Hepatocellular Carcinoma
Conditions
Keywords
Unresectable Hepatocellular Carcinoma, Radioembolization, Radiation Segmentectomy
Brief summary
The aim of this pilot study is to assess the efficacy of radiation segmentectomy with Theraspheres in patients with unresectable hepatocellular carcinoma that would qualify for thermal ablation as per the BCLC guidelines, but are unable to receive thermal ablation due to unfavorable location of target lesions.
Interventions
RADIATIONRadiation Segmentectomy
The administration of radioactivity in a branch of an artery of the liver
Sponsors
Icahn School of Medicine at Mount Sinai
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Individuals with the targeted medical condition is given the experimental therapy and then followed over time to observe their response.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age greater than 18 years, regardless of race or gender * Hepatocellular Carcinoma confirmed by histology for non-cirrhotic patients or non-invasive criteria according to AASLD for cirrhotic patients * Child-Pugh class A or B7 without ascites * Single tumor nodule ≤ 3 cm with a maximum distance of 5 mm from portal vein, hepatic vein, inferior vena cava, diaphragm, heart, stomach, bowel, liver capsule, gallbladder, bile duct * No prior locoregional treatment or external beam therapy of current HCC (recurrent HCC after resection may be included) * No confirmed extrahepatic metastases * No evidence of macrovascular invasion * ECOG 0 * Albumin \> 3.0 g/dL * PLT ≥ 40 x103/μL * WBC ≥ 1.5 x103/μL * AST/ALT ≤ 5 times the upper limit of normal (U/L) * Creatinine ≤ 2.0 mg /dL * No indication for any possible curative treatment after multidisciplinary assessment (surgery, ablation) * No contraindication to angiography or selective visceral catheterization * No history of severe allergy or intolerance to contrast agents, narcotics, sedatives. * Negative serum pregnancy test * Signed informed consent form
Exclusion criteria
* Not meeting the inclusion criteria
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Local Tumor Response According to mRECIST | 2 years | Efficacy of 90Yttrium (Y90) Radiation Segmentectomy on Unresectable Hepatocellular Carcinoma as measured by tumor response according to mRECIST. CR = Disappearance of any intratumoral arterial enhancement in all target lesions PR = At least a 30% decrease in the diameter of the viable (enhancement in the arterial phase) target lesion SD = Any cases that do not qualify for either partial response or progressive disease PD = An increase of at least 20% in the diameter of viable (enhancing) target lesion |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cumulative Incidence of Participants With Local Progression | 1 year and 2 years | Cumulative incidence function estimation of the incidence of the occurrence of local progression (event) at 1 year and 2 years while taking the competing risk of transplant into account. Local progression was defined per modified Response Evaluation Criteria In Solid Tumors Criteria (mRECIST) for target lesions and assessed by MRI with local progression defined as an \>20% increase in the diameter of the viable (enhancing) target lesion, taking as a reference of the baseline enhancing tumor size. |
| Quantifying Dose to Target Lesion | 0 days | The dose was calculated using PET/CT calculated dose estimation delivered to the tumor. Counts on PET/CT post-treatment were used to estimate the dose delivered to the tumor. |
| Median Time to Progression (TTP) | 2 years | Time until progression of the target lesion and overall disease based on mRECIST |
| Number of Participants With Access Site-related Adverse Events | For 2 years with visits 6 weeks post treatment then every 3 months since treatment for 24 months for assessment of laboratory and clinical symptoms | Number of participants with access site-related adverse events |
| Number of Participants With Treatment-related Laboratory Adverse Events | For 2 years with visits 6 weeks post treatment then every 3 months since treatment for 24 months for assessment of laboratory changes | Number of participants with treatment-related laboratory adverse events assessed 6 weeks post-treatment then every 3 months since treatment for 24 months |
| Number of Treatment-related Adverse Events | For 2 years with visits 6 weeks post treatment then every 3 months since treatment for 24 months for assessment of laboratory and clinical symptoms | Number of treatment related adverse events according to the National Cancer Institute Common Terminology Criteria for Adverse Events v 5.0 (CTCAE). |
Countries
United States
Participant flow
Recruitment details
Individuals were enrolled between Aug 3, 2016, and April 4, 2019
Participants by arm
| Arm | Count |
|---|---|
| Radiation Segmentectomy Radiation Segmentectomy on Resectable HCC on patients diagnosed with hepatocellular carcinoma | 29 |
| Total | 29 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Lost to Follow-up | 5 |
Baseline characteristics
| Characteristic | Radiation Segmentectomy | — |
|---|---|---|
| Age, Continuous | 63.4 years STANDARD_DEVIATION 8.4 | — |
| Albumin-bilirubin grade (ALBI) Albumin-bilirubin grade 1 | 7 Participants | — |
| Albumin-bilirubin grade (ALBI) Albumin-bilirubin grade 2 | 22 Participants | — |
| Ascites | 1 Participants | — |
| Calculated dose to the perfused segment | 584 Gy | — |
| Cause of liver disease Alcohol | 7 Participants | — |
| Cause of liver disease Haemochromatosis | 1 Participants | — |
| Cause of liver disease Hepatitis B virus | 3 Participants | — |
| Cause of liver disease Hepatitis C virus | 13 Participants | — |
| Cause of liver disease Non-alcoholic steatohepatitis | 5 Participants | — |
| Cause of liver disease Sarcoidosis | 1 Participants | — |
| Child-Pugh score A5 | 14 Participants | — |
| Child-Pugh score A6 | 12 Participants | — |
| Child-Pugh score B7 | 3 Participants | — |
| Distribution of Perfused Liver Volumes 100-200 cc | 12 Participants | — |
| Distribution of Perfused Liver Volumes <100 cc | 9 Participants | — |
| Distribution of Perfused Liver Volumes >200 cc | 8 Participants | — |
| Liver segment tumor distribution 1 - caudate lobe | 0 Participants | — |
| Liver segment tumor distribution 2 - left of the left hepatic vein and falciform ligament and superior to the portal plane | 5 Participants | — |
| Liver segment tumor distribution 3 - left of the left hepatic vein and falciform ligament and inferior to the portal plane | 0 Participants | — |
| Liver segment tumor distribution 4 - between the left and middle hepatic veins - subcardiac location | 8 Participants | — |
| Liver segment tumor distribution 5 - located below the portal plane between the middle and right hepatic veins | 2 Participants | — |
| Liver segment tumor distribution 6 - located below the portal plane to the right of the right hepatic vein | 5 Participants | — |
| Liver segment tumor distribution 7 - located above the portal plane to the right of the right hepatic vein | 3 Participants | — |
| Liver segment tumor distribution 8 - located above the portal plane between the middle and right hepatic veins | 11 Participants | — |
| Lobar volume Left | 439.0 mL | — |
| Lobar volume Right | 896.7 mL | — |
| Location Central | 1 Participants | — |
| Location Peripheral | 28 Participants | — |
| Lung shunt fraction (LSF) | 4 percentage reaching lung | — |
| Number of injection locations 1 | 24 Participants | — |
| Number of injection locations 2 | 5 Participants | — |
| Perfused liver volume | 153.6 mL STANDARD_DEVIATION 99.2 | — |
| Race and Ethnicity Not Collected | — | — Participants |
| Sex: Female, Male Female | 6 Participants | — |
| Sex: Female, Male Male | 23 Participants | — |
| Tumor diameter | 2.1 cm STANDARD_DEVIATION 0.4 | — |
| α-Fetoprotein | 5 ng/mL | — |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 1 / 29 |
| other Total, other adverse events | 26 / 29 |
| serious Total, serious adverse events | 0 / 29 |
Outcome results
Primary
Number of Participants With Local Tumor Response According to mRECIST
Efficacy of 90Yttrium (Y90) Radiation Segmentectomy on Unresectable Hepatocellular Carcinoma as measured by tumor response according to mRECIST. CR = Disappearance of any intratumoral arterial enhancement in all target lesions PR = At least a 30% decrease in the diameter of the viable (enhancement in the arterial phase) target lesion SD = Any cases that do not qualify for either partial response or progressive disease PD = An increase of at least 20% in the diameter of viable (enhancing) target lesion
Time frame: 2 years
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Radiation Segmentectomy | Number of Participants With Local Tumor Response According to mRECIST | CR - Complete response | 26 Participants |
| Radiation Segmentectomy | Number of Participants With Local Tumor Response According to mRECIST | PR - Partial response | 0 Participants |
| Radiation Segmentectomy | Number of Participants With Local Tumor Response According to mRECIST | SD - Stable disease | 0 Participants |
| Radiation Segmentectomy | Number of Participants With Local Tumor Response According to mRECIST | PD - Progressive disease | 3 Participants |
Secondary
Cumulative Incidence of Participants With Local Progression
Cumulative incidence function estimation of the incidence of the occurrence of local progression (event) at 1 year and 2 years while taking the competing risk of transplant into account. Local progression was defined per modified Response Evaluation Criteria In Solid Tumors Criteria (mRECIST) for target lesions and assessed by MRI with local progression defined as an \>20% increase in the diameter of the viable (enhancing) target lesion, taking as a reference of the baseline enhancing tumor size.
Time frame: 1 year and 2 years
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Radiation Segmentectomy | Cumulative Incidence of Participants With Local Progression | 1 years | 4 percentage of participants |
| Radiation Segmentectomy | Cumulative Incidence of Participants With Local Progression | 2 years | 12 percentage of participants |
Secondary
Median Time to Progression (TTP)
Time until progression of the target lesion and overall disease based on mRECIST
Time frame: 2 years
Population: Data for participants who had target lesion progression only
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Radiation Segmentectomy | Median Time to Progression (TTP) | NA days |
Secondary
Number of Participants With Access Site-related Adverse Events
Number of participants with access site-related adverse events
Time frame: For 2 years with visits 6 weeks post treatment then every 3 months since treatment for 24 months for assessment of laboratory and clinical symptoms
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Radiation Segmentectomy | Number of Participants With Access Site-related Adverse Events | Arterial injury | 1 Participants |
| Radiation Segmentectomy | Number of Participants With Access Site-related Adverse Events | Hematoma (minor) | 4 Participants |
| Radiation Segmentectomy | Number of Participants With Access Site-related Adverse Events | None | 24 Participants |
Secondary
Number of Participants With Treatment-related Laboratory Adverse Events
Number of participants with treatment-related laboratory adverse events assessed 6 weeks post-treatment then every 3 months since treatment for 24 months
Time frame: For 2 years with visits 6 weeks post treatment then every 3 months since treatment for 24 months for assessment of laboratory changes
Population: All Patients
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Radiation Segmentectomy | Number of Participants With Treatment-related Laboratory Adverse Events | Leukopenia | 13 Participants |
| Radiation Segmentectomy | Number of Participants With Treatment-related Laboratory Adverse Events | Anemia | 3 Participants |
| Radiation Segmentectomy | Number of Participants With Treatment-related Laboratory Adverse Events | Thrombocytopenia | 6 Participants |
| Radiation Segmentectomy | Number of Participants With Treatment-related Laboratory Adverse Events | AST or ALT increased | 4 Participants |
| Radiation Segmentectomy | Number of Participants With Treatment-related Laboratory Adverse Events | ALP increased | 4 Participants |
| Radiation Segmentectomy | Number of Participants With Treatment-related Laboratory Adverse Events | Total blood bilirubin increased | 4 Participants |
| Radiation Segmentectomy | Number of Participants With Treatment-related Laboratory Adverse Events | Albumin decreased | 6 Participants |
| Radiation Segmentectomy | Number of Participants With Treatment-related Laboratory Adverse Events | Creatinine increased | 3 Participants |
| Radiation Segmentectomy | Number of Participants With Treatment-related Laboratory Adverse Events | International normalised ratio increased | 1 Participants |
Secondary
Number of Treatment-related Adverse Events
Number of treatment related adverse events according to the National Cancer Institute Common Terminology Criteria for Adverse Events v 5.0 (CTCAE).
Time frame: For 2 years with visits 6 weeks post treatment then every 3 months since treatment for 24 months for assessment of laboratory and clinical symptoms
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Radiation Segmentectomy | Number of Treatment-related Adverse Events | fatigue | 9 events |
| Radiation Segmentectomy | Number of Treatment-related Adverse Events | nausea, vomiting, or anorexia | 7 events |
| Radiation Segmentectomy | Number of Treatment-related Adverse Events | abdominal discomfort | 6 events |
| Radiation Segmentectomy | Number of Treatment-related Adverse Events | ascites | 1 events |
| Radiation Segmentectomy | Number of Treatment-related Adverse Events | laboratory changes | 24 events |
Secondary
Quantifying Dose to Target Lesion
The dose was calculated using PET/CT calculated dose estimation delivered to the tumor. Counts on PET/CT post-treatment were used to estimate the dose delivered to the tumor.
Time frame: 0 days
Population: Dose delivered to the tumour was calculated for 26 (90%) patients with 90Y PET CT imaging. Three (7%) patients were excluded due to technical issues.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Radiation Segmentectomy | Quantifying Dose to Target Lesion | 1004.6 Gy |