Clinical trial NCT00554905: Radiofrequency Ablation With or With Transcatheter Arterial Embolization for Hepatocellular Carcinoma
Official title: Radiofrequency Ablation With or With Transcatheter Arterial Embolization for Hepatocellular Carcinoma
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Hepatocellular Carcinoma
Liver Cancer
Keywords: ablation
catheter
Carcinoma, Hepatocellular
therapy
Chemoembolization, Therapeutic
Humans
Liver Neoplasms
Lead sponsor: Sun Yat-sen University
Sponsor class: OTHER
First posted: 2007-11-07
Enrollment: 180
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to prospectively evaluate whether combined RFA and TACE (RFA-TACE) result in better survival outcomes than RFA alone in patients with HCC.

Detailed description: Local ablation is a safe and effective therapy for patients who cannot undergo resection, or as a bridge to transplantation. Of the various percutaneous local ablative therapies, radiofrequency ablation (RFA) has attracted the greatest interest because of its effectiveness and safety for small HCC ≤ 5.0cm, with a 3-year survival rate of 62% to 68%, a low treatment morbidity of 0% to 12%, and a low treatment mortality of 0% to 1%. Prospective randomized trials have shown RFA to be better than percutaneous ethanol injection (PEI) in producing a higher rate of complete tumor necrosis with fewer numbers of treatment sessions and better survival.

Unfortunately, the complete tumor necrosis rate for tumors larger than 5cm is less favorable, and the local recurrence rate can be as high as 20% even in small HCC less than 3.5cm. The high local recurrence rate may be due to residual cancer cells not killed by RFA or adjacent microscopic satellite tumor nodules.

Transcatheter Arterial Chemoembolization (TACE) is proved to be an effective and palliative therapy for unresectable HCC. And some studies showed that combined TACE and RFA may produce superior tumor control than RFA alone and reduce local recurrence rate. In a study by Yamakado et al., 64 patients with 92 tumors underwent RFA within two weeks after TACE. The intrahepatic recurrence rates were 15% at 1 year and 43% at 2years, the 1, and 2, year overall survivals were 100% and 93%, respectively. These results appeared favorable, but there has not a prospective randomized controlled study to compare RFA combine with TACE versus RFA alone.

Thus the purpose of our study was to prospectively evaluate whether combined RFA and TACE (RFA-TACE) result in better survival outcomes than RFA alone in patients with HCC.

Eligibility criteria: Inclusion Criteria:

* Age 18 - 75 years, who refused surgery
* A solitary HCC ≤ 7.0cm in diameter, or multiple HCC ≤ 3 lesions, each ≤ 3.0cm in diameter
* Lesions being visible on ultrasound (US) and with an acceptable/safe path between the lesion and the skin as shown on US
* No extrahepatic metastasis
* No imaging evidence of invasion into the major portal/hepatic vein branches
* No history of encephalopathy, ascites refractory to diuretics or variceal bleeding
* A platelet count of \> 40,000/mm3
* No previous treatment of HCC except liver resection

Exclusion Criteria:

* Patient compliance is poor
* The blood supply of tumor lesions is absolutely poor or arterial-venous shunt that TACE can not be performed
* Previous or concurrent cancer that is distinct in primary site or histology from HCC, EXCEPT cervical carcinoma in situ, treated basal cell carcinoma, superficial bladder tumors (Ta, Tis \& T1). Any cancer curatively treated \> 3 years prior to entry is permitted.
* History of cardiac disease:

  * Congestive heart failure \> New York Heart Association (NYHA) class 2
  * Active coronary artery disease (myocardial infarction more than 6 months prior to study entry is permitted)
  * Cardiac arrhythmias requiring anti-arrhythmic therapy other than beta blockers, calcium channel blocker or digoxin; or
  * Uncontrolled hypertension (failure of diastolic blood pressure to fall below 90 mmHg, despite the use of 3 antihypertensive drugs).
* Active clinically serious infections (\> grade 2 National Cancer Institute \[NCI\]-Common Terminology Criteria for Adverse Events \[CTCAE\] version 3.0)
* Known history of human immunodeficiency virus (HIV) infection
* Known central nervous system tumors including metastatic brain disease
* Patients with clinically significant gastrointestinal bleeding within 30 days prior to study entry
* Distantly extrahepatic metastasis
* History of organ allograft
* Substance abuse, medical, psychological or social conditions that may interfere with the patient's participation in the study or evaluation of the study results
* Known or suspected allergy to the investigational agent or any agent given in association with this trial
* Any condition that is unstable or which could jeopardize the safety of the patient and his/her compliance in the study
* Pregnant or breast-feeding patients. Women of childbearing potential must have a negative pregnancy test performed within seven days prior to the start of study drug. Both men and women enrolled in this trial must use adequate barrier birth control measures during the course of the trial.
* Excluded therapies and medications, previous and concomitant:

  * Prior use of any systemic anti-cancer treatment for HCC, eg. chemotherapy, immunotherapy or hormonal therapy (except that hormonal therapy for supportive care is permitted). Antiviral treatment is allowed, however interferon therapy must be stopped at least 4 weeks prior randomization.
  * Prior use of systemic investigational agents for HCC
  * Autologous bone marrow transplant or stem cell rescue within four months of start of study drug

Primary outcomes:
measure: Overall Survival
timeFrame: 3, 5 years
Secondary outcomes:
measure: Recurrence rates
timeFrame: 3, 5-years
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: Department of Hepatobilliary Surgery, Cancer Center, Sun Yat-sen University
state: Guangdong
Study officials:
affiliation: Department of Hepatobilliary Surgery, Cancer Center, Sun Yat-sen University
name: Min-Shan Chen, Doctor
role: PRINCIPAL_INVESTIGATOR
affiliation: Department of Hepatobilliary Surgery, Cancer Center, Sun Yat-sen University
name: Jin-Qing Li, Doctor
role: STUDY_CHAIR
References:
citation: Bruix J, Sherman M; Practice Guidelines Committee, American Association for the Study of Liver Diseases. Management of hepatocellular carcinoma. Hepatology. 2005 Nov;42(5):1208-36. doi: 10.1002/hep.20933. No abstract available.
citation: Peng ZW, Zhang YJ, Chen MS, Xu L, Liang HH, Lin XJ, Guo RP, Zhang YQ, Lau WY. Radiofrequency ablation with or without transcatheter arterial chemoembolization in the treatment of hepatocellular carcinoma: a prospective randomized trial. J Clin Oncol. 2013 Feb 1;31(4):426-32. doi: 10.1200/JCO.2012.42.9936. Epub 2012 Dec 26.