Liver Cancer
Conditions
Keywords
Primary liver cancer, Metastatic liver cancer
Brief summary
The purpose of this study is to determine the whether Lipiodol can be used as an imaging biomarker, predicting tumor response to therapy in patients with primary and metastatic liver cancer. Lipiodol-based transarterial chemoembolization (TACE) has been an accepted standard of care procedure for unresectable liver lesions for several decades. Lipiodol is used as a carrier for chemotherapy agents and also as an occlusion agent. In TACE procedures, Lipiodol is mixed with the chemotherapy agent(s) and delivered to the tumor via the hepatic artery, causing necrosis of the targeted tumor(s). Response to therapy will be evaluated every 1, 3 and 6 months by clinic visits, MRI/CT/PET scans and blood tests (to include assessment of liver function and tumor markers).
Interventions
DRUGLipiodol
Lipiodol is used as a carrier for chemotherapy agents and also as an occlusion agent. In TACE procedures, Lipiodol is mixed with the chemotherapy agent(s) and delivered to the tumor via the hepatic artery, causing necrosis of the targeted tumor(s).
Sponsors
Guerbet
Yale University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. 18 years of age or older. 2. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2. 3. Childs class of A or B (up to 9). 4. Hepatocellular carcinoma (HCC) is unresectable with liver-predominant disease or subject has HCC and refused surgery or subject is diagnosed hepatic metastases from any solid tumor. (Multifocal HCC is acceptable, no diffuse HCC). 5. Subject is voluntarily participating in the study and has signed the informed consent.
Exclusion criteria
1. Contraindications to doxorubicin, cisplatin, or mytomycin-c administration (or specific mixture of chemotherapy drugs to be used). 2. Evidence of severe or uncontrolled systemic diseases. 3. Congestive cardiac failure \>NYHA class 2 MI within 6 months, active coronary artery disease, cardiac arrhythmias requiring anti-arrhythmic therapy other than beta blockers or digoxin, unstable angina, or laboratory finding that in the view of the investigator makes it undesirable for the patient to participate in the trial. 4. Known allergy to Lipiodol (Ethiodol), poppy seed oil, or iodinated contrast agents (that cannot be adequately mitigated with pre-procedure medication). 5. Main portal vein thrombosis is excluded; segmental or branch portal vein thrombosis is acceptable. 6. Subject is breastfeeding. 7. Subject is pregnant
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Tumor Response by Response Evaluation Criteria in Solid Tumors (RECIST) | 30 days, 90 days, and 180 days | Lipiodol deposition in the tumor will be measured using non contrast CT. The images from the non contrast CT will also be correlated with RECIST response separately using contrast CT, MRI and PET imaging. Response rates taken at 30 days, 90 days, 180 days. Per Response Evaluation Criteria in Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR): Disappearance of all target lesions Partial Response (PR): \>= 30% decrease in the sum of the longest diameter of target lesions Overall Response (OR) = CR + PR |
| Baseline Enhancing Tumor and Response by RECIST Criteria | 30 days, 90 days, 180 days | Analysis of enhancing tumor (% of tumor that arterially enhances on MRI imaging) to correlate with responders/nonresponders by RECIST criteria. Responders are subjects that demonstrated Complete Response or Partial Response by RECIST criteria. Nonresponders are all other subjects. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Tumor Response by World Health Organization (WHO) Criteria | 6 months | Lipiodol deposition in the tumor will be measured using non contrast CT. The images from the non contrast CT will also be correlated with WHO response separately using contrast CT, MRI and PET imaging. Response rates taken at 30 days, 90 days, 180 days. Per WHO criteria: Complete Response (CR): disappearance of all lesions for \>= 4 weeks. Partial Response (PR): At least 50% decrease in sum of the products of diameters of target lesions. Overall Response: CR + PR. |
| Baseline Enhancing Tumor and Response by WHO Criteria | 30 days, 90 days, 180 days | Analysis of enhancing tumor (% of tumor that arterially enhances on MRI imaging) to correlate with responders/nonresponders by WHO criteria. Responders are subjects that demonstrated Complete Response or Partial Response by WHO criteria. Nonresponders are all other subjects. |
| Tumor Response by European Association for the Study of the Liver (EASL) Criteria | 6 months | Lipiodol deposition in the tumor will be measured using non contrast CT. The images from the non contrast CT will also be correlated with EASL response separately using contrast CT, MRI and PET imaging. Response rates taken at 30 days, 90 days, 180 days. Per EASL response: Complete Response (CR): complete disappearance of enhancing tissue in target lesions Partial Response (PR): At least 50% decrease in area of enhancing tissue in target lesions. Overall Response: CR+PR |
| Tumor Response by Modified Response Evaluation Criteria in Solid Tumors (mRECIST) | 30 days, 90 days, and 180 days | Lipiodol deposition in the tumor will be measured using non contrast CT. The images from the non contrast CT will also be correlated with mRECIST response separately using contrast CT, MRI and PET imaging. Response rates taken at 30 days, 90 days, 180 days. Per modified Response Evaluation Criteria in Solid Tumors (mRECIST): Complete Response (CR): Disappearance of all intratumoral arterial enhancement in target lesions Partial Response (PR): At least 30% decrease in the sum of the diameters of viable (enhancement in the arterial phase) target lesions Overall Response (OR) = CR + PR |
| Tumor Response by Quantitative European Association for the Study of the Liver (qEASL) Criteria | 6 months | Lipiodol deposition in the tumor will be measured using non contrast CT. The images from the non contrast CT will also be correlated with qEASL response separately using contrast CT, MRI and PET imaging. Response rates taken at 30 days, 90 days, 180 days. Per qEASL criteria: Complete Response (CR): Total disappearance of enhancing tumor volume in target lesions Partial Response (PR): At least 65% decrease in enhanced tumor volume after treatment. Overall Response: CR + PR |
| Baseline Enhancing Tumor and Response by qEASL Criteria | 30 days, 90 days, 180 days | Analysis of enhancing tumor (% of tumor that arterially enhances on MRI imaging) to correlate with responders/nonresponders by qEASL criteria. Responders are subjects that demonstrated Complete Response or Partial Response by qEASL criteria. Nonresponders are all other subjects. |
| 6-month Survival Rate of Patients With HCC and Liver Metastases Treated With Conventional TACE | 6 months | Measure the association between baseline Lipiodol deposition and the 6-month survival rate by estimating median survival for each stratum, and by testing for homogeneity using a logrank test if hazards are proportional. |
| Baseline Enhancing Tumor and Response by EASL Criteria | 30 days, 90 days, 180 days | Analysis of enhancing tumor (% of tumor that arterially enhances on MRI imaging) to correlate with responders/nonresponders by EASL criteria. Responders are subjects that demonstrated Complete Response or Partial Response by EASL criteria. Nonresponders are all other subjects. |
| Baseline Enhancing Tumor and Response by mRECIST Criteria | 30 days, 90 days, 180 days | Analysis of enhancing tumor (% of tumor that arterially enhances on MRI imaging) to correlate with responders/nonresponders by mRECIST criteria. Responders are subjects that demonstrated Complete Response or Partial Response by mRECIST criteria. Nonresponders are all other subjects. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Lipiodol Lipiodol, 10cc per TACE.
Lipiodol: Lipiodol is used as a carrier for chemotherapy agents and also as an occlusion agent. In TACE procedures, Lipiodol is mixed with the chemotherapy agent(s) and delivered to the tumor via the hepatic artery, causing necrosis of the targeted tumor(s). | 39 |
| Total | 39 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Death | 2 |
| Overall Study | Declining clinical status | 11 |
| Overall Study | Liver transplant | 2 |
| Overall Study | Lost to Follow-up | 3 |
| Overall Study | Withdrawal by Subject | 4 |
Baseline characteristics
| Characteristic | Lipiodol |
|---|---|
| Age, Continuous | 61.28 years STANDARD_DEVIATION 10.75 |
| Race/Ethnicity, Customized African American | 10 Participants |
| Race/Ethnicity, Customized Hispanic | 1 Participants |
| Race/Ethnicity, Customized Other | 5 Participants |
| Race/Ethnicity, Customized White | 23 Participants |
| Region of Enrollment United States | 39 participants |
| Sex: Female, Male Female | 13 Participants |
| Sex: Female, Male Male | 26 Participants |
| Tumor Type Cholangiocarcinoma | 8 Participants |
| Tumor Type Cutaneous melanoma | 1 Participants |
| Tumor Type Hepatocellular carcinoma | 22 Participants |
| Tumor Type Neuroendocrine: bronchial | 1 Participants |
| Tumor Type Neuroendocrine: GI | 4 Participants |
| Tumor Type Neuroendocrine: pancreatic | 2 Participants |
| Tumor Type Uveal melanoma | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 2 / 39 |
| other Total, other adverse events | 33 / 39 |
| serious Total, serious adverse events | 11 / 39 |
Outcome results
Primary
Baseline Enhancing Tumor and Response by RECIST Criteria
Analysis of enhancing tumor (% of tumor that arterially enhances on MRI imaging) to correlate with responders/nonresponders by RECIST criteria. Responders are subjects that demonstrated Complete Response or Partial Response by RECIST criteria. Nonresponders are all other subjects.
Time frame: 30 days, 90 days, 180 days
Population: 16 HCC and 14 non-HCC subjects had applicable data for analysis at 30day f/u, 9 HCC and 6 non-HCC at 90 day f/u, and 9 HCC and 4 non-HCC at 180 day f/u.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Lipiodol (HCC) | Baseline Enhancing Tumor and Response by RECIST Criteria | (30 day) Responders | 95.1 % tumor enhancement |
| Lipiodol (HCC) | Baseline Enhancing Tumor and Response by RECIST Criteria | (30 day) Nonresponders | 53.4 % tumor enhancement |
| Lipiodol (HCC) | Baseline Enhancing Tumor and Response by RECIST Criteria | (90 day) Responders | 65.2 % tumor enhancement |
| Lipiodol (HCC) | Baseline Enhancing Tumor and Response by RECIST Criteria | (90 day) Nonresponders | 50.6 % tumor enhancement |
| Lipiodol (HCC) | Baseline Enhancing Tumor and Response by RECIST Criteria | (180 day) Responders | 77.0 % tumor enhancement |
| Lipiodol (HCC) | Baseline Enhancing Tumor and Response by RECIST Criteria | (180 day) Nonresponders | 46.2 % tumor enhancement |
| Lipiodol (Non-HCC) | Baseline Enhancing Tumor and Response by RECIST Criteria | (180 day) Nonresponders | 43.1 % tumor enhancement |
| Lipiodol (Non-HCC) | Baseline Enhancing Tumor and Response by RECIST Criteria | (30 day) Responders | 97.30 % tumor enhancement |
| Lipiodol (Non-HCC) | Baseline Enhancing Tumor and Response by RECIST Criteria | (90 day) Nonresponders | 30.4 % tumor enhancement |
| Lipiodol (Non-HCC) | Baseline Enhancing Tumor and Response by RECIST Criteria | (180 day) Responders | 89.6 % tumor enhancement |
| Lipiodol (Non-HCC) | Baseline Enhancing Tumor and Response by RECIST Criteria | (30 day) Nonresponders | 50.7 % tumor enhancement |
| Lipiodol (Non-HCC) | Baseline Enhancing Tumor and Response by RECIST Criteria | (90 day) Responders | 89.6 % tumor enhancement |
| Overall | Baseline Enhancing Tumor and Response by RECIST Criteria | (30 day) Nonresponders | 52.1 % tumor enhancement |
| Overall | Baseline Enhancing Tumor and Response by RECIST Criteria | (90 day) Responders | 79.4 % tumor enhancement |
| Overall | Baseline Enhancing Tumor and Response by RECIST Criteria | (180 day) Nonresponders | 46.2 % tumor enhancement |
| Overall | Baseline Enhancing Tumor and Response by RECIST Criteria | (90 day) Nonresponders | 42.4 % tumor enhancement |
| Overall | Baseline Enhancing Tumor and Response by RECIST Criteria | (30 day) Responders | 96.2 % tumor enhancement |
| Overall | Baseline Enhancing Tumor and Response by RECIST Criteria | (180 day) Responders | 81.9 % tumor enhancement |
Comparison: Sample size of 60 achieves 80% power to detect a Pearson correlation coefficient of 0.35 with a two-sided significant level of 0.05. Sample size of 30 will allow for detecting a Pearson correlation coefficient of 0.49 in each subgroup.p-value: 0.06Wilcoxon (Mann-Whitney)
Comparison: Sample size of 60 achieves 80% power to detect a Pearson correlation coefficient of 0.35 with a two-sided significant level of 0.05. Sample size of 30 will allow for detecting a Pearson correlation coefficient of 0.49 in each subgroup.p-value: 0.09Wilcoxon (Mann-Whitney)
Comparison: Sample size of 60 achieves 80% power to detect a Pearson correlation coefficient of 0.35 with a two-sided significant level of 0.05. Sample size of 30 will allow for detecting a Pearson correlation coefficient of 0.49 in each subgroup.p-value: 0.034Wilcoxon (Mann-Whitney)
Primary
Tumor Response by Response Evaluation Criteria in Solid Tumors (RECIST)
Lipiodol deposition in the tumor will be measured using non contrast CT. The images from the non contrast CT will also be correlated with RECIST response separately using contrast CT, MRI and PET imaging. Response rates taken at 30 days, 90 days, 180 days. Per Response Evaluation Criteria in Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR): Disappearance of all target lesions Partial Response (PR): \>= 30% decrease in the sum of the longest diameter of target lesions Overall Response (OR) = CR + PR
Time frame: 30 days, 90 days, and 180 days
Population: 18 HCC and 16 non-HCC subjects had complete data for analysis at 30day f/u, 11 HCC and 7 non-HCC at 90 day f/u, and 11 HCC and 5 non-HCC at 180 day f/u.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Lipiodol (HCC) | Tumor Response by Response Evaluation Criteria in Solid Tumors (RECIST) | 30 day f/u | Responders | 1 Participants |
| Lipiodol (HCC) | Tumor Response by Response Evaluation Criteria in Solid Tumors (RECIST) | 30 day f/u | Non-responders | 17 Participants |
| Lipiodol (HCC) | Tumor Response by Response Evaluation Criteria in Solid Tumors (RECIST) | 90 day f/u | Responders | 5 Participants |
| Lipiodol (HCC) | Tumor Response by Response Evaluation Criteria in Solid Tumors (RECIST) | 90 day f/u | Non-responders | 6 Participants |
| Lipiodol (HCC) | Tumor Response by Response Evaluation Criteria in Solid Tumors (RECIST) | 180 day f/u | Responders | 4 Participants |
| Lipiodol (HCC) | Tumor Response by Response Evaluation Criteria in Solid Tumors (RECIST) | 180 day f/u | Non-responders | 7 Participants |
| Lipiodol (Non-HCC) | Tumor Response by Response Evaluation Criteria in Solid Tumors (RECIST) | 180 day f/u | Responders | 2 Participants |
| Lipiodol (Non-HCC) | Tumor Response by Response Evaluation Criteria in Solid Tumors (RECIST) | 30 day f/u | Responders | 1 Participants |
| Lipiodol (Non-HCC) | Tumor Response by Response Evaluation Criteria in Solid Tumors (RECIST) | 90 day f/u | Non-responders | 4 Participants |
| Lipiodol (Non-HCC) | Tumor Response by Response Evaluation Criteria in Solid Tumors (RECIST) | 30 day f/u | Non-responders | 15 Participants |
| Lipiodol (Non-HCC) | Tumor Response by Response Evaluation Criteria in Solid Tumors (RECIST) | 180 day f/u | Non-responders | 3 Participants |
| Lipiodol (Non-HCC) | Tumor Response by Response Evaluation Criteria in Solid Tumors (RECIST) | 90 day f/u | Responders | 3 Participants |
Secondary
6-month Survival Rate of Patients With HCC and Liver Metastases Treated With Conventional TACE
Measure the association between baseline Lipiodol deposition and the 6-month survival rate by estimating median survival for each stratum, and by testing for homogeneity using a logrank test if hazards are proportional.
Time frame: 6 months
Population: Kaplan-Meier survival analysis to estimate survival rate% at 6 months. Subjects are censored if survival is unknown at time point due to loss to followup.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Lipiodol (HCC) | 6-month Survival Rate of Patients With HCC and Liver Metastases Treated With Conventional TACE | 67.6 percentage of partcipants |
Secondary
Baseline Enhancing Tumor and Response by EASL Criteria
Analysis of enhancing tumor (% of tumor that arterially enhances on MRI imaging) to correlate with responders/nonresponders by EASL criteria. Responders are subjects that demonstrated Complete Response or Partial Response by EASL criteria. Nonresponders are all other subjects.
Time frame: 30 days, 90 days, 180 days
Population: 16 HCC and 14 non-HCC subjects had applicable data for analysis at 30day f/u, 9 HCC and 6 non-HCC at 90 day f/u, and 9 HCC and 4 non-HCC at 180 day f/u.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Lipiodol (HCC) | Baseline Enhancing Tumor and Response by EASL Criteria | (30 day) Responders | 77.0 % tumor enhancement |
| Lipiodol (HCC) | Baseline Enhancing Tumor and Response by EASL Criteria | (30 days) Nonresponders | 50.1 % tumor enhancement |
| Lipiodol (HCC) | Baseline Enhancing Tumor and Response by EASL Criteria | (90 days) Responders | 77.0 % tumor enhancement |
| Lipiodol (HCC) | Baseline Enhancing Tumor and Response by EASL Criteria | (90 days) Nonresponders | 39.1 % tumor enhancement |
| Lipiodol (HCC) | Baseline Enhancing Tumor and Response by EASL Criteria | (180 days) Responders | 71.2 % tumor enhancement |
| Lipiodol (HCC) | Baseline Enhancing Tumor and Response by EASL Criteria | (180 days) Nonresponders | 47.6 % tumor enhancement |
| Lipiodol (Non-HCC) | Baseline Enhancing Tumor and Response by EASL Criteria | (180 days) Nonresponders | 74.8 % tumor enhancement |
| Lipiodol (Non-HCC) | Baseline Enhancing Tumor and Response by EASL Criteria | (30 day) Responders | 87.8 % tumor enhancement |
| Lipiodol (Non-HCC) | Baseline Enhancing Tumor and Response by EASL Criteria | (90 days) Nonresponders | 36.9 % tumor enhancement |
| Lipiodol (Non-HCC) | Baseline Enhancing Tumor and Response by EASL Criteria | (180 days) Responders | 57.8 % tumor enhancement |
| Lipiodol (Non-HCC) | Baseline Enhancing Tumor and Response by EASL Criteria | (30 days) Nonresponders | 46.6 % tumor enhancement |
| Lipiodol (Non-HCC) | Baseline Enhancing Tumor and Response by EASL Criteria | (90 days) Responders | 62.1 % tumor enhancement |
| Overall | Baseline Enhancing Tumor and Response by EASL Criteria | (30 days) Nonresponders | 50.1 % tumor enhancement |
| Overall | Baseline Enhancing Tumor and Response by EASL Criteria | (90 days) Responders | 77.0 % tumor enhancement |
| Overall | Baseline Enhancing Tumor and Response by EASL Criteria | (180 days) Nonresponders | 60.6 % tumor enhancement |
| Overall | Baseline Enhancing Tumor and Response by EASL Criteria | (90 days) Nonresponders | 39.1 % tumor enhancement |
| Overall | Baseline Enhancing Tumor and Response by EASL Criteria | (30 day) Responders | 78.2 % tumor enhancement |
| Overall | Baseline Enhancing Tumor and Response by EASL Criteria | (180 days) Responders | 71.2 % tumor enhancement |
Comparison: Sample size of 60 achieves 80% power to detect a Pearson correlation coefficient of 0.35 with a two-sided significant level of 0.05. Sample size of 30 will allow for detecting a Pearson correlation coefficient of 0.49 in each subgroup.p-value: 0.02Wilcoxon (Mann-Whitney)
Comparison: Sample size of 60 achieves 80% power to detect a Pearson correlation coefficient of 0.35 with a two-sided significant level of 0.05. Sample size of 30 will allow for detecting a Pearson correlation coefficient of 0.49 in each subgroup.p-value: 0.029Wilcoxon (Mann-Whitney)
Comparison: Sample size of 60 achieves 80% power to detect a Pearson correlation coefficient of 0.35 with a two-sided significant level of 0.05. Sample size of 30 will allow for detecting a Pearson correlation coefficient of 0.49 in each subgroup.p-value: 0.94Wilcoxon (Mann-Whitney)
Secondary
Baseline Enhancing Tumor and Response by mRECIST Criteria
Analysis of enhancing tumor (% of tumor that arterially enhances on MRI imaging) to correlate with responders/nonresponders by mRECIST criteria. Responders are subjects that demonstrated Complete Response or Partial Response by mRECIST criteria. Nonresponders are all other subjects.
Time frame: 30 days, 90 days, 180 days
Population: 16 HCC and 14 non-HCC subjects had applicable data for analysis at 30day f/u, 9 HCC and 6 non-HCC at 90 day f/u, and 9 HCC and 4 non-HCC at 180 day f/u.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Lipiodol (HCC) | Baseline Enhancing Tumor and Response by mRECIST Criteria | (30 day) Responders | 95.1 % tumor enhancement |
| Lipiodol (HCC) | Baseline Enhancing Tumor and Response by mRECIST Criteria | (30 days) Nonresponders | 50.6 % tumor enhancement |
| Lipiodol (HCC) | Baseline Enhancing Tumor and Response by mRECIST Criteria | (90 days) Responders | 74.1 % tumor enhancement |
| Lipiodol (HCC) | Baseline Enhancing Tumor and Response by mRECIST Criteria | (90 days) Nonresponders | 41.8 % tumor enhancement |
| Lipiodol (HCC) | Baseline Enhancing Tumor and Response by mRECIST Criteria | (180 days) Responders | 74.1 % tumor enhancement |
| Lipiodol (HCC) | Baseline Enhancing Tumor and Response by mRECIST Criteria | (180 days) Nonresponders | 50.6 % tumor enhancement |
| Lipiodol (Non-HCC) | Baseline Enhancing Tumor and Response by mRECIST Criteria | (180 days) Nonresponders | 82.5 % tumor enhancement |
| Lipiodol (Non-HCC) | Baseline Enhancing Tumor and Response by mRECIST Criteria | (30 day) Responders | 53.7 % tumor enhancement |
| Lipiodol (Non-HCC) | Baseline Enhancing Tumor and Response by mRECIST Criteria | (90 days) Nonresponders | 30.4 % tumor enhancement |
| Lipiodol (Non-HCC) | Baseline Enhancing Tumor and Response by mRECIST Criteria | (180 days) Responders | 50.1 % tumor enhancement |
| Lipiodol (Non-HCC) | Baseline Enhancing Tumor and Response by mRECIST Criteria | (30 days) Nonresponders | 52.7 % tumor enhancement |
| Lipiodol (Non-HCC) | Baseline Enhancing Tumor and Response by mRECIST Criteria | (90 days) Responders | 89.6 % tumor enhancement |
| Overall | Baseline Enhancing Tumor and Response by mRECIST Criteria | (30 days) Nonresponders | 50.7 % tumor enhancement |
| Overall | Baseline Enhancing Tumor and Response by mRECIST Criteria | (90 days) Responders | 79.4 % tumor enhancement |
| Overall | Baseline Enhancing Tumor and Response by mRECIST Criteria | (180 days) Nonresponders | 53.4 % tumor enhancement |
| Overall | Baseline Enhancing Tumor and Response by mRECIST Criteria | (90 days) Nonresponders | 41.8 % tumor enhancement |
| Overall | Baseline Enhancing Tumor and Response by mRECIST Criteria | (30 day) Responders | 78.2 % tumor enhancement |
| Overall | Baseline Enhancing Tumor and Response by mRECIST Criteria | (180 days) Responders | 74.1 % tumor enhancement |
Comparison: Sample size of 60 achieves 80% power to detect a Pearson correlation coefficient of 0.35 with a two-sided significant level of 0.05. Sample size of 30 will allow for detecting a Pearson correlation coefficient of 0.49 in each subgroup.p-value: 0.19Wilcoxon (Mann-Whitney)
Comparison: Sample size of 60 achieves 80% power to detect a Pearson correlation coefficient of 0.35 with a two-sided significant level of 0.05. Sample size of 30 will allow for detecting a Pearson correlation coefficient of 0.49 in each subgroup.p-value: 0.011Wilcoxon (Mann-Whitney)
Comparison: Sample size of 60 achieves 80% power to detect a Pearson correlation coefficient of 0.35 with a two-sided significant level of 0.05. Sample size of 30 will allow for detecting a Pearson correlation coefficient of 0.49 in each subgroup.p-value: 0.94Wilcoxon (Mann-Whitney)
Secondary
Baseline Enhancing Tumor and Response by qEASL Criteria
Analysis of enhancing tumor (% of tumor that arterially enhances on MRI imaging) to correlate with responders/nonresponders by qEASL criteria. Responders are subjects that demonstrated Complete Response or Partial Response by qEASL criteria. Nonresponders are all other subjects.
Time frame: 30 days, 90 days, 180 days
Population: 16 HCC and 14 non-HCC subjects had applicable data for analysis at 30day f/u, 9 HCC and 6 non-HCC at 90 day f/u, and 9 HCC and 4 non-HCC at 180 day f/u.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Lipiodol (HCC) | Baseline Enhancing Tumor and Response by qEASL Criteria | (90 days) Responders | 71.2 % tumor enhancement |
| Lipiodol (HCC) | Baseline Enhancing Tumor and Response by qEASL Criteria | (180 days) Responders | 62.3 % tumor enhancement |
| Lipiodol (HCC) | Baseline Enhancing Tumor and Response by qEASL Criteria | (30 days) Nonresponders | 46.0 % tumor enhancement |
| Lipiodol (HCC) | Baseline Enhancing Tumor and Response by qEASL Criteria | (90 days) Nonresponders | 39.1 % tumor enhancement |
| Lipiodol (HCC) | Baseline Enhancing Tumor and Response by qEASL Criteria | (180 days) Nonresponders | 41.8 % tumor enhancement |
| Lipiodol (HCC) | Baseline Enhancing Tumor and Response by qEASL Criteria | (30 day) Responders | 74.1 % tumor enhancement |
| Lipiodol (Non-HCC) | Baseline Enhancing Tumor and Response by qEASL Criteria | (90 days) Nonresponders | 18.4 % tumor enhancement |
| Lipiodol (Non-HCC) | Baseline Enhancing Tumor and Response by qEASL Criteria | (180 days) Responders | 74.8 % tumor enhancement |
| Lipiodol (Non-HCC) | Baseline Enhancing Tumor and Response by qEASL Criteria | (30 day) Responders | 81.9 % tumor enhancement |
| Lipiodol (Non-HCC) | Baseline Enhancing Tumor and Response by qEASL Criteria | (90 days) Responders | 81.9 % tumor enhancement |
| Lipiodol (Non-HCC) | Baseline Enhancing Tumor and Response by qEASL Criteria | (30 days) Nonresponders | 50.7 % tumor enhancement |
| Overall | Baseline Enhancing Tumor and Response by qEASL Criteria | (180 days) Nonresponders | 41.8 % tumor enhancement |
| Overall | Baseline Enhancing Tumor and Response by qEASL Criteria | (30 day) Responders | 77.0 % tumor enhancement |
| Overall | Baseline Enhancing Tumor and Response by qEASL Criteria | (30 days) Nonresponders | 50.1 % tumor enhancement |
| Overall | Baseline Enhancing Tumor and Response by qEASL Criteria | (90 days) Responders | 74.1 % tumor enhancement |
| Overall | Baseline Enhancing Tumor and Response by qEASL Criteria | (90 days) Nonresponders | 36.3 % tumor enhancement |
| Overall | Baseline Enhancing Tumor and Response by qEASL Criteria | (180 days) Responders | 69.5 % tumor enhancement |
Comparison: Sample size of 60 achieves 80% power to detect a Pearson correlation coefficient of 0.35 with a two-sided significant level of 0.05. Sample size of 30 will allow for detecting a Pearson correlation coefficient of 0.49 in each subgroup.p-value: 0.06Wilcoxon (Mann-Whitney)
Comparison: Sample size of 60 achieves 80% power to detect a Pearson correlation coefficient of 0.35 with a two-sided significant level of 0.05. Sample size of 30 will allow for detecting a Pearson correlation coefficient of 0.49 in each subgroup.p-value: 0.013Wilcoxon (Mann-Whitney)
Comparison: Sample size of 60 achieves 80% power to detect a Pearson correlation coefficient of 0.35 with a two-sided significant level of 0.05. Sample size of 30 will allow for detecting a Pearson correlation coefficient of 0.49 in each subgroup.p-value: 0.67Wilcoxon (Mann-Whitney)
Secondary
Baseline Enhancing Tumor and Response by WHO Criteria
Analysis of enhancing tumor (% of tumor that arterially enhances on MRI imaging) to correlate with responders/nonresponders by WHO criteria. Responders are subjects that demonstrated Complete Response or Partial Response by WHO criteria. Nonresponders are all other subjects.
Time frame: 30 days, 90 days, 180 days
Population: 16 HCC and 14 non-HCC subjects had applicable data for analysis at 30day f/u, 9 HCC and 6 non-HCC at 90 day f/u, and 9 HCC and 4 non-HCC at 180 day f/u.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Lipiodol (HCC) | Baseline Enhancing Tumor and Response by WHO Criteria | (30 day) Responders | 95.1 % tumor enhancement |
| Lipiodol (HCC) | Baseline Enhancing Tumor and Response by WHO Criteria | (30 days) Nonresponders | 53.4 % tumor enhancement |
| Lipiodol (HCC) | Baseline Enhancing Tumor and Response by WHO Criteria | (90 days) Responders | 77.0 % tumor enhancement |
| Lipiodol (HCC) | Baseline Enhancing Tumor and Response by WHO Criteria | (90 days) Nonresponders | 46.2 % tumor enhancement |
| Lipiodol (HCC) | Baseline Enhancing Tumor and Response by WHO Criteria | (180 days) Responders | 77.0 % tumor enhancement |
| Lipiodol (HCC) | Baseline Enhancing Tumor and Response by WHO Criteria | (180 days) Nonresponders | 46.2 % tumor enhancement |
| Lipiodol (Non-HCC) | Baseline Enhancing Tumor and Response by WHO Criteria | (180 days) Nonresponders | 67.8 % tumor enhancement |
| Lipiodol (Non-HCC) | Baseline Enhancing Tumor and Response by WHO Criteria | (30 day) Responders | 97.3 % tumor enhancement |
| Lipiodol (Non-HCC) | Baseline Enhancing Tumor and Response by WHO Criteria | (90 days) Nonresponders | 30.4 % tumor enhancement |
| Lipiodol (Non-HCC) | Baseline Enhancing Tumor and Response by WHO Criteria | (180 days) Responders | 97.3 % tumor enhancement |
| Lipiodol (Non-HCC) | Baseline Enhancing Tumor and Response by WHO Criteria | (30 days) Nonresponders | 50.7 % tumor enhancement |
| Lipiodol (Non-HCC) | Baseline Enhancing Tumor and Response by WHO Criteria | (90 days) Responders | 89.6 % tumor enhancement |
| Overall | Baseline Enhancing Tumor and Response by WHO Criteria | (30 days) Nonresponders | 52.1 % tumor enhancement |
| Overall | Baseline Enhancing Tumor and Response by WHO Criteria | (90 days) Responders | 81.9 % tumor enhancement |
| Overall | Baseline Enhancing Tumor and Response by WHO Criteria | (180 days) Nonresponders | 50.6 % tumor enhancement |
| Overall | Baseline Enhancing Tumor and Response by WHO Criteria | (90 days) Nonresponders | 42.1 % tumor enhancement |
| Overall | Baseline Enhancing Tumor and Response by WHO Criteria | (30 day) Responders | 96.2 % tumor enhancement |
| Overall | Baseline Enhancing Tumor and Response by WHO Criteria | (180 days) Responders | 87.5 % tumor enhancement |
Comparison: Sample size of 60 achieves 80% power to detect a Pearson correlation coefficient of 0.35 with a two-sided significant level of 0.05. Sample size of 30 will allow for detecting a Pearson correlation coefficient of 0.49 in each subgroup.p-value: 0.06Wilcoxon (Mann-Whitney)
Comparison: Sample size of 60 achieves 80% power to detect a Pearson correlation coefficient of 0.35 with a two-sided significant level of 0.05. Sample size of 30 will allow for detecting a Pearson correlation coefficient of 0.49 in each subgroup.p-value: 0.017Wilcoxon (Mann-Whitney)
Comparison: Sample size of 60 achieves 80% power to detect a Pearson correlation coefficient of 0.35 with a two-sided significant level of 0.05. Sample size of 30 will allow for detecting a Pearson correlation coefficient of 0.49 in each subgroup.p-value: 0.08Wilcoxon (Mann-Whitney)
Secondary
Tumor Response by European Association for the Study of the Liver (EASL) Criteria
Lipiodol deposition in the tumor will be measured using non contrast CT. The images from the non contrast CT will also be correlated with EASL response separately using contrast CT, MRI and PET imaging. Response rates taken at 30 days, 90 days, 180 days. Per EASL response: Complete Response (CR): complete disappearance of enhancing tissue in target lesions Partial Response (PR): At least 50% decrease in area of enhancing tissue in target lesions. Overall Response: CR+PR
Time frame: 6 months
Population: 18 HCC and 14 non-HCC subjects had complete data for analysis at 30day f/u, 11 HCC and 7 non-HCC at 90 day f/u, and 11 HCC and 5 non-HCC at 180 day f/u.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Lipiodol (HCC) | Tumor Response by European Association for the Study of the Liver (EASL) Criteria | 30 day f/u | Non-responders | 7 Participants |
| Lipiodol (HCC) | Tumor Response by European Association for the Study of the Liver (EASL) Criteria | 30 day f/u | Responders | 11 Participants |
| Lipiodol (HCC) | Tumor Response by European Association for the Study of the Liver (EASL) Criteria | 180 day f/u | Responders | 7 Participants |
| Lipiodol (HCC) | Tumor Response by European Association for the Study of the Liver (EASL) Criteria | 90 day f/u | Responders | 7 Participants |
| Lipiodol (HCC) | Tumor Response by European Association for the Study of the Liver (EASL) Criteria | 180 day f/u | Non-responders | 4 Participants |
| Lipiodol (HCC) | Tumor Response by European Association for the Study of the Liver (EASL) Criteria | 90 day f/u | Non-responders | 4 Participants |
| Lipiodol (Non-HCC) | Tumor Response by European Association for the Study of the Liver (EASL) Criteria | 180 day f/u | Non-responders | 1 Participants |
| Lipiodol (Non-HCC) | Tumor Response by European Association for the Study of the Liver (EASL) Criteria | 30 day f/u | Responders | 2 Participants |
| Lipiodol (Non-HCC) | Tumor Response by European Association for the Study of the Liver (EASL) Criteria | 30 day f/u | Non-responders | 12 Participants |
| Lipiodol (Non-HCC) | Tumor Response by European Association for the Study of the Liver (EASL) Criteria | 90 day f/u | Responders | 5 Participants |
| Lipiodol (Non-HCC) | Tumor Response by European Association for the Study of the Liver (EASL) Criteria | 90 day f/u | Non-responders | 2 Participants |
| Lipiodol (Non-HCC) | Tumor Response by European Association for the Study of the Liver (EASL) Criteria | 180 day f/u | Responders | 4 Participants |
Secondary
Tumor Response by Modified Response Evaluation Criteria in Solid Tumors (mRECIST)
Lipiodol deposition in the tumor will be measured using non contrast CT. The images from the non contrast CT will also be correlated with mRECIST response separately using contrast CT, MRI and PET imaging. Response rates taken at 30 days, 90 days, 180 days. Per modified Response Evaluation Criteria in Solid Tumors (mRECIST): Complete Response (CR): Disappearance of all intratumoral arterial enhancement in target lesions Partial Response (PR): At least 30% decrease in the sum of the diameters of viable (enhancement in the arterial phase) target lesions Overall Response (OR) = CR + PR
Time frame: 30 days, 90 days, and 180 days
Population: 18 HCC and 14 non-HCC subjects had complete data for analysis at 30day f/u, 11 HCC and 7 non-HCC at 90 day f/u, and 11 HCC and 5 non-HCC at 180 day f/u.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Lipiodol (HCC) | Tumor Response by Modified Response Evaluation Criteria in Solid Tumors (mRECIST) | 30 day f/u | Responders | 9 Participants |
| Lipiodol (HCC) | Tumor Response by Modified Response Evaluation Criteria in Solid Tumors (mRECIST) | 30 day f/u | Non-responders | 9 Participants |
| Lipiodol (HCC) | Tumor Response by Modified Response Evaluation Criteria in Solid Tumors (mRECIST) | 90 day f/u | Responders | 6 Participants |
| Lipiodol (HCC) | Tumor Response by Modified Response Evaluation Criteria in Solid Tumors (mRECIST) | 90 day f/u | Non-responders | 5 Participants |
| Lipiodol (HCC) | Tumor Response by Modified Response Evaluation Criteria in Solid Tumors (mRECIST) | 180 day f/u | Responders | 6 Participants |
| Lipiodol (HCC) | Tumor Response by Modified Response Evaluation Criteria in Solid Tumors (mRECIST) | 180 day f/u | Non-responders | 5 Participants |
| Lipiodol (Non-HCC) | Tumor Response by Modified Response Evaluation Criteria in Solid Tumors (mRECIST) | 180 day f/u | Responders | 2 Participants |
| Lipiodol (Non-HCC) | Tumor Response by Modified Response Evaluation Criteria in Solid Tumors (mRECIST) | 30 day f/u | Responders | 2 Participants |
| Lipiodol (Non-HCC) | Tumor Response by Modified Response Evaluation Criteria in Solid Tumors (mRECIST) | 90 day f/u | Non-responders | 4 Participants |
| Lipiodol (Non-HCC) | Tumor Response by Modified Response Evaluation Criteria in Solid Tumors (mRECIST) | 30 day f/u | Non-responders | 12 Participants |
| Lipiodol (Non-HCC) | Tumor Response by Modified Response Evaluation Criteria in Solid Tumors (mRECIST) | 180 day f/u | Non-responders | 3 Participants |
| Lipiodol (Non-HCC) | Tumor Response by Modified Response Evaluation Criteria in Solid Tumors (mRECIST) | 90 day f/u | Responders | 3 Participants |
Secondary
Tumor Response by Quantitative European Association for the Study of the Liver (qEASL) Criteria
Lipiodol deposition in the tumor will be measured using non contrast CT. The images from the non contrast CT will also be correlated with qEASL response separately using contrast CT, MRI and PET imaging. Response rates taken at 30 days, 90 days, 180 days. Per qEASL criteria: Complete Response (CR): Total disappearance of enhancing tumor volume in target lesions Partial Response (PR): At least 65% decrease in enhanced tumor volume after treatment. Overall Response: CR + PR
Time frame: 6 months
Population: 16 HCC and 14 non-HCC subjects had complete data for qEASL analysis at 30day f/u, 9 HCC and 7 non-HCC at 90 day f/u, and 9 HCC and 5 non-HCC at 180 day f/u.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Lipiodol (HCC) | Tumor Response by Quantitative European Association for the Study of the Liver (qEASL) Criteria | 30 day f/u | Responders | 6 Participants |
| Lipiodol (HCC) | Tumor Response by Quantitative European Association for the Study of the Liver (qEASL) Criteria | 30 day f/u | Non-responders | 10 Participants |
| Lipiodol (HCC) | Tumor Response by Quantitative European Association for the Study of the Liver (qEASL) Criteria | 90 day f/u | Responders | 5 Participants |
| Lipiodol (HCC) | Tumor Response by Quantitative European Association for the Study of the Liver (qEASL) Criteria | 90 day f/u | Non-responders | 4 Participants |
| Lipiodol (HCC) | Tumor Response by Quantitative European Association for the Study of the Liver (qEASL) Criteria | 180 day f/u | Responders | 6 Participants |
| Lipiodol (HCC) | Tumor Response by Quantitative European Association for the Study of the Liver (qEASL) Criteria | 180 day f/u | Non-responders | 3 Participants |
| Lipiodol (Non-HCC) | Tumor Response by Quantitative European Association for the Study of the Liver (qEASL) Criteria | 180 day f/u | Responders | 5 Participants |
| Lipiodol (Non-HCC) | Tumor Response by Quantitative European Association for the Study of the Liver (qEASL) Criteria | 30 day f/u | Responders | 1 Participants |
| Lipiodol (Non-HCC) | Tumor Response by Quantitative European Association for the Study of the Liver (qEASL) Criteria | 90 day f/u | Non-responders | 3 Participants |
| Lipiodol (Non-HCC) | Tumor Response by Quantitative European Association for the Study of the Liver (qEASL) Criteria | 30 day f/u | Non-responders | 13 Participants |
| Lipiodol (Non-HCC) | Tumor Response by Quantitative European Association for the Study of the Liver (qEASL) Criteria | 180 day f/u | Non-responders | 0 Participants |
| Lipiodol (Non-HCC) | Tumor Response by Quantitative European Association for the Study of the Liver (qEASL) Criteria | 90 day f/u | Responders | 4 Participants |
Secondary
Tumor Response by World Health Organization (WHO) Criteria
Lipiodol deposition in the tumor will be measured using non contrast CT. The images from the non contrast CT will also be correlated with WHO response separately using contrast CT, MRI and PET imaging. Response rates taken at 30 days, 90 days, 180 days. Per WHO criteria: Complete Response (CR): disappearance of all lesions for \>= 4 weeks. Partial Response (PR): At least 50% decrease in sum of the products of diameters of target lesions. Overall Response: CR + PR.
Time frame: 6 months
Population: 18 HCC and 14 non-HCC subjects had complete data for analysis at 30day f/u, 11 HCC and 7 non-HCC at 90 day f/u, and 11 HCC and 5 non-HCC at 180 day f/u.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Lipiodol (HCC) | Tumor Response by World Health Organization (WHO) Criteria | 30 day f/u | Responders | 2 Participants |
| Lipiodol (HCC) | Tumor Response by World Health Organization (WHO) Criteria | 30 day f/u | Non-responders | 16 Participants |
| Lipiodol (HCC) | Tumor Response by World Health Organization (WHO) Criteria | 90 day f/u | Responders | 4 Participants |
| Lipiodol (HCC) | Tumor Response by World Health Organization (WHO) Criteria | 90 day f/u | Non-responders | 7 Participants |
| Lipiodol (HCC) | Tumor Response by World Health Organization (WHO) Criteria | 180 day f/u | Responders | 4 Participants |
| Lipiodol (HCC) | Tumor Response by World Health Organization (WHO) Criteria | 180 day f/u | Non-responders | 7 Participants |
| Lipiodol (Non-HCC) | Tumor Response by World Health Organization (WHO) Criteria | 180 day f/u | Responders | 2 Participants |
| Lipiodol (Non-HCC) | Tumor Response by World Health Organization (WHO) Criteria | 30 day f/u | Responders | 1 Participants |
| Lipiodol (Non-HCC) | Tumor Response by World Health Organization (WHO) Criteria | 90 day f/u | Non-responders | 4 Participants |
| Lipiodol (Non-HCC) | Tumor Response by World Health Organization (WHO) Criteria | 30 day f/u | Non-responders | 15 Participants |
| Lipiodol (Non-HCC) | Tumor Response by World Health Organization (WHO) Criteria | 180 day f/u | Non-responders | 3 Participants |
| Lipiodol (Non-HCC) | Tumor Response by World Health Organization (WHO) Criteria | 90 day f/u | Responders | 3 Participants |