved liver tissue. |
| Quality of Life (QoL) Scores for European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-C30 Questionnaire | From screening to death or 2 years after last SBRT dose, whichever occurs first. | Summary of QoL over time. No hypothesis testing is planned for QoL. |
| QoL Scores for Functional Assessment of Cancer Therapy-Hepatobiliary (FACT-Hep) Questionnaire | From screening to death or 2 years after last SBRT dose, whichever occurs first. | Summary of QoL over time. No hypothesis testing is planned for QoL. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Treatment (SBRT) Patients undergo Stereotactic Body Radiation Therapy (SBRT), with 5 fractions planned for study days 1, 3, 5, 7, and 9, and a total dose of 40, 35, or 30 gray depending on normal organ constraints being met. | 9 |
| Total | 9 |
Baseline characteristics
| Characteristic | Treatment (SBRT) |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 3 Participants |
| Age, Categorical Between 18 and 65 years | 6 Participants |
| Age, Continuous | 58 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 7 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants |
| Race (NIH/OMB) White | 7 Participants |
| Region of Enrollment United States | 9 participants |
| Sex: Female, Male Female | 2 Participants |
| Sex: Female, Male Male | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 2 / 9 |
| other Total, other adverse events | 2 / 9 |
| serious Total, serious adverse events | 2 / 9 |
Outcome results
Primary
Proportion of Participants Who Are Transplant Eligible 1 Year Following SBRT
Transplant eligible means transplanted within 1 year or having localized disease control that meets Milan criteria at 1-year post-SBRT. Reported with 95% exact confidence interval.
Time frame: From first SBRT dose to time of disease progression, transplantation, or 1 year after last SBRT dose (Day 374), whichever occurs first
Population: Efficacy analysis set, comprising participants who have received at least 85% of the prescribed SBRT dose
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment (SBRT) | Proportion of Participants Who Are Transplant Eligible 1 Year Following SBRT | 66.7 percentage of participants |
Secondary
Incidence of Extrahepatic Progressive Disease
Extrahepatic progressive disease is defined as progressive disease outside of the liver.
Time frame: From first dose of SBRT to time of extrahepatic disease progression, transplantation, death, or 2 years after last SBRT dose (Day 739), whichever occurs first.
Population: Efficacy analysis set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment (SBRT) | Incidence of Extrahepatic Progressive Disease | 0.0 percentage of participants |
Secondary
Incidence of Intrahepatic Progressive Disease
Intrahepatic progressive disease is defined as development of intrahepatic recurrent or new disease within any section of the liver, including the PTV.
Time frame: From first SBRT dose to time of intrahepatic disease progression, transplantation, death, or 2 years after last SBRT dose (Day 739), whichever occurs first.
Population: Efficacy analysis set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment (SBRT) | Incidence of Intrahepatic Progressive Disease | 0.0 percentage of participants |
Secondary
Incidence of Liver Toxicity Within 1 Week to 3 Months After SBRT.
Liver toxicity is assessed per Common Terminology Criteria for Adverse Events (CTCAE) version (v) 5.0. Will be estimated along with an exact confidence interval.
Time frame: From 1 week (Day 16) to 3 months (Day 100) after completing SBRT
Population: Safety analysis set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment (SBRT) | Incidence of Liver Toxicity Within 1 Week to 3 Months After SBRT. | 11.1 percentage of participants |
Secondary
Incidence of Non-classic Radiation-induced Liver Disease (RILD)
Non-classic RILD is defined as grade 4 aspartate aminotransferase or alanine aminotransferase elevation, or an increase in Child-Pugh score of ≥ 2 within 1 week to 3 months after completing SBRT. Will be estimated along with an exact confidence interval.
Time frame: From first SBRT dose to 3 months after last SBRT dose (Day 100)
Population: Safety analysis set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment (SBRT) | Incidence of Non-classic Radiation-induced Liver Disease (RILD) | 0.0 percentage of participants |
Secondary
Localized Control Rate
Local control is defined as the absence of progressive disease within or at the planning target volume (PTV) margin.
Time frame: From first SBRT dose to time of disease progression, transplantation, death, or 2 years after last SBRT dose (Day 739), whichever occurs first
Population: Efficacy analysis set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment (SBRT) | Localized Control Rate | 100.0 percentage of participants |
Secondary
Overall Survival
Reported with median survival and 95% confidence interval, if available.
Time frame: From first SBRT dose to time of death or 2 years after last SBRT dose (Day 739), whichever occurs first.
Population: Efficacy analysis set
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Treatment (SBRT) | Overall Survival | 13.7 months |
Secondary
Proportion of Participants That Proceed to Transplantation
Measured and reported with 95% confidence interval.
Time frame: From first SBRT dose to time of disease progression, transplantation, death, or 2 years after last SBRT dose (Day 739), whichever occurs first.
Population: Efficacy analysis set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment (SBRT) | Proportion of Participants That Proceed to Transplantation | 66.7 percentage of participants |
Other Pre-specified
Proportion With Histopathologic Changes in Irradiated Tumor Sites Relative to Uninvolved Liver Tissue
Descriptive statistical analysis of the proportion of efficacy set participants with histopathologic changes in irradiated tumor sites (of explanted livers) relative to uninvolved liver tissue.
Time frame: At transplantation
Other Pre-specified
QoL Scores for Functional Assessment of Cancer Therapy-Hepatobiliary (FACT-Hep) Questionnaire
Summary of QoL over time. No hypothesis testing is planned for QoL.
Time frame: From screening to death or 2 years after last SBRT dose, whichever occurs first.
Other Pre-specified
Quality of Life (QoL) Scores for European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-C30 Questionnaire
Summary of QoL over time. No hypothesis testing is planned for QoL.
Time frame: From screening to death or 2 years after last SBRT dose, whichever occurs first.