Hepatocellular Carcinoma (HCC)
Conditions
Brief summary
The proposed study is a single site, prospective, randomized pilot study to assess the feasibility of recruitment of patients into a trial evaluating the efficacy and tolerability of selective transarterial Y90 radioembolization (radiation segmentectomy) versus stereotactic body radiation therapy (SBRT) for solitary early stage (≤ 3cm) hepatocellular carcinoma (HCC).
Interventions
RADIATIONYttrium-90 Radiation Segmentectomy
This therapy arm involves two separate steps, a planning/mapping arteriogram and a therapy delivery. The planning arteriogram will be performed to confirm arterial anatomy is acceptable for RS (≤2 segment delivery) and that lung shunting is not too high to preclude treatment with RS. Once confirmed, patients will return for RS (within 45 days of mapping). Dose will be calculated based off the desired treatment volume using pre-treatment cross-sectional imaging. The desired segmental dose will be calculated to be ≥ 200Gy. RS will be performed by one of three separate interventional radiologists with experience in radioembolization. Actual administered activity and location of dose administration will be recorded.
RADIATIONStereotactic Body Radiation Therapy
SBRT will be delivered with linear accelerator-based photon beams with either fixed angle non- coplanar fields or dynamic arcs. An internal target volume (ITV) will be generated to account for tumor movement during breathing cycle. Finally, a planning target volume (PTV) will be an expansion of 3- 5mm from the ITV. For Child Pugh A patients, prescription dose will either be 5000cGy in 5 fractions delivered every other day or 4800cGy in 3 fractions delivered twice weekly. For Child Pugh B patients, prescription dose of 4000cGy in 5 fractions delivered every other day. Inverse planning will be used. 95% of the PTV or more will receive at least 100% of the prescription dose. Normal tissue dose constraints for each dose level will be respected with acceptable deviations permitted as outlined in appendix VII. Patients will be seen at least once per week by a clinician to grade toxicities, with on- treatment labs (CBC, CMP, INR) each week.
Sponsors
Indiana University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Masking description
Radiologist assessing response will be blinded to the treatment type
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Ability to provide written informed consent and HIPAA authorization * Stated willingness to comply with all study procedures and availability for the duration of the study * Male or female, aged ≥ 18 years at time of informed consent * Solitary HCC (≤3 cm) diagnosed by imaging (LI-RADS 4-5) or histology * Childs-Pugh score ≤ 7 * ECOG performance status 0-1 * Tumor location/characteristics eligible for either SBRT or Y90 therapy as deemed by local tumor board * Adequate organ function defined as: 1. serum bilirubin \< 4.0 mg/dL , 2. albumin \> 2 g/dL
Exclusion criteria
* Any prior locoregional therapy to the target tumor * Any prior radiation therapy to the liver * Pregnancy or lactation: Women of childbearing potential must have a negative pregnancy test within 14 days of protocol registration. Women are considered to have childbearing potential (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) unless they meet one of the following criteria: i. Has undergone a hysterectomy or bilateral oophorectomy; or ii. Has been naturally amenorrheic for at least 24 consecutive months * Known severe allergic reaction (anaphylaxis) to iodinated contrast * Coagulopathy (platelets \< 50 K/mm3 and/or INR \> 2) not correctable by transfusion * Macrovascular invasion or extrahepatic HCC
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Feasibility of Recruitment (Recruitment Rate) | 24 months | Feasibility of recruitment will be measured by evaluating the proportion of patients enrolled versus those approached for the study after they have been determined to be a candidate. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change in Hepatobiliary Function | 16 months for the first subject and 4 months for the second | the mean change in hepatobiliary function, as measured 3 months after treatment using a functional HIDA scan, between RS and SBRT for patients with small (≤3 cm) solitary hepatocellular carcinoma (HCC). |
| Mean Change in Functional Assessment of Cancer Therapy- General (FACT-G) Score | 6 months | the mean change in patient-reported outcomes from baseline, at 1, 3 and 6 months, between RS and SBRT, for patients with small (≤3 cm) solitary hepatocellular carcinoma (HCC), using the Functional Assessment of Cancer Therapy- General (FACT-G). scale goes from 0-108 with a higher score being better. |
| Mean Change in Comprehensive Score for Financial Toxicity | 6 months | the mean change in patient-reported outcomes from baseline, at 1, 3 and 6 months, between RS and SBRT, for patients with small (≤3 cm) solitary hepatocellular carcinoma (HCC), using the Comprehensive Score for Financial Toxicity (COST). scale is from 0-44 with higher being bettter |
| Proportion of Patients With Any Toxicities | 16 months for the first subject and 4 months for the second | the proportion of patients with any toxicities (≥ grade 4) using CTCAE between RS and SBRT for patients with small (≤3 cm) solitary hepatocellular carcinoma (HCC). |
| Time-to-secondary Treatment (TTST) Between RS and SBRT | 16 months for the first subject and 4 months for the second | time-to-secondary treatment (TTST) between RS and SBRT for patients with small (≤3 cm) solitary hepatocellular carcinoma (HCC) up to 2 years after initial treatment. |
| Objective Response Rate | 6 months | the objective response rate (ORR) of radiation segmentectomy (RS) and stereotactic body radiation therapy (SBRT) as measured at 6 months using mRECIST (appendix IV) for patients with small (≤3 cm) solitary hepatocellular carcinoma (HCC) to better allow for an appropriately powered trial evaluating the efficacy of these treatments. |
| Disease-free Survival (DFS) Rates of RS and SBRT | 16 months for the first subject and 4 months for the second | the disease-free survival (DFS) rates of RS and SBRT at 2 years using mRECIST on CT or MR for patients with small (≤3 cm) solitary hepatocellular carcinoma (HCC). |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Yttrium-90 Radiation Segmentectomy Yttrium-90 Radiation Segmentectomy: This therapy arm involves two separate steps, a planning/mapping arteriogram and a therapy delivery. The planning arteriogram will be performed to confirm arterial anatomy is acceptable for RS (≤2 segment delivery) and that lung shunting is not too high to preclude treatment with RS. Once confirmed, patients will return for RS (within 45 days of mapping). Dose will be calculated based off the desired treatment volume using pre-treatment cross-sectional imaging. The desired segmental dose will be calculated to be ≥ 200Gy. RS will be performed by one of three separate interventional radiologists with experience in radioembolization. Actual administered activity and location of dose administration will be recorded. | 1 |
| Stereotactic Body Radiation Therapy Stereotactic Body Radiation Therapy: SBRT will be delivered with linear accelerator-based photon beams with either fixed angle non- coplanar fields or dynamic arcs. An internal target volume (ITV) will be generated to account for tumor movement during breathing cycle. Finally, a planning target volume (PTV) will be an expansion of 3- 5mm from the ITV. For Child Pugh A patients, prescription dose will either be 5000cGy in 5 fractions delivered every other day or 4800cGy in 3 fractions delivered twice weekly. For Child Pugh B patients, prescription dose of 4000cGy in 5 fractions delivered every other day. Inverse planning will be used. 95% of the PTV or more will receive at least 100% of the prescription dose. Normal tissue dose constraints for each dose level will be respected with acceptable deviations permitted as outlined in appendix VII. Patients will be seen at least once per week by a clinician to grade toxicities, with on- treatment labs (CBC, CMP, INR) each week. | 1 |
| Total | 2 |
Baseline characteristics
| Characteristic | Yttrium-90 Radiation Segmentectomy | Stereotactic Body Radiation Therapy | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 1 Participants | 1 Participants |
| Age, Categorical Between 18 and 65 years | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 1 Participants | 1 Participants | 2 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 1 Participants | 1 Participants | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 1 | 0 / 1 |
| other Total, other adverse events | 1 / 1 | 1 / 1 |
| serious Total, serious adverse events | 0 / 1 | 0 / 1 |
Outcome results
Primary
Feasibility of Recruitment (Recruitment Rate)
Feasibility of recruitment will be measured by evaluating the proportion of patients enrolled versus those approached for the study after they have been determined to be a candidate.
Time frame: 24 months
Population: This group consists of all patients who fit inclusion/exclusion criteria and were approached for enrollment in the study
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Eligible Participants | Feasibility of Recruitment (Recruitment Rate) | recruited | 2 Participants |
| Eligible Participants | Feasibility of Recruitment (Recruitment Rate) | declined to participate | 20 Participants |
Secondary
Disease-free Survival (DFS) Rates of RS and SBRT
the disease-free survival (DFS) rates of RS and SBRT at 2 years using mRECIST on CT or MR for patients with small (≤3 cm) solitary hepatocellular carcinoma (HCC).
Time frame: 16 months for the first subject and 4 months for the second
Population: No data were collected for this outcome measure because 0 participants remained enrolled in this time frame
Secondary
Mean Change in Comprehensive Score for Financial Toxicity
the mean change in patient-reported outcomes from baseline, at 1, 3 and 6 months, between RS and SBRT, for patients with small (≤3 cm) solitary hepatocellular carcinoma (HCC), using the Comprehensive Score for Financial Toxicity (COST). scale is from 0-44 with higher being bettter
Time frame: 6 months
Population: data collected for single y90 pt. data not collected for SBRT pt
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Eligible Participants | Mean Change in Comprehensive Score for Financial Toxicity | baseline | 27 score on a scale |
| Eligible Participants | Mean Change in Comprehensive Score for Financial Toxicity | 1 month | 29 score on a scale |
| Eligible Participants | Mean Change in Comprehensive Score for Financial Toxicity | 3 month | 23 score on a scale |
| Eligible Participants | Mean Change in Comprehensive Score for Financial Toxicity | 6 month | 16 score on a scale |
Secondary
Mean Change in Functional Assessment of Cancer Therapy- General (FACT-G) Score
the mean change in patient-reported outcomes from baseline, at 1, 3 and 6 months, between RS and SBRT, for patients with small (≤3 cm) solitary hepatocellular carcinoma (HCC), using the Functional Assessment of Cancer Therapy- General (FACT-G). scale goes from 0-108 with a higher score being better.
Time frame: 6 months
Population: for single Y90 pt data was collected. Data not collected for SBRT pt.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Eligible Participants | Mean Change in Functional Assessment of Cancer Therapy- General (FACT-G) Score | 3 month | 82 score on a scale |
| Eligible Participants | Mean Change in Functional Assessment of Cancer Therapy- General (FACT-G) Score | 6 month | 78 score on a scale |
| Eligible Participants | Mean Change in Functional Assessment of Cancer Therapy- General (FACT-G) Score | base line score | 69 score on a scale |
| Eligible Participants | Mean Change in Functional Assessment of Cancer Therapy- General (FACT-G) Score | 1 month | 75 score on a scale |
Secondary
Mean Change in Hepatobiliary Function
the mean change in hepatobiliary function, as measured 3 months after treatment using a functional HIDA scan, between RS and SBRT for patients with small (≤3 cm) solitary hepatocellular carcinoma (HCC).
Time frame: 16 months for the first subject and 4 months for the second
Population: 1 pt in y90 arm had 3 month scan to compare to baseline. no other scans
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Eligible Participants | Mean Change in Hepatobiliary Function | 9.1 percentage of liver function decrease |
Secondary
Objective Response Rate
the objective response rate (ORR) of radiation segmentectomy (RS) and stereotactic body radiation therapy (SBRT) as measured at 6 months using mRECIST (appendix IV) for patients with small (≤3 cm) solitary hepatocellular carcinoma (HCC) to better allow for an appropriately powered trial evaluating the efficacy of these treatments.
Time frame: 6 months
Population: No data were collected for this outcome measure because 0 participants in the SBRT arm remained enrolled in this time frame and 6 month imaging was unavailable for the pt in the y90 arm
Secondary
Proportion of Patients With Any Toxicities
the proportion of patients with any toxicities (≥ grade 4) using CTCAE between RS and SBRT for patients with small (≤3 cm) solitary hepatocellular carcinoma (HCC).
Time frame: 16 months for the first subject and 4 months for the second
Population: No data were collected for this outcome measure because 0 participants remained enrolled in this time frame
Secondary
Time-to-secondary Treatment (TTST) Between RS and SBRT
time-to-secondary treatment (TTST) between RS and SBRT for patients with small (≤3 cm) solitary hepatocellular carcinoma (HCC) up to 2 years after initial treatment.
Time frame: 16 months for the first subject and 4 months for the second
Population: No data were collected for this outcome measure because 0 participants remained enrolled in this time frame