A Study of Comparison of TACE Combination With and Without EBRT for Advanced HCC (TACE-EBRT)

A Prospective, Randomized, Multicenter Study of Comparison of TACE Combination With and Without EBRT for HCC Which is Unresectable But Confined to the Liver

This clinical trial is a prospective, randomized, controlled and multicenter study.And the trial is going to better control intrahepatic tumors for hepatocellular carcinoma(HCC) patients who meet the inclusion criterion.The patients were divided into two groups, the group A by TACE and the other group B by external- beam radiotherapy(EBRT) after 2 times TACE. Then the therapeutic effects and toxicities of TACE and EBRT are evaluated during the follow-up period. The study design plans to enroll 300 patients, and each group includes 150 cases.

Study Overview

• Status: Unknown
• Conditions: Hepatocellular Carcinoma
• Intervention / Treatment: Procedure: Transcatheter arterial chemoembolization; Radiation: External- beam radiotherapy

Detailed Description

Enrolled HCC patients met the inclusion criterion, in the late or advanced stage,tumor confined in intrahepatic( meet the tolerance-dose for the liver), without cancer embolus in main branch of portal vein, without extrahepatic metastasis and the number of tumor was≤3. Eligible participants will be randomly assigned to the group A by TACE and the other group B by EBRT after 2 times TACE.

TACE group: The frequency of treatment is determined based on the disease condition for patients who are randomly assigned to group of TACE.TACE is performed via an injection into the hepatic artery of agents by puncturing the common femoral artery, and micro-embolization superselective catheterization is preferred.Adriamycin(30 to 60mg) is considered as basic chemotherapy drugs in the process of transcatheter endovascular perfusion.The dose of fluid lipiodol was determined by diameter and blood supply type of HCC,generally 5-20ml, and no more than 30ml once.The boundary is considered whether there are large amounts of lipiodol to deposit in the tumor and tiny branches shadow of portal veins in paracarcinoma under fluoroscopic guidance. Embolizing agents(gelatin sponge particles 350um-560um) are added after lipiodol emulsion embolization.It has a possibility of observeation alone if tumor achieves a complete response after two times TACE.

EBRT group: Patients who were randomized to the radiotherapy group start radiotherapy 3-5 weeks after the completion 2 times TACE and began to undergo radiation. Radiotherapy equipment is based on the conditions of the cooperative units. 3-dimensional conformal radiation therapy(3-DCRT), intensity-modulated radiation therapy(IMRT) or Image-Guided Radiotherapy(IGRT) will be opted based on hospital. IGRT can also be used via helical tomotherapy, Rapid Arc or Volumetric Modulated Arc Therapy(VMAT). The target volume should include the visible tumor.

• Study Type: Interventional
• Enrollment (Anticipated): 300
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200032
      • Recruiting
      • 180 Fenglin Road
      • Contact: Yixing Chen, Phd; Phone Number: 86-13916056575; Email: chen.yixing@zs-hospital.sh.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

1. Inclusion Criteria 1）initially diagnosed HCC (confirmed by pathology or meet clinical diagnostic criteria), 2）The patients are not candidates for curative surgery, which should be determined in consultation with two oncology surgeons of the same center, 3）Tumor was confined in intrahepatic( meet the tolerance-dose for the liver), without cancer embolus in main branch of portal vein, without extrahepatic metastasis and the number of tumor was≤3, 4）Child-Pugh A，white blood cell count >2*109/L、Hb>90g/L、PLT>50*109/L, 5）The score of Eastern Cooperative Oncology Group(ECOG): 0-2, 6）The estimated survival time > 3 months, 7）Without midsection history of radiation therapy, 8）Age: >18 years old, 9）Informed consent was signed.
2. Exclusion Criteria 1）Diffuse hepatocellular carcinoma, 2）Uncontrollable infection, 3）Concurrent other malignant tumors, 4）Simultaneously participate in other experimental drugs or clinical trials, 5）Serious of heart, lung and kidney diseases, 6）During pregnancy and lactation, 7) The ones with severe neurologic morbidity couldn't clearly tell therapeutic response.
3. Halfway exit criteria 1）Do not treat according to the research or seriously violate the fundamental principles after enrolled, 2）Cannot tolerate radiation therapy, including the ones that cann't complete the radiation treatment( the dose <40 Gy,biological effective dose <48 Gy), or interrupt more than 2 weeks during radiotherapy, 3）Unwilling to continue this clinical trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: SINGLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Transcatheter arterial chemoembolization; TACE group: The frequency of treatment is determined based on the disease condition for patients who are randomly assigned to group of TACE treatment.TACE is performed via an injection into the hepatic artery of agents by puncturing the common femoral artery, and micro-embolization superselective catheterization is preferred.Adriamycin(30 to 60mg) is considered as basic chemotherapy drugs in the process of transcatheter endovascular perfusion.The dose of ultra fluid lipiodol was determined by diameter and blood supply type of HCC,generally 5-20ml, and no more than 30ml once.The boundary is considered whether there are large amounts of lipiodol to deposit in the tumor and tiny branches shadow of portal veins in paracarcinoma under fluoroscopic guidance. Embolizing agents(gelatin sponge particles 350um-560um) are added after lipiodol emulsion embolization.It has a possibility of observeation alone if tumor achieves a complete response after two times TACE.	Procedure: Transcatheter arterial chemoembolization; Transcatheter arterial chemoembolization (TACE) is performed via an injection into the hepatic artery of agents by puncturing the common femoral artery.Adriamycin(30 to 60 mg) is considered as basic chemotherapy drugs in the process of transcatheter endovascular perfusion. The dose of lipiodol was determined by diameter and blood supply type of HCC, generally 5-20ml, and no more than 30ml once.; Other Names: TACE
EXPERIMENTAL: External-beam radiotherapy; EBRT group: Patients who were randomized to the external- beam radiotherapy (EBRT) 3-5 weeks after the completion 2 times TACE.Radiotherapy equipment is based on the conditions of the cooperative units. 3-DCRT, IMRT or IGRT will be opted based on hospital. IGRT can also be used via helical tomotherapy, Rapid Arc or VMAT. The target volume should include the visible tumor.	Radiation: External- beam radiotherapy; We have reported a series of retrospective clinical trials in which transarterial chemoembolization (TACE) combined with external- beam radiotherapy (EBRT) was a better treatment method than TACE alone for unresectable HCC in the same period and organization, no matter in aspects of the regression rate of carcinoma or survival.Patients who were randomized to the EBRT 3-5 weeks after the completion 2 times TACE.; Other Names: EBRT

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
3-year overall survival(OS)	The therapeutic effects are mainly evaluated by the 3-year overall survival(OS).	The outcome measures are assessed up to three years.

Collaborators and Investigators

• Sponsor: Shanghai Zhongshan Hospital
• Collaborators: Peking University First Hospital; Changhai Hospital; Zhongshan Hospital Xiamen University; Fudan University; Fujian Cancer Hospital; Chinese PLA General Hospital; First Affiliated Hospital, Sun Yat-Sen University; West China Hospital; Peking University Cancer Hospital & Institute; First Affiliated Hospital of Fujian Medical University; Qingdao University; Shanghai 10th People's Hospital; Nanfang Hospital of Southern Medical University; The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School; First Affiliated Hospital of Zhejiang University; Shandong Cancer Hospital and Institute; Fujian Medical University Union Hospital; Xinqiao Hospital of Chongqing; The Second Affiliated Hospital of Chongqing Medical University; First Affiliated Hospital of Xinjiang Medical University; 309th Hospital of Chinese People's Liberation Army; Anhui Provincial Hospital; Sichuan Cancer Hospital and Research Institute; Yunnan Cancer Hospital; The Affiliated Zhongshan Hospital of Dalian University; Jilin University; First Affiliated Hospital of Guangxi Medical University; Heilongjiang Provincial Agricultural Reclamation General Hospital; Longyan First Hospital, Affiliated to Fujian Medical University; The Third Affiliated Hospital of Qiqihar Medical Universitiy; The 4th people's hospital of Wuxi City, Affiliated to Jiangnan University; Subei People's Hospital of Jiangsu Province,Yangzhou University; Shanghai East Hospital,Tongji University School of Medicine; The 4th People's Hospital of Linfen City; The People's Hospital of Hunan Province
• Investigators: Study Director: Zhongshan Hospital, Fudan University, Shanghai, China

Study record dates

Study Major Dates

• Study Start (ACTUAL): January 1, 2017
• Primary Completion (ANTICIPATED): December 30, 2020
• Study Completion (ANTICIPATED): December 31, 2020

Study Registration Dates

• First Submitted: March 1, 2017
• First Submitted That Met QC Criteria: April 11, 2017
• First Posted (ACTUAL): April 17, 2017

Study Record Updates

• Last Update Posted (ACTUAL): April 10, 2020
• Last Update Submitted That Met QC Criteria: April 8, 2020
• Last Verified: April 1, 2020

More Information

Terms related to this study

• Keywords: Hepatocellular Carcinoma; external- beam radiotherapy (EBRT); transarterial chemoembolization (TACE)
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Digestive System Neoplasms; Liver Diseases; Liver Neoplasms; Carcinoma, Hepatocellular
• Other Study ID Numbers: ZS-TACE-EBRT-2017; 2016ZSLC20 (OTHER_GRANT: Zhongshan Hospital, Fudan University)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No