Microwave Ablation Combined With TACE in the Treatment of Unresectable Huge Hepatocellular Carcinoma Huge

Hepatocellular Carcinoma Non-resectable Clinical Trial

Official title:

Effectivity and Safety of Microwave Ablation Combined With Transcatheter Arterial Chemoembolization(TACE) for Huge Unresectable Hepatocellular Carcinoma: a Multicenter Analysis

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03277716
• Other study ID #: sysucc01
• Status: Recruiting
• Phase: N/A
• Start date: December 1, 2017
• Est. completion date: December 30, 2021

Study information

• Verified date: May 2019
• Source: Sun Yat-sen University
• Contact: Weijun Fan, M.D.
• Phone: +86-020-87343272
• Email: fanweijun1964[@]126.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study was to prospectively evaluate the efficacy and safety of TACE combined with MWA in patients with huge unresectable hepatocellular carcinoma.

Description:

Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide. Despite the widespread application of surveillance programs in high-risk populations, patients continue to present with huge (≥ 10 cm) HCCs.And it's still a challenge to treat huge HCC nowadays.Surgical resection is currently the only curative treatment for huge HCCs ; however, only a minority of patients are candidates for curative resection. Sorafenib is recommended for the treatment of advanced HCCs, including huge HCCs, but the usage is severely limited by high adverse event rates and low efficiency. Thus, transarterial chemoembolization (TACE) is considered the first choice for huge unresectable HCCs. Several studies have concluded that TACE effectively improves the overall survival of patients with huge HCCs. Meanwhile, microwave ablation (MWA) now has been shown to be safe and effective for local tumor control in HCC patients. However, neither MWA nor TACE alone can achieve complete control of large HCCs . Therefore, the combination of TACE and MWA (TACE+MWA) is an appealing approach to treat HCCs. TACE+MWA now has been shown to improve overall survival rates compared with TACE alone in patients with small to large HCCs. But little data is available on TACE+MWA in patients with huge unresectable HCCs. Thus, the study was designed.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 100
• Est. completion date: December 30, 2021
• Est. primary completion date: December 30, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

1. The performance status of Eastern Cooperative Oncology Group (ECOG) must be 0-1

2. The diagnosis of primary hepatocellular carcinoma must be in line with the American Society for the study of liver diseases (AASLD) diagnostic criteria for hepatocellular carcinoma (HCC)

3. Child-Pugh score A or B;

4. Aged from 18 to 75 years;

5. Subjects voluntarily join the study, and signe informed consent;

6. No anti-tumor therapy was received;

7. Meet the following 4 characteristics: A. primary tumor diameter more than or equal to 10cm; B. no more than 3 HCC foci, and the maximum diameter is less than or equal to 5cm; C. with IIa, I or no portal vein tumor thrombus (Cheng's Classification);D. the tumor could not be surgically removed

8. No extrahepatic metastases

Exclusion Criteria:

1. Abnormal coagulation function: PLT < 40×109/L, PTA < 40%;

2. Patients have the past history of liver cancer treatment, such as transplantation, resection, radiotherapy, chemotherapy and so on;

3. Patients participated in clinical trials of equipment or drugs (signed informed consent) within 4 weeks;

4. Patients accompany by ascites, hepatic encephalopathy and esophageal and gastric varices bleeding;

5. Any serious accompanying disease, which is expected to have an unknown, impact on the prognosis, include heart disease, inadequately controlled diabetes and psychiatric disorders;

6. Patients accompanied with other tumors or past medical history of malignancy;

7. Pregnant or lactating patients, all patients participating in this trial must adopt appropriate birth control measures during treatment;

8. Allergic to adriamycin chemotherapy drugs,contrast agent and lipiodol;

9. Patients have poor compliance.

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Hepatocellular
• Hepatocellular Carcinoma Non-resectable
• Microwave Ablation
• Transarterial Chemoembolization

Intervention

Procedure:
• TACE
TACE: With the patient under local anesthesia, a 5F French catheter was introduced into the abdominal aorta via the femoral artery using the Seldinger technique. Hepatic arterial angiography was performed using fluoroscopy to guide the catheter into the celiac and superior mesenteric arteries. Then, the feeding arteries, tumor, and vascular anatomy surrounding the tumor were identified. Subsequently, a microcatheter was super-selectively inserted into the feeding arteries. Then, a mixture solution containing chemotherapeutic agents and embolic agents were infused into the artery according to the size and blood supply of the tumors.
• MWA
MWA: All patients were instructed to fast from all foods for 12 hours preoperatively. During the procedure, a CT scan was used to locate the liver tumors, and to design the optimal puncture needle route. Routine disinfection and local anesthesia was applied around the puncture point, and a 16-gauge microwave antenna was gradually inserted into the tumor along the pre-determined angle. Settings of the MWA parameters depended on the manufacturer's recommendation and our experience.

Device:
• MWA system
MWA system is a kind of medical treatment instrument to restrain and kill tumor based on microwave heating technique and biology heating effect theory.

Drug:
• Chemoembolization
Chemotherapeutic drugs: adriamycin,epirubicin and pirarubicin. Embolic agent: lipiodol and embolic microspherea The mixture solution containing chemotherapeutic drugs and embolic agent were infused into the artery according to by the number and size of the lesions, liver and kidney function of the patient, and blood supply of the tumors.

Locations

Country	Name	City	State
China	Cancer Institute &Hospital, Chinese Academy of Medical Sciences	Beijing	Beijing
China	The First Affiliated Hospital of Fujian Medical University	Fuzhou	Fujian
China	The tumor hospital of Fujian Province	Fuzhou	Fujian
China	the First Affiliated Hospital of SunYat-senUniversity	Guangzhou	Guangdong
China	The First Affiliated Hospital of Zhejiang University	Hangzhou	Zhejiang
China	Shandong Province Hospital	Jinan	Shandong
China	The Second Affiliated Hospital of Shandong University	Jinan	Shandong
China	the Affiliated Hospital of Medical College Qingdao University	Qingdao	Shandong
China	Peking University Hospital of Shenzhen	Shenzhen	Guangdong
China	Shenzhen People's Hospital	Shenzhen	Guangdong

Sponsors (1)

Lead Sponsor	Collaborator
Fan Weijun

Country where clinical trial is conducted

China, 

References & Publications (18)

Abdelaziz AO, Nabeel MM, Elbaz TM, Shousha HI, Hassan EM, Mahmoud SH, Rashed NA, Ibrahim MM, Abdelmaksoud AH. Microwave ablation versus transarterial chemoembolization in large hepatocellular carcinoma: prospective analysis. Scand J Gastroenterol. 2015 Apr;50(4):479-84. doi: 10.3109/00365521.2014.1003397. Epub 2015 Jan 16. — View Citation

Bruix J, Sherman M; American Association for the Study of Liver Diseases. Management of hepatocellular carcinoma: an update. Hepatology. 2011 Mar;53(3):1020-2. doi: 10.1002/hep.24199. — View Citation

Brunocilla PR, Brunello F, Carucci P, Gaia S, Rolle E, Cantamessa A, Castiglione A, Ciccone G, Rizzetto M. Sorafenib in hepatocellular carcinoma: prospective study on adverse events, quality of life, and related feasibility under daily conditions. Med Oncol. 2013 Mar;30(1):345. doi: 10.1007/s12032-012-0345-2. Epub 2012 Dec 22. — View 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. — View Citation

Feng K, Yan J, Li X, Xia F, Ma K, Wang S, Bie P, Dong J. A randomized controlled trial of radiofrequency ablation and surgical resection in the treatment of small hepatocellular carcinoma. J Hepatol. 2012 Oct;57(4):794-802. doi: 10.1016/j.jhep.2012.05.007. Epub 2012 May 23. — View Citation

Huang YH, Wu JC, Chen SC, Chen CH, Chiang JH, Huo TI, Lee PC, Chang FY, Lee SD. Survival benefit of transcatheter arterial chemoembolization in patients with hepatocellular carcinoma larger than 10 cm in diameter. Aliment Pharmacol Ther. 2006 Jan 1;23(1):129-35. — View Citation

Kim JH, Won HJ, Shin YM, Kim SH, Yoon HK, Sung KB, Kim PN. Medium-sized (3.1-5.0 cm) hepatocellular carcinoma: transarterial chemoembolization plus radiofrequency ablation versus radiofrequency ablation alone. Ann Surg Oncol. 2011 Jun;18(6):1624-9. doi: 10.1245/s10434-011-1673-8. Epub 2011 Mar 29. — View Citation

Kim JW, Shin SS, Kim JK, Choi SK, Heo SH, Lim HS, Hur YH, Cho CK, Jeong YY, Kang HK. Radiofrequency ablation combined with transcatheter arterial chemoembolization for the treatment of single hepatocellular carcinoma of 2 to 5 cm in diameter: comparison with surgical resection. Korean J Radiol. 2013 Jul-Aug;14(4):626-35. doi: 10.3348/kjr.2013.14.4.626. Epub 2013 Jul 17. — View Citation

Kim YS, Lim HK, Rhim H, Lee MW, Choi D, Lee WJ, Paik SW, Koh KC, Lee JH, Choi MS, Gwak GY, Yoo BC. Ten-year outcomes of percutaneous radiofrequency ablation as first-line therapy of early hepatocellular carcinoma: analysis of prognostic factors. J Hepatol. 2013 Jan;58(1):89-97. doi: 10.1016/j.jhep.2012.09.020. Epub 2012 Sep 27. — View Citation

Lü MD, Kuang M, Liang LJ, Xie XY, Peng BG, Liu GJ, Li DM, Lai JM, Li SQ. [Surgical resection versus percutaneous thermal ablation for early-stage hepatocellular carcinoma: a randomized clinical trial]. Zhonghua Yi Xue Za Zhi. 2006 Mar 28;86(12):801-5. Chinese. — View Citation

Maida M, Orlando E, Cammà C, Cabibbo G. Staging systems of hepatocellular carcinoma: a review of literature. World J Gastroenterol. 2014 Apr 21;20(15):4141-50. doi: 10.3748/wjg.v20.i15.4141. Review. — View Citation

Min YW, Lee JH, Gwak GY, Paik YH, Lee JH, Rhee PL, Koh KC, Paik SW, Yoo BC, Choi MS. Long-term survival after surgical resection for huge hepatocellular carcinoma: comparison with transarterial chemoembolization after propensity score matching. J Gastroenterol Hepatol. 2014 May;29(5):1043-8. doi: 10.1111/jgh.12504. — View Citation

Mizukoshi E, Yamashita T, Arai K, Sunagozaka H, Ueda T, Arihara F, Kagaya T, Yamashita T, Fushimi K, Kaneko S. Enhancement of tumor-associated antigen-specific T cell responses by radiofrequency ablation of hepatocellular carcinoma. Hepatology. 2013 Apr;57(4):1448-57. doi: 10.1002/hep.26153. — View 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. — View Citation

Shiina S, Tateishi R, Arano T, Uchino K, Enooku K, Nakagawa H, Asaoka Y, Sato T, Masuzaki R, Kondo Y, Goto T, Yoshida H, Omata M, Koike K. Radiofrequency ablation for hepatocellular carcinoma: 10-year outcome and prognostic factors. Am J Gastroenterol. 2012 Apr;107(4):569-77; quiz 578. doi: 10.1038/ajg.2011.425. Epub 2011 Dec 13. — View Citation

Xue T, Le F, Chen R, Xie X, Zhang L, Ge N, Chen Y, Wang Y, Zhang B, Ye S, Ren Z. Transarterial chemoembolization for huge hepatocellular carcinoma with diameter over ten centimeters: a large cohort study. Med Oncol. 2015 Mar;32(3):64. doi: 10.1007/s12032-015-0504-3. Epub 2015 Feb 15. — View Citation

Yamashita Y, Taketomi A, Shirabe K, Aishima S, Tsuijita E, Morita K, Kayashima H, Maehara Y. Outcomes of hepatic resection for huge hepatocellular carcinoma (= 10 cm in diameter). J Surg Oncol. 2011 Sep 1;104(3):292-8. doi: 10.1002/jso.21931. Epub 2011 Apr 4. — View Citation

Zerbini A, Pilli M, Penna A, Pelosi G, Schianchi C, Molinari A, Schivazappa S, Zibera C, Fagnoni FF, Ferrari C, Missale G. Radiofrequency thermal ablation of hepatocellular carcinoma liver nodules can activate and enhance tumor-specific T-cell responses. Cancer Res. 2006 Jan 15;66(2):1139-46. — View Citation

* Note: There are 18 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall survival (OS)	Overall survival (OS) will be defined as the elapsed time from the enrollment to death from any cause. For surviving patients, follow-up will be censored at the date of last contact (or last date known to be alive). Follow-up for OS will occur every 12 weeks (±1 month) until death or withdrawal of consent from the study.	up to 3 years
Secondary	Progression-free survival (PFS)	Progression-free survival (PFS) will be defined as the elapsed time from the first date of study treatment until documented disease progression (as per mRECIST) or death from any cause, whichever is earlier. For patients who remain alive without progression, follow-up time will be censored at the date of last disease assessment.	up to 3 years
Secondary	Adverse event rate	Adverse event rate will be defined as the rate of patients who developed adverse event.	up to 3 years
Secondary	Distant metastasis-free survival	Progression-free survival (PFS) will be defined as the elapsed time from the first date of study treatment until documented distant metastasis (as per RECIST 1.1) or death from any cause, whichever is earlier. For patients who remain alive without progression, follow-up time will be censored at the date of last disease assessment .	up to 3 years