Clinical trial NCT01817205: Combined Chemoembolization and Systemic Hyperthermia for Unresectable Hepatocellular Carcinoma
Official title: A Pilot Study on the Feasibility of Combined Chemoembolization and Adjuvant Systemic Hyperthermia for Palliative Treatment of Unresectable Hepatocellular Carcinoma(HCC)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Hepatocellular Carcinoma
Lead sponsor: Chinese University of Hong Kong
Sponsor class: OTHER
Collaborators: name: Prince of Wales Hospital, Shatin, Hong Kong
First posted: 2013-03-25
Enrollment: 8
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The objective is to evaluate the safety and therapeutic effect of combined hyperthermia and TACE for unresectable HCC

Detailed description: 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.

Eligibility criteria: 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

Primary outcomes:
measure: dose limiting toxicity
timeFrame: 30 days from the study treatment
Secondary outcomes:
measure: adverse event of treatment
timeFrame: within 6 months of treatment
measure: imaging evidence of objective tumor response
timeFrame: 3 and 6 months after treatment
measure: treatment response by alphafetoprotein
timeFrame: 6 months after treatment
Other outcomes:
Locations:
city: Hong Kong
country: Hong Kong
facility: Department of Clinical Oncology, Prince of Wales Hospital, The Chinese University of Hong Kong
city: Hong Kong
country: Hong Kong
facility: Department of Imaging and Interventional Radiology, Prince of Wales Hospital, The Chinese University of Hong Kong
Study officials:
affiliation: Chinese University of Hong Kong
name: Simon CH Yu, MD, FRCR
role: PRINCIPAL_INVESTIGATOR
References: