Combined Chemoembolization and Systemic Hyperthermia for Unresectable Hepatocellular Carcinoma

Study Overview
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Brief Summary
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The objective is to evaluate the safety and therapeutic effect of combined hyperthermia and TACE for unresectable HCC

Detailed Description
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Most patients with Hepatocellular carcinoma (HCC) are diagnosed at an intermediate and advanced stage when the tumors become unresectable. Transcatheter arterial chemoembolization (TACE) has been shown to be effective in prolongation of survival for patients with unresectable HCC and generally adopted as a standard palliative treatment option for patients with intermediate stage HCC. However, the therapeutic effect of TACE in terms of objective tumor response is variable and modest (27%-40%), indicating that there is actually much room for improvement in the treatment. In many cases, patients with intrahepatic HCC uncontrolled after TACE treatment may not be suitable for other treatment options because of their physical condition. For these patients, repeat TACE combined with adjuvant systemic hyperthermia may offer a chance of disease control.

Official Title
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A Pilot Study on the Feasibility of Combined Chemoembolization and Adjuvant Systemic Hyperthermia for Palliative Treatment of Unresectable Hepatocellular Carcinoma(HCC)

Conditions
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Hepatocellular Carcinoma

Intervention / Treatment
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* Procedure: TACE with Hyperthermia Treatment


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient factor Age between 18 and 75 Child-Pugh A cirrhosis Eastern Cooperative Oncology Group(ECOG) performance status Grade 2 or below No serious concurrent medical illness Prior treatment for HCC including surgery, local ablation, or transarterial treatments allowed Imaging evidence of poor intralesional treatment response or disease progression despite transarterial treatment Platelet count ≥ 50 10^9/L Tumor factor HCC diagnosed by typical enhancement patterns on cross sectional imaging or histology Unresectable and locally advanced disease without extra-hepatic disease Hypervascular lesions on CT Greatest dimension of the largest tumor ≤15cm Exclusion Criteria: Patient factor History of significant concurrent medical illness such as ischemic heart disease or heart failure Metallic body implants, not including dental fillings Serum creatinine level > 130 umol/L Presence of biliary obstruction not amenable to drainage Child-Pugh B or C cirrhosis Unable to give consent Evidence of impaired liver function History of hepatic encephalopathy Intractable ascites not controllable by medical therapy History of variceal bleeding within last 3 months Serum total bilirubin level >25 umol/L for the first 5 patients, serum total bilirubin level >35 umol/L for the second 5 patients Serum albumin level < 30g/L International normalized ratio(INR) >1.3 Tumor factor Presence of extrahepatic metastasis Infiltrative lesion Vascular invasion Hepatic artery thrombosis Partial or complete thrombosis of the main portal vein Tumor invasion of portal branch of contralateral lobe Hepatic vein tumor thrombus Significant arterioportal shunt Significant arteriovenous shunt Contraindication for hyperthermia Known brain metastasis Recent stroke or cerebral hemorrhage within last 6 months Poorly controlled epilepsy Poorly controlled cardiac arrhythmias Myocardial infarction within last 6 months Unstable angina within last 6 months Poorly controlled hypertension Poorly controlled diabetes History of malignant hyperthermia Photodermatosis Pregnancy Lactation Serious infection Grade 3 or above adverse event in serological total bilirubin or albumin according to Version 4.0 of National Cancer Institute Common Terminology Criteria for Adverse Events Elevation of serum alanine transaminase ≥ 10 times upper limit of normal

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: TACE with Hyperthermia treatment<br>Interventions: TACE to all liver lesions and two sessions of systemic hyperthermia performed at 24 hours and 48 hours respectively after TACE. | Procedure: TACE with Hyperthermia Treatment<br>* Transcatheter arterial chemoembolization (TACE) is performed under local anesthesia with right femoral puncture. The feeding lobar hepatic artery is selectively catheterized for drug delivery. Systemic hyperthermia is induced with an external energy source using microwave electromagnetic energy, with the patient lying supine on the treatment bed of the hyperthermia equipment, exposing the abdomen to the microwave transmitter.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| dose limiting toxicity |  | 30 days from the study treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| adverse event of treatment |  | within 6 months of treatment | 
| imaging evidence of objective tumor response |  | 3 and 6 months after treatment | 
| treatment response by alphafetoprotein |  | 6 months after treatment |