Lipiodol as an Imaging Biomarker in Patients With Primary and Metastatic Liver Cancer

Phase 2

Completed

Conditions: Liver Cancer

Interventions: Drug: Lipiodol

Registration Number: NCT01877187

Lead Sponsor: Yale University

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).

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 39

Inclusion Criteria

18 years of age or older.
Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2.
Childs class of A or B (up to 9).
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).
Subject is voluntarily participating in the study and has signed the informed consent.

Exclusion Criteria

Contraindications to doxorubicin, cisplatin, or mytomycin-c administration (or specific mixture of chemotherapy drugs to be used).
Evidence of severe or uncontrolled systemic diseases.
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.
Known allergy to Lipiodol (Ethiodol), poppy seed oil, or iodinated contrast agents (that cannot be adequately mitigated with pre-procedure medication).
Main portal vein thrombosis is excluded; segmental or branch portal vein thrombosis is acceptable.
Subject is breastfeeding.
Subject is pregnant

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Lipiodol	Lipiodol	Lipiodol, 10cc per TACE.

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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
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.
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.
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
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.
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
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.