Radiofrequency Ablation Accompanied With Spontaneous Sorafenib in Early to Intermediate Stage HCC

HCC Clinical Trial

Official title:

Radiofrequency Ablation Accompanied With Spontaneous Sorafenib Administration in the Treatment of Early to Intermediate Stage Hepatocellular Carcinoma: a Prospective Multicenter Cohort Study.(REASSESS)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02187081
• Other study ID #: SWHB008
• Status: Recruiting
• Phase: N/A
• First received: July 1, 2014
• Last updated: March 27, 2017
• Start date: March 15, 2017
• Est. completion date: December 2018

Study information

• Verified date: March 2017
• Source: Southwest Hospital, China
• Contact: Xiaobin Feng, Docter
• Phone: 86-23-68765297
• Email: fengxiaobin200708[@]aliyun.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Radiofrequency ablation (RFA)can be curative with small localized HCCs up to 5 cm in diameter. However, the long-term prognosis is not satisfactory due to the high incidence of recurrence.Multimodality treatments are needed to prevent recurrences，but only useful with locoregional disease. Sorafenib is an oral multi-kinase inhibitor and the only systemic drug associated with improved overall survival (OS) in patients with advanced HCC. Retrospective and randomized studies have suggested that the combined use of Sorafenib may be useful in patients with unresectable HCC. Based on these information and the multiple actions of Sorafenib, we hypothesized that Sorafenib plus RFA may be useful in patients with early to Mid term HCC. In this investigation, we evaluated the safety and efficacy of a combination Sorafenib and RFA therapy in patients with Barcelona Clinic Liver Cancer (BCLC) Stage 0 -B1 HCC in a multicenter prospective cohort study.

Description:

Radiofrequency ablation (RFA) has been used as a minimally invasive option to eradicate tumors and preserve liver function in patients with impaired function or with a postoperative tumor recurrence. RFA can be curative with small localized HCCs up to 5 cm in diameter. However, the long-term prognosis for HCC patients treated with RFA is not satisfactory due to the high incidence of recurrence including local tumor recurrence and multicentric carcinogenesis.

Multimodality treatments are needed to prevent recurrences. Although there is a potential benefit with this strategy, it is only useful with locoregional disease. Sorafenib is an oral multi-kinase inhibitor and the only systemic drug associated with improved overall survival (OS) in patients with advanced HCC.

Retrospective and randomized studies have suggested that the combined use of Sorafenib, TACE, and RFA may be useful in patients with unresectable HCC. Based on these information and the multiple actions of Sorafenib, we hypothesized that Sorafenib plus RFA may be useful in patients with early HCC or recurrent HCC. Although no supportive data from clinical trials is available, this hypothesis is supported by recent animal studies. Inadequate RFA has been shown to promote rapid progression of residual tumors. Adjuvant Sorafenib postponed time to recurrence by inhibition of hypoxia inducible factor-1and vascular endothelial growth factor A (VEGFA). In a multifocal tumor model of HCC, RFA and Sorafenib alone resulted in a significant volume reduction of non-RFA-targeted tumors, but this effect was enhanced when both modalities were combined. This phenomenon was also demonstrated by more recent study on human subject.

Besides the advantages, Sorafenib initially promoted necrosis, delayed tissue repair after RFA and adversely affected normal liver parenchyma, which could result in increased RFA toxicity and limit its use in patients with HCC who have undergone RFA. Thus, the overall advantages of RFA plus Sorafenib need to be weighed against its adverse effects. In this investigation, we evaluated the safety and efficacy of a combination Sorafenib and RFA therapy in patients with Barcelona Clinic Liver Cancer (BCLC) Stage 0 -B1 HCC in a multicenter prospective cohort study.

Outcome measures: Post-RFA tumor recurrence

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 380
• Est. completion date: December 2018
• Est. primary completion date: December 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

• Authorization of Informed Consent

• HCC diagnosed by biopsy or Image findings

• BCLC stage 0 to B1

• This time was the primary treatment of HCC. Had no history of any tumor specific therapy,including RFA,Hepatectomy,TACE,HIFU,and Transplantation

• Child Pugh A or B

• ECOG 0 to 2

• single lesion less than or equal to 5 cm,2 to 3 nodules, maximal size less than equal to 3cm

• Male or female (without pregnancy)

• Ages between 18 to 70 years

• Capable of take medicines

• anticipate at least survival of 12 weeks

• Unwilling to receive surgical resection or liver transplantation

• Potentially curable disease by RFA

• Sorafenib administrated less than 4 weeks before or after RFA procedures

• For any excuse,subject should take Sorafenib at least for 4 weeks

Exclusion Criteria:

• A cancer embolus in major hepatic vessels or extrahepatic metastases

• Tumor number more than 4 or tumor size larger than 5 cm

• A present or past history of uncontrollable ascites, hepatic encephalopathy or variceal bleeding

• A history of a secondary malignancy

• Severe dysfunction of the heart, kidney or other organs

• Active infection except viral hepatitis

• Any treatment history of target lesion including chemotherapy and TACE

• Pregnancy

• received other trials on gene therapy

• have received operation less than 4 weeks

Related Conditions & MeSH terms

• HCC

Intervention

Procedure:
• radiofrequency ablation plus Sorafenib
To treat HCC with the combination of radiofrequency ablation and sorafenib
• Radiofrequency ablation
To treat HCC with radiofrequency ablation alone.

Locations

Country	Name	City	State
China	Southwest Hospital	Chongqing	Chongqing

Sponsors (1)

Lead Sponsor	Collaborator
Southwest Hospital, China

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	2-year incidence of tumor recurrence	to calculate the incidence of tumor recurrence of experiment and control group at two year after complete treatment.	2 year
Secondary	Overall survival	Overall survival	5 years
Secondary	1-year incidence of recurrence	1-year incidence of recurrence	1-year
Secondary	3-year incidence of recurrence	3-year incidence of recurrence	3 year
Secondary	5-year incidence of recurrence	5-year incidence of recurrence	5 year
Secondary	Time to progression	Time to progression	average 2 years
Secondary	Disease Control Rate	Disease Control Rate	average 2 years
Secondary	complications and adverse effect	to sum all the complications and adverse effect for all the eligible enrolled patients during 1 year of a complete treatment.	1 year