Stereotactic Body Radiation Therapy for Hepatocellular Carcinoma

Phase II Multicenter Study of Stereotactic Body Radiation Therapy for Hepatocellular Carcinoma: Toxicity and Outcome

The standard treatment for hepatocellular carcinoma (HCC) is surgery, such as, by hepatic resection or liver transplantation, but less than 20% of HCC patients are suitable for surgery. In the remaining patients with inoperable and advanced HCC, trans-arterial chemo-embolization (TACE) has been widely used but TACE alone rarely produces complete response and commonly develops recurrence. Recently several small studies reported high tumor response and local control rate after stereotactic body radiotherapy (SBRT) alone or with TACE for inoperable HCC. A single institution phase II trial with SBRT for inoperable HCC after incomplete TACE at Korea Cancer Center Hospital showed promising results: the overall response rate of 73% and 2-year local control rate of 95%. They reported severe gastrointestinal toxicity of 11% because there was no normal tissue constraint for gastrointestinal tract and dosage to gastrointestinal tract was restricted to the lowest levels possible. In addition, they found that the presence of gastroduodenal ulcer before SBRT was significantly influenced on severe gastrointestinal toxicity. Based on this study, we will conduct a multicenter phase II trial on maintenance of treatment results and reduction of severe treatment related toxicity below 5%. To achieve this, we strictly apply normal tissue constraints. Secondly, we will do Esophagogastroduodenoscopy (EGD) before SBRT to evaluate gastroduodenal ulcer. After then, we will apply the normal tissue constraint of gastrointestinal tract according to gastroduodenal ulcer.

Study Overview

• Status: Completed
• Conditions: Hepatocellular Carcinoma
• Intervention / Treatment: Radiation: Stereotactic body radiotherapy

• Study Type: Interventional
• Enrollment (Actual): 74
• Phase: Phase 2

Contacts and Locations

Study Locations

• Korea, Republic of
  • Busan, Korea, Republic of, 612-896
    • INJE University Haeundae Paik Hospital
  • Busan, Korea, Republic of
    • Dongnam Institute of Radiological & Medical Sciences
  • Cheonan, Korea, Republic of
    • Soon Chun Hyang University Hospital Cheonan
  • Incheon, Korea, Republic of
    • Inha University Hospital
  • Incheon, Korea, Republic of
    • Catholic University Incheon St. Mary's Hospital
  • Seoul, Korea, Republic of
    • Soon Chun Hyang University Hospital Seoul
  • Seoul, Korea, Republic of, 139-706
    • Korea Cancer Center Hospital, Korea Institute of Radiological and Medical Sciences

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male or female patients ≥ 20 years of age
• Initially diagnosed or recurrent hepatocellular carcinoma (HCC)
• Unresectable HCC
• Inaccessible to local ablative treatment
• Cirrhotic status of Child Pugh class A or B7
• Eastern Cooperative Oncology Group performance status 0 or 1
• Tumor size < 10cm
• The volume of uninvolved must be at least 700 ml
• Incomplete response after trans-arterial chemo-embolization of 1-5
• A single lesion or multiple lesions including portal vein tumor thrombosis included in radiation field with one or consecutive sessions of SBRT
• No evidence of an uncontrolled lesion at any other site
• No evidence of complications of liver cirrhosis
• No evidence of uncontrolled inter-current illness
• Patient or guardian must be able to provide verbal and written informed consent

Exclusion Criteria:

• Patient with previous history of abdominal radiation
• Direct invasion to esophagus, stomach or colon by HCC

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Stereotactic body radiotherapy; Stereotactic body radiotherapy for unresectable hepatocellular carcinoma after incomplete trans-arterial chemo-embolization

Radiation: Stereotactic body radiotherapy; Total stereotactic Body radiotherapy (SBRT) doses will be 60 Gy in 3 fractionations. Patients receive 3 fractionations separated by >48 hours. At least 700 ml of normal liver (entire liver minus cumulative GTV) should not receive a total dose of > 17 Gy in three fractions. If volume of normal liver does not exceed 700 ml, at least 70% of normal liver should not receive a total dose of > 17 Gy. In patients without gastroduodenal ulcer on Esophagogastroduodenoscopy (EGD) before SBRT, D2ml of gastrointestinal tract should not exceed 35 Gy. In patients with gastroduodenal ulcer on EGD before SBRT, D2ml of gastrointestinal tract should exceed 28 Gy. (D2ml: minimum dose to 2 ml of gastrointestinal tract); Other Names: Stereotactic ablative radiotherapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Treatment related toxicity-free survival	From the date of SBRT to the date of treatment related toxicity or last follow-up; Treatment related toxicity will be evaluated by the following criteria.; Adverse events using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0;; Classic radiation induced liver disease;; Non-classic Classic radiation induced liver disease;; Worsening of Child-Turcotte-Pugh score;; Worsening of MELD score	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival	From the date of SBRT to the date of death or last follow-up	2 years
Progression free survival	From the date of SBRT to the date of first failure or last follow-up	2 years
Intrahepatic recurrence free survival	From the date of SBRT to the date of Intrahepatic recurrence or last follow-up	2 years
Patterns of failure	Patterns of failure (local, intrahepatic, or systemic)	2 years
Systemic failure free survival	From the date of SBRT to the date of systemin failure or last follow-up	2 years
Local control rate	From the date of SBRT to the date of local failure or last follow-up	2 years

Collaborators and Investigators

• Sponsor: Korea Cancer Center Hospital
• Collaborators: Inje University; Soonchunhyang University Hospital; Incheon St.Mary's Hospital; Inha University Hospital; Dongnam Institute of Radiological & Medical Sciences

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2012
• Primary Completion (Actual): April 1, 2015
• Study Completion (Actual): September 1, 2017

Study Registration Dates

• First Submitted: May 7, 2013
• First Submitted That Met QC Criteria: May 8, 2013
• First Posted (Estimate): May 9, 2013

Study Record Updates

• Last Update Posted (Actual): September 20, 2019
• Last Update Submitted That Met QC Criteria: September 18, 2019
• Last Verified: September 1, 2019

More Information

Terms related to this study

• Keywords: Hepatocellular carcinoma; Stereotactic body radiotherapy; Stereotactic ablative radiotherapy
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Digestive System Neoplasms; Liver Diseases; Liver Neoplasms; Carcinoma; Carcinoma, Hepatocellular
• Other Study ID Numbers: K-1201-001-004 (Other Identifier: [Registry ID: Clinical Research information Service); KCT0000454 (Registry Identifier: Clinical Research Information Service)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED