Hepatocellular Carcinoma, HCC
Conditions
Keywords
Hepatocellular Carcinoma (HCC), Liver transplant, Bridge to transplant, Stereotactic body radiation therapy (SBRT), Trans-arterial chemoembolization (TACE)
Brief summary
This study will compare stereotactic body radiation therapy (SBRT) to trans-arterial chemoembolization (TACE) as a bridging strategy for patients with HCC undergoing liver transplantation. We propose that SBRT will be associated with longer time intervals between initial treatment and the need for retreatment, compared to TACE, as a bridge to liver transplantation in subjects with HCC.
Detailed description
For patients with hepatocellular carcinoma (HCC) who are waiting for a liver transplant, local treatment of their disease has become the standard of care in an effort to decrease dropout rates and as a means of reducing tumor recurrence after transplantation. For patients undergoing local regional therapy as a bridge to transplantation, trans-arterial chemoembolization (TACE) is the most commonly utilized treatment. However, the best modality for patients undergoing treatment as a bridge to transplantation is unclear. A newer strategy for the treatment of HCC is stereotactic body radiation therapy (SBRT). This study will compare SBRT to TACE as a bridging strategy for patients with HCC undergoing liver transplantation.
Interventions
RADIATIONStereotactic Body Radiation Therapy (SBRT)
SBRT will be delivered in five total fractions, with at a minimum of one day between any two treatments. The entire treatment must be delivered within 15 total days.
First day will be administered and a second TACE will be administered after 4 weeks and subsequently if imaging is showing disease progression. Following each TACE procedure all patients will remain in hospital for observation
DRUGDoxorubin
This procedure will be completed with 2 vials of drug eluting beads each loaded with 50 mg of Doxorubin.
Sponsors
Varian Medical Systems
Merit Medical Systems, Inc.
Lahey Clinic
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Subjects with HCC are eligible for this trial. HCC is defined as having at least one of the following: * Biopsy proven HCC or: * A discrete hepatic tumor(s) as defined by the Barcelona (29) criteria for cirrhotic subjects, ≥2cm with arterial hypervascularity and venous or delayed phase washout on CT or MRI. 2. Subjects are liver transplant candidates (actively awaiting organ transplant per transplant services in documentation), or, potential liver transplant candidates (at the discretion of the liver team and/or Principal Investigator) advised by liver transplant services as needing local treatment prior to liver transplant evaluation. 3. Subjects must be within UCSF criteria (one solitary tumor smaller than 6.5 cm, or patients having 3 or fewer nodules, with the largest lesion being smaller than 4.5 cm or having a total tumor diameter less than 8.5 cm without vascular invasion) and eligible for potential liver transplant. 4. Subjects must be eligible per standard of care for either TACE or SBRT procedures. 5. Subjects must have a life expectancy of at least 12 weeks. 6. Subjects must be 18 years of age or older. Adult subjects of all ages, both sexes and all races will be included in this study. 7. Subjects must sign an informed consent form approved for this purpose by the Institutional Review Board (IRB) of record . 8. Subjects must have a Child-Turcotte-Pugh (CTP) score ≤8. 9. Patients must have adequate organ function within 2 weeks of enrollment. * Bone marrow: Platelets ≥30,000/mm3 * Renal: BUN ≤40 mg/dl; creatinine ≤2.0 mg/dl * Hepatic: INR ≤ 1.5 or correctable by Vitamin K, unless anti-coagulated for another medical reason * Bilirubin \< 3.0 mg/dl (in the absence of obstruction or pre-existing disease of the biliary tract, e.g. primary sclerosing cholangitis). 10. Patients uninvolved liver volume will be estimated and must be \> 700ml. 11. Patients must have a Zubrod performance status of ≤2.
Exclusion criteria
1. Subjects in a special category designated by the Public Health Service, Including subjects younger than 18, pregnant women, and prisoners. 2. Refractory ascites that requires paracentesis for management. 3. Known allergy to intravenous iodinated contrast agents unresponsive to prednisone pre-treatment. 4. History of prior radiation to the liver. 5. Evidence of metastatic disease. 6. Presence of a Trans-jugular intra-hepatic porto-systemic shunt (TIPS).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| To Compare the Duration of Disease Control in Treated Lesions When Utilizing SBRT Versus TACE as a Bridging Strategy for Patients With HCC Eligible for Liver Transplantation | 1 year post treatment | To compare whether or not there was disease present in treated lesions in both the SBRT and TACE arms in patients eligible for liver transplant at 1 year post treatment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Further Interventions | 2 weeks post treatment, 2 months post treatment, 5 months post treatment, every 3 months until 24 months post treatment | To compare the number of further interventions between the SBRT and TACE arms. |
| Rate of Pathological Response of Treated Lesion(s) | Review of pathology report after liver transplant | Complete pathologic response of lesions will be analyzed on the explant liver specimen after liver transplant. The pathology note will be consulted. |
| Rate of Radiological Response of Treated Lesion(s) | Baseline, 2 months post-treatment, 5 months post-treatment, every 3 months thereafter until 2 years post treatment | Response of treated lesions will be analyzed at protocol specified time frames. The response rate between both treatment arms will be compared. |
| To Compare Participants With Treatment-related Adverse Events as Assessed by CTCAE v5.0 | At each treatment, 2 weeks post treatment, 2 months post treatment, 5 months post treatment, every 3 months until 24 months post treatment | To compare treatment related adverse events between both arms, SBRT and TACE. |
| To Assess Over Survival | Baseline, during treatment, 2 months post-treatment, 5 months post-treatment, every 3 months until 24 months post treatment | Overall survival will be compared in both arms at protocol specified time frames. |
| To Assess 90 Day Post-transplant Morbidity | Disease status to be captured 90 days post-transplantation (+/- 2 weeks) | Compare the morbidity at 90 days post transplant between both arms. |
| To Assess 90 Day Post-transplant Mortality | Survival status to be captured 90 days post-transplantation (+/- 2 weeks) | Will assess the mortality of post-transplant patients between the two arms. |
| To Assess Quality of Life by Functional Assessment of Cancer Therapy-Hepatobiliary (FACT-Hep) Questionnaire | Baseline, during treatment, 2 months post-treatment, 5 months post-treatment, every 3 months until 24 months post treatment | A 45-item self-report instrument to measure health-related quality of life (HRQL) in patients with hepatobiliary cancers and is one of the most widely-used instruments in this clinical area. The FACT-Hep consists of the 27-item FACT-G, assesses HRQL, and the 18-item Hepatobiliary Subscale (HS), assesses disease-specific issues such as pain, appetite, and cramping. The FACT-G evaluates physical well-being, social/family well-being, emotional well-being, and functional well-being. Sections have a 7-day reference period and are scored from 0-4 (not at all to very much), with higher scores indicating better HRQL. Score ranges are 0-28 for physical well-being, 0-28 for social/family well-being, 0-24 for emotional well-being, 0-28 for functional well-being, and 0-72 for the HS. All subscale scores from the FACT-G and HS can be summed together to create a total FACT-Hep score, with a possible range of 0-180. The FACT-Hep takes approximately 10 minutes to complete. |
Countries
Canada, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Stereotactic Body Radiation Therapy (SBRT) Radiation Therapy
Stereotactic Body Radiation Therapy (SBRT): SBRT will be delivered in five total fractions, with at a minimum of one day between any two treatments. The entire treatment must be delivered within 15 total days. | 4 |
| Trans-Arterial Chemoembolization (TACE) Procedure/Surgery - Chemoembolization Drug: Doxorubin
Trans-Arterial Chemoembolization (TACE): First day will be administered and a second TACE will be administered after 4 weeks and subsequently if imaging is showing disease progression. Following each TACE procedure all patients will remain in hospital for observation
Doxorubin: This procedure will be completed with 2 vials of drug eluting beads each loaded with 50 mg of Doxorubin. | 5 |
| Total | 9 |
Baseline characteristics
| Characteristic | Stereotactic Body Radiation Therapy (SBRT) | Trans-Arterial Chemoembolization (TACE) | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 2 Participants | 2 Participants | 4 Participants |
| Age, Categorical Between 18 and 65 years | 2 Participants | 3 Participants | 5 Participants |
| Age, Continuous | 65.8 years STANDARD_DEVIATION 3.9 | 60.6 years STANDARD_DEVIATION 7.6 | 62.8 years STANDARD_DEVIATION 6.5 |
| 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 | 4 Participants | 5 Participants | 9 Participants |
| Region of Enrollment Canada | 1 participants | 1 participants | 2 participants |
| Region of Enrollment United States | 3 participants | 4 participants | 7 participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 4 Participants | 5 Participants | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 4 | 0 / 5 |
| other Total, other adverse events | 0 / 4 | 0 / 5 |
| serious Total, serious adverse events | 0 / 4 | 0 / 5 |
Outcome results
Primary
To Compare the Duration of Disease Control in Treated Lesions When Utilizing SBRT Versus TACE as a Bridging Strategy for Patients With HCC Eligible for Liver Transplantation
To compare whether or not there was disease present in treated lesions in both the SBRT and TACE arms in patients eligible for liver transplant at 1 year post treatment.
Time frame: 1 year post treatment
Population: Data has not been collected and therefore not analyzed for this outcome.
Secondary
Number of Further Interventions
To compare the number of further interventions between the SBRT and TACE arms.
Time frame: 2 weeks post treatment, 2 months post treatment, 5 months post treatment, every 3 months until 24 months post treatment
Population: Data has not been collected and therefore not analyzed for this outcome.
Secondary
Rate of Pathological Response of Treated Lesion(s)
Complete pathologic response of lesions will be analyzed on the explant liver specimen after liver transplant. The pathology note will be consulted.
Time frame: Review of pathology report after liver transplant
Population: Data has not been collected and therefore not analyzed for this outcome.
Secondary
Rate of Radiological Response of Treated Lesion(s)
Response of treated lesions will be analyzed at protocol specified time frames. The response rate between both treatment arms will be compared.
Time frame: Baseline, 2 months post-treatment, 5 months post-treatment, every 3 months thereafter until 2 years post treatment
Population: Data has not been collected and therefore not analyzed for this outcome
Secondary
To Assess 90 Day Post-transplant Morbidity
Compare the morbidity at 90 days post transplant between both arms.
Time frame: Disease status to be captured 90 days post-transplantation (+/- 2 weeks)
Population: Data has not been collected and therefore not analyzed for this outcome
Secondary
To Assess 90 Day Post-transplant Mortality
Will assess the mortality of post-transplant patients between the two arms.
Time frame: Survival status to be captured 90 days post-transplantation (+/- 2 weeks)
Population: Data has not been collected and therefore not analyzed for this outcome.
Secondary
To Assess Over Survival
Overall survival will be compared in both arms at protocol specified time frames.
Time frame: Baseline, during treatment, 2 months post-treatment, 5 months post-treatment, every 3 months until 24 months post treatment
Population: Data has not been collected and therefore not analyzed for this outcome
Secondary
To Assess Quality of Life by Functional Assessment of Cancer Therapy-Hepatobiliary (FACT-Hep) Questionnaire
A 45-item self-report instrument to measure health-related quality of life (HRQL) in patients with hepatobiliary cancers and is one of the most widely-used instruments in this clinical area. The FACT-Hep consists of the 27-item FACT-G, assesses HRQL, and the 18-item Hepatobiliary Subscale (HS), assesses disease-specific issues such as pain, appetite, and cramping. The FACT-G evaluates physical well-being, social/family well-being, emotional well-being, and functional well-being. Sections have a 7-day reference period and are scored from 0-4 (not at all to very much), with higher scores indicating better HRQL. Score ranges are 0-28 for physical well-being, 0-28 for social/family well-being, 0-24 for emotional well-being, 0-28 for functional well-being, and 0-72 for the HS. All subscale scores from the FACT-G and HS can be summed together to create a total FACT-Hep score, with a possible range of 0-180. The FACT-Hep takes approximately 10 minutes to complete.
Time frame: Baseline, during treatment, 2 months post-treatment, 5 months post-treatment, every 3 months until 24 months post treatment
Population: Data has not been collected and therefore not analyzed for this outcome.
Secondary
To Compare Participants With Treatment-related Adverse Events as Assessed by CTCAE v5.0
To compare treatment related adverse events between both arms, SBRT and TACE.
Time frame: At each treatment, 2 weeks post treatment, 2 months post treatment, 5 months post treatment, every 3 months until 24 months post treatment
Population: Data has not been collected and therefore not analyzed for this outcome