Clinical trial NCT00556803: TACE as an Adjuvant Therapy After Radiofrequency Ablation (RFA) for Hepatocellular Carcinoma
Official title: Transcatheter Arterial Chemoembolization as an Adjuvant Therapy After Radiofrequency Ablation for Hepatocellular Carcinoma
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Hepatocellular Carcinoma
Liver Cancer
Keywords: hepatocellular carcinoma
liver cancer
radiofrequency ablation
transcatheter arterial chemoembolization
adjuvant therapy
Lead sponsor: Sun Yat-sen University
Sponsor class: OTHER
First posted: 2007-11-12
Enrollment: 120
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 transcatheter arterial chemoembolization (TACE) will improve the outcome of radiofrequency ablation for hepatocellular carcinoma (HCC) or not.

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 ≤ 5.0 cm, 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 5 cm is less favorable, and the local recurrence rate can be as high as 20% even in small HCC less than 3.5 cm. 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) has proven to be an effective and palliative therapy for unresectable HCC. And some prospective randomized controlled trials have shown that adjuvant TACE after curative resection for HCC can improve the overall survivals and decrease the recurrence rates. But there have not been any studies about TACE as an adjuvant therapy after RFA for HCC.

Thus, the purpose of this study is to prospectively evaluate whether TACE as an adjuvant therapy after RFA for HCC will improve the outcomes of RFA.

Eligibility criteria: Inclusion Criteria:

* Aged 18 - 75 years, and refused surgery
* A solitary HCC ≤ 7.0 cm in diameter, or multiple HCC ≤ 3 lesions, each ≤ 3.0 cm 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 so that TACE cannot 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 and 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
  * 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 to 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 survivals
timeFrame: 3, and 5-years
Secondary outcomes:
measure: Recurrence rates
timeFrame: 3, and 5-years
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: Department of Hepatobiliary Surgery, Cancer Center, Sun Yat-sen University
state: Guangdong
Study officials:
affiliation: Department of Hepatobiliary Surgery, Cancer Center, Sun Yat-sen University
name: Min-Shan Chen, M.D., Ph.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Poon RT, Fan ST, Tsang FH, Wong J. Locoregional therapies for hepatocellular carcinoma: a critical review from the surgeon's perspective. Ann Surg. 2002 Apr;235(4):466-86. doi: 10.1097/00000658-200204000-00004.
citation: Chen MS, Li JQ, Zheng Y, Guo RP, Liang HH, Zhang YQ, Lin XJ, Lau WY. A prospective randomized trial comparing percutaneous local ablative therapy and partial hepatectomy for small hepatocellular carcinoma. Ann Surg. 2006 Mar;243(3):321-8. doi: 10.1097/01.sla.0000201480.65519.b8.
citation: Buscarini L, Buscarini E, Di Stasi M, Vallisa D, Quaretti P, Rocca A. Percutaneous radiofrequency ablation of small hepatocellular carcinoma: long-term results. Eur Radiol. 2001;11(6):914-21. doi: 10.1007/s003300000659.