TACE Combined With Synchronous Radiofrequency /Microwave Ablation to Treat Large and Huge Hepatocellular Carcinoma

Carcinoma, Hepatocellular Clinical Trial

Official title:

Clinical Study of Transarterial Chemoembolization (TACE) Combined With Synchronous Radiofrequency /Microwave Ablation to Treat Large and Huge Hepatocellular Carcinoma

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02630108
• Other study ID #: B2015-146R
• Status: Recruiting
• Phase: Phase 3
• First received: December 3, 2015
• Last updated: October 17, 2016
• Start date: December 2015
• Est. completion date: April 2018

Study information

• Verified date: October 2016
• Source: Shanghai Zhongshan Hospital
• Contact: Jianhua Wang, MD
• Phone: +8613611759557
• Email: wang.jianhua[@]zs-hospital.sh.cn
• Is FDA regulated: No
• Health authority: China: Shanghai Municipal Commission of Health and Family Planning
• Study type: Interventional

Clinical Trial Summary

It is a prospective and multi-center clinical research in China to compare the efficacy, safety and related impact factors between TACE alone and TACE combined with synchronous multi-point MWA/RFA for large and huge liver cancer.

Description:

It is an open random prospective phase III clinical trial conducted by Principal Investigator Professor Jian-Hua Wang. Investigators in twenty-five hospitals in China participate in. Patients with unresectable large HCC (>5cm in diameter) and huge HCC (>=10cm in diameter) are enrolled. The investigators propose to recruitment 280 patients who are randomly assigned into the combined group (treated with TACE and synchronous ablation) and the control group (treated with TACE alone) according to the proportion of 1:1, which means 140 patients in each group. The criteria of inclusion and exclusion, and the methods of lab tests, imaging modality and treatment procedures are the same.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 280
• Est. completion date: April 2018
• Est. primary completion date: December 2017
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

1. Patients with primary liver cancer aged from 18-80 years, and life expectancy longer than three months;

2. Patients with large HCC (>5cm in diameter) and huge HCC (=10cm in diameter), including HCC and mixed type of liver cancer (HCC-ICC);

3. Patients with no thrombus in main portal vein (PV)

4. Patients' liver function classified as Child-Pugh A or B, ECOG PS = 2;

5. Patients without bleeding tendency or coagulation disorder, or with reversible coagulopathy after therapy;

6. White blood cell count = 3.0×10^9/L;

7. Hemoglobin = 8.5g/dl;

8. Platelet = 50×10^9/L;

9. INR = 2.3 or PT not exceeding the upper limit of reference 3 seconds;

10. Blood creatinine less than 1.5 times of upper limit of reference;

11. Patients and/or their relatives willing to join in the clinical trial and signing the informed consent.

Exclusion Criteria:

1. Patients with diffuse type of liver cancer;

2. Cholangiocellular carcinoma

3. Patients with main PV thrombus;

4. Patients with hepatic vein thrombus;

5. Patients with lymph node or distant metastasis outside of liver;

6. Patients' liver function classified as Child-Pugh C and no improvement after treatment of liver protection;

7. Patients with irreversible coagulation disorder and abnormality in blood routine test, or having obvious bleeding tendency;

8. Patients with intractable massive ascites;

9. Patients' ECOG PS >2;

10. Patients complicated with active infection, especially cholangitis;

11. Patients with severe disorders of heart, lungs, kidneys, or brain;

12. Patients and/or their relatives refuse to anticipate this study.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Hepatocellular

Intervention

Procedure:
• Thermal Ablation
Thermal ablation in this trial includes radiofrequency ablation and microwave ablation, one of them can be chosen to be performed.

Drug:
• EADM
EADM is a chemotherapy drug used in transarterial chemoembolization (TACE).Dosage: EADM 30-60 mg per patient,depending on the situation of the patient.
• Ultra-fluid lipiodol
Ultra-fluid lipiodol is a kind of embolization material used in TACE. Standard: 38% ultra-fluid lipiodol .

Other:
• Gelatin sponge articles
Gelatin sponge articles embolization material used in TACE. Standard: 350-560 um in diameter.

Locations

Country	Name	City	State
China	Department of Interventional Radiology, Zhongshan Hospital, Fudan University	Shanghai	Shanghai

Sponsors (25)

Lead Sponsor

Collaborator

Shanghai Zhongshan Hospital

Anhui Provincial Hospital, Changhai Hospital, Chinese PLA General Hospital, Dalian University affiliated Zhongshan Hospital, Eastern Hepatobiliary Surgery Hospital, First Affiliated Hospital of Xinjiang Medical University, Guangdong General Hospital, Henan Cancer Hospital, Hunan Provincial People's Hospital, Jiangsu Cancer Institute & Hospital, Jilin Provincial Tumor Hospital, Nanfang Hospital of Southern Medical University, Qilu Hospital, Shandong Tumor Hospital, Shanghai Cancer Hospital, China, Shengjing Hospital, Sichuan Cancer Hospital and Research Institute, Sun Yat-sen University, The First Affiliated Hospital of Anhui Medical University, The First Hospital of Lanzhou University, The Third Affiliated Hospital of Harbin Medical University, Wuhan Union Hospital, China, Xijing Hospital, Zhejiang Cancer Hospital

Country where clinical trial is conducted

China, 

References & Publications (30)

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Ding J, Jing X, Liu J, Wang Y, Wang F, Wang Y, Du Z. Complications of thermal ablation of hepatic tumours: comparison of radiofrequency and microwave ablative techniques. Clin Radiol. 2013 Jun;68(6):608-15. doi: 10.1016/j.crad.2012.12.008. Epub 2013 Feb 8 — View Citation

Dong BW, Zhang J, Liang P, Yu XL, Su L, Yu DJ, Ji XL, Yu G. Sequential pathological and immunologic analysis of percutaneous microwave coagulation therapy of hepatocellular carcinoma. Int J Hyperthermia. 2003 Mar-Apr;19(2):119-33. — View Citation

Forner A, Llovet JM, Bruix J. Hepatocellular carcinoma. Lancet. 2012 Mar 31;379(9822):1245-55. doi: 10.1016/S0140-6736(11)61347-0. Epub 2012 Feb 20. Review. — View Citation

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Koo JE, Kim JH, Lim YS, Park SJ, Won HJ, Sung KB, Suh DJ. Combination of transarterial chemoembolization and three-dimensional conformal radiotherapy for hepatocellular carcinoma with inferior vena cava tumor thrombus. Int J Radiat Oncol Biol Phys. 2010 S — View Citation

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Lencioni R, Llovet JM. Modified RECIST (mRECIST) assessment for hepatocellular carcinoma. Semin Liver Dis. 2010 Feb;30(1):52-60. doi: 10.1055/s-0030-1247132. Epub 2010 Feb 19. Review. — View Citation

Liang P, Wang Y, Yu X, Dong B. Malignant liver tumors: treatment with percutaneous microwave ablation--complications among cohort of 1136 patients. Radiology. 2009 Jun;251(3):933-40. doi: 10.1148/radiol.2513081740. Epub 2009 Mar 20. — View Citation

Liu C, Liang P, Liu F, Wang Y, Li X, Han Z, Liu C. MWA combined with TACE as a combined therapy for unresectable large-sized hepotocellular carcinoma. Int J Hyperthermia. 2011;27(7):654-62. doi: 10.3109/02656736.2011.605099. Epub 2011 Oct 3. — View Citation

Liu Y, Zheng Y, Li S, Li B, Zhang Y, Yuan Y. Percutaneous microwave ablation of larger hepatocellular carcinoma. Clin Radiol. 2013 Jan;68(1):21-6. doi: 10.1016/j.crad.2012.05.007. Epub 2012 Jul 4. — View Citation

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Llovet JM, Real MI, Montaña X, Planas R, Coll S, Aponte J, Ayuso C, Sala M, Muchart J, Solà R, Rodés J, Bruix J; Barcelona Liver Cancer Group. Arterial embolisation or chemoembolisation versus symptomatic treatment in patients with unresectable hepatocell — View Citation

Mabed M, Esmaeel M, El-Khodary T, Awad M, Amer T. A randomized controlled trial of transcatheter arterial chemoembolization with lipiodol, doxorubicin and cisplatin versus intravenous doxorubicin for patients with unresectable hepatocellular carcinoma. Eu — View Citation

Ni JY, Sun HL, Chen YT, Luo JH, Chen D, Jiang XY, Xu LF. Prognostic factors for survival after transarterial chemoembolization combined with microwave ablation for hepatocellular carcinoma. World J Gastroenterol. 2014 Dec 14;20(46):17483-90. doi: 10.3748/ — View Citation

Poggi G, Montagna B, DI Cesare P, Riva G, Bernardo G, Mazzucco M, Riccardi A. Microwave ablation of hepatocellular carcinoma using a new percutaneous device: preliminary results. Anticancer Res. 2013 Mar;33(3):1221-7. — View Citation

Qian GJ, Wang N, Shen Q, Sheng YH, Zhao JQ, Kuang M, Liu GJ, Wu MC. Efficacy of microwave versus radiofrequency ablation for treatment of small hepatocellular carcinoma: experimental and clinical studies. Eur Radiol. 2012 Sep;22(9):1983-90. doi: 10.1007/s — View Citation

Shiomi H, Naka S, Sato K, Demura K, Murakami K, Shimizu T, Morikawa S, Kurumi Y, Tani T. Thoracoscopy-assisted magnetic resonance guided microwave coagulation therapy for hepatic tumors. Am J Surg. 2008 Jun;195(6):854-60. doi: 10.1016/j.amjsurg.2007.08.05 — View Citation

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Takayasu K, Arii S, Kudo M, Ichida T, Matsui O, Izumi N, Matsuyama Y, Sakamoto M, Nakashima O, Ku Y, Kokudo N, Makuuchi M. Superselective transarterial chemoembolization for hepatocellular carcinoma. Validation of treatment algorithm proposed by Japanese — View Citation

Terzi E, Piscaglia F, Forlani L, Mosconi C, Renzulli M, Bolondi L, Golfieri R; BLOG-Bologna Liver Oncology Group, S.Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy. TACE performed in patients with a single nodule of hepatocellular carcinom — View Citation

Xu LF, Sun HL, Chen YT, Ni JY, Chen D, Luo JH, Zhou JX, Hu RM, Tan QY. Large primary hepatocellular carcinoma: transarterial chemoembolization monotherapy versus combined transarterial chemoembolization-percutaneous microwave coagulation therapy. J Gastro — View Citation

Yin XY, Xie XY, Lu MD, Xu HX, Xu ZF, Kuang M, Liu GJ, Liang JY, Lau WY. Percutaneous thermal ablation of medium and large hepatocellular carcinoma: long-term outcome and prognostic factors. Cancer. 2009 May 1;115(9):1914-23. doi: 10.1002/cncr.24196. — View Citation

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* Note: There are 30 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Survival		From the date of randomization until the date of death from any cause, assessed up to 26 months	No
Secondary	Time-to-Disease Progression	TTDP follow-up is done at three months interval after lesions defined as stable with treatment of TACE or ablation combined with synchronous TACE six months after enrollment until lesions are defined as disease progression.	From the date of first procedure of TACE or TACE combined with synchronous ablation until the time when the disease progresses from an intermediate to an advanced stage as defined by specific events, assessed up to 26 months	No
Secondary	Objective response rate (ORR)	The ratio of CR plus PR. The efficacy is defined as complete regression (CR), partial regression (PR), stable disease (SD) and progressive disease (PD) according to modified Response Evaluation Criteria in Solid Tumors (mRESIST)	Six months after the date of first procedure of TACE or TACE combined with synchronous ablation.	No
Secondary	Progression free survival(PFS)		From the date of first procedure of TACE or TACE combined with synchronous ablationto until the time when lesions are defined as disease progression or death by any cause,assessed up to 26 months.	No
Secondary	Numbers of TACE and TACE combined with ablation cycles	The times of the subjects undergoing TACE or TACE combined with ablation	From the date of randomization until the date of death, assessed up to 26 months.	No
Secondary	Number of participants with adverse events and severe adverse events in TACE alone and TACE combined with ablation groups	Serious or mild adverse events after treatment	From the date of randomization until the date of follow-up visit (30 days after the procedure of TACE or TACE combined with thermal ablation)	Yes

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