Trial record 1 of 1 for:    NCT 01910909
Previous Study | Return to List | Next Study

Stereotactic Body Radiotherapy for Unresectable Hepatocellular Carcinoma (SBRT for HCC)

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2013 by Samsung Medical Center
Sponsor:
Information provided by (Responsible Party):
Samsung Medical Center
ClinicalTrials.gov Identifier:
NCT01910909
First received: July 17, 2013
Last updated: January 13, 2014
Last verified: July 2013
  Purpose

1. Background 1.1. Hepatocellular carcinoma (HCC) HCC is the third most common cause of cancer death globally. It is also the second cause of cancer mortality in Korea, despite the incidence of HCC was fifth. The most important cause of this discrepancy is connected with the fact that the significant portion of the HCC is detected as unresectable status.

1.2. Standard treatment of the HCC At the point of HCC diagnosis, only 30% of the patients could receive standard curative treatment, like resection, liver transplantation, and radiofrequency ablation (RFA). Transcatheter arterial chemoembolization (TACE) has been shown in randomized trials to improve survival compared with symptomatic therapy alone, in the patients without macrovascular involvement, extrahepatic disease and tumor related symptoms. However, in the recent review of TACE, TACE might be contraindicate or not recommended in the patients who showed vascular tumor invasion, more than 10 cm size, poor portal blood flow and/or repeated poor response.

Recently, Sorafenib, which is one of the target agents, showed survival advantage on unresectable HCC patients in two randomized study. In those study, sorafenib improved approximately three month overall survival increment, however, the median survival duration was only 10.7 months in experiment group (received sorafenib), and even 6.5 months in Asian-Pacific trial. Additionally, the possibility that sorafenib effect could be reduced in the patients had hepatitis B virus (HBV) was suggested in the subgroup analysis.

1.3 Radiation therapy (RT) for the HCC The use of RT in HCC is increased with the radiation technological advances. In the unresectable patients, RT showed 50 to 60% response rate with the dose response relationship. Recently, stereotactic body radiation therapy (SBRT) showed excellent local control and comparable survival rate in thoracic tumor. In the HCC, SBRT also showed 75 to 100% local control rate without significant elevation of the toxicities. One study reported that 24 to 54 Gy SBRT achieved 87% 1year local control and 17 months overall survival. The standard treatment of unresectable HCC is sorafenib, but Korean Liver Cancer Study Group (KLCSG) recommend RT as an option in localized unresectable HCC. Furthermore, Radiation Therapy Oncology Group (RTOG) started randomized trial to confirm the effect of SBRT in unresectable HCC (RTOG 1112).

Investigators previously reported the retrospective result that the higher dose SBRT achieved 2 year overall survival 87.9% and local control 85% in the patient who showed less than 5 cm solitary HCC without portal vein involvement.

Based on those studies, we start this prospective study to evaluate the effectiveness and adverse event of SBRT in the patients who had solitary 3 cm or less size HCC without extrahepatic lesion and vascular involvement.


Condition Intervention Phase
Localized Non-Resectable Adult Hepatocellular Carcinoma
Radiation: Stereotactic body radiotherapy
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Effectiveness and Safety of the Stereotactic Body Radiation Therapy for Hepatocellular Carcinoma: Prospective Phase II Trial

Resource links provided by NLM:


Further study details as provided by Samsung Medical Center:

Primary Outcome Measures:
  • To evaluate the SBRT effect on local progression free survival rate [ Time Frame: Radiologic response will be evaluated at 3 month. ] [ Designated as safety issue: No ]
    Radiologic response will be evaluated at 1, 3 month after SBRT, and then every 3 month imaging follow up will be continued. Local progression will be defined by modified Modified response evaluation criteria for solid tumor (mRECIST). Local progression was defined as 20% or more size increase of contrast enhanced primary lesion or new contrast enhanced lesion in planning target volume.

  • To evaluate the SBRT effect on adverse events [ Time Frame: Adverse events will be evaluated at 3 month after SBRT. ] [ Designated as safety issue: No ]
    Adverse events will be evaluated at 1 and 3 month after SBRT, and then every 3 month follow up will be continued.. Adverse event will be evaluated with common terminology criteria for adverse events (CTCAE version 4.0) during follow up.


Secondary Outcome Measures:
  • To determine the SBRT objective response rate [ Time Frame: Response will be evaluated at 3 month ] [ Designated as safety issue: No ]
  • To measure the time to local tumor progression [ Time Frame: Response will be evaluated at 3 month after SBRT. ] [ Designated as safety issue: No ]
    Response will be evaluated at 3 month after SBRT, then every 3 month follow up with imaging will be continued. mRECIST will be used to define local tumor progression.

  • To measure the overall survival [ Time Frame: Survival will be evaluated at 3 month after SBRT. ] [ Designated as safety issue: No ]
    Survival will be evaluated at 3 month after SBRT, then every 3 month follow up will be continued. Overall survival will be measured from the data of SBRT start to the date of death or to the date of last follow up visit.

  • To measure the progression free survival [ Time Frame: Response will be evaluated at 3 month after SBRT. ] [ Designated as safety issue: No ]
    Response will be evaluated at 3 month after SBRT, then every 3 month follow up with imaging will be continued. mRECIST will be used to define response. Progression free survival will be measured from the date of SBRT to the date of progression recognition or to the date of lat follow up visit.


Other Outcome Measures:
  • Quality of life(QOL)change before and after RT [ Time Frame: QoL will be assessed before, and 1, 3, 6 months after SBRT. ] [ Designated as safety issue: No ]
    To measure the quality of life(QOL) before and after RT, European Organization for Research and Treatment of Cancer (EORTC) core Quality of Life Questionnaire (QLQ)-C30, Functional Assessment of Cancer Therapy-Hepatobiliary (FACT-Hep) will be used. Before simulation of RT, baseline QOL assessment will be obtained, then QOL will be assessed at 1, 3, 6 months after RT, before physician interview.

  • RT response prediction probability evaluation by diffusion-weighted (DW) MRI and PET [ Time Frame: At 1 month after RT ] [ Designated as safety issue: No ]

Estimated Enrollment: 60
Study Start Date: August 2013
Estimated Study Completion Date: June 2016
Estimated Primary Completion Date: June 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Stereotactic body radiotherapy
Stereotactic body radiotherapy 60 Gy/3 fraction standard dose The highest allowable dose with maintain normal tissue constraints
Radiation: Stereotactic body radiotherapy
Respiration training will be done on the day that patient decided participate this study with wearing video goggle and headphone assisted respiration by visual and voice. Four dimensional CT simulation with wearing video goggle and headphone assisted respiration by visual and voice and real time position management system (PRM) signal will be adopted. Planning MRI with diffusion image also be acquired in same condition with CT simulation. SBRT will be delivered daily 20 Gy for 3 fractions.

  Eligibility

Ages Eligible for Study:   20 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Patients must have a diagnosis of HCC by at least one criterion listed below (KLCSG guideline 2009) 1.1 Pathologically (histologically or cytologically) proven diagnosis of HCC 1.2 Liver nodule in high risk group 1.2.1 If alpha feto protein (AFP)≥200 ng/mL , ≥ 1 typical HCC enhancing pattern on dynamic contrast enhanced CT or MRI 1.2.2 If AFP<200 ng/mL, ≥2 typical HCC enhancing pattern on dynamic contrast enhanced CT, MRI, and angiography 1.3 ≥ 2 cm nodule in liver cirrhosis (LC), ≥ 1 typical HCC enhancing pattern on dynamic contrast enhanced CT or MRI
  2. Eastern cooperative oncology group performance status 0 or 1
  3. Size of the HCC ≤ 3 cm or less
  4. Age ≥ 20
  5. Unsuitable for resection or transplant or RFA
  6. Unsuitable for or refractory to TACE or drug eluting beads (DEB)
  7. Agreement of study-specific informed consent
  8. Assessment by radiation oncologist and medical oncologist or hepatologist within 28 days prior to study entry?
  9. Child-Pugh score A within 14 days prior to study entry
  10. normal liver (Liver minus gross tumor volume) ≥ 700 cc
  11. Target is only one viable hepatocellular carcinoma
  12. Blood work requirements

    • Absolute neutrophil count (ANC) ≥ 1,500 /mm3, Platelet ≥ 70,000/mm3, Hgb ≥ 8 g/dl
    • Liver function test (LFT): T. bilirubin<3.0 mg/dL, International normalized ratio (INR) < 1.7, Albumin ≥ 2.8g/dL, Aspartate aminotransferase (AST)/Alanine aminotransferase (ALT)< 6 X normal
    • Serum creatinine < 1.5 X normal, or Creatinine clearance rate ≥ 60 mL/min
  13. Male, consent contraception at least 6 months Childbearing potential woman, consent contraception at least 6 months
  14. Life expectancy more than 12 weeks
  15. Stable breathing more than 10 minutes
  16. Consent to fiducial marker insertion ( if needed )

Exclusion Criteria:

  1. Extrahepatic metastasis or malignant nodes
  2. Pregnant and/or breastfeeding woman
  3. Macroscopic vascular tumor involvement
  4. Previous upper abdominal RT history
  5. Uncontrolled active co-morbidity
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01910909

Contacts
Contact: Hee Chul Park, M.D., Ph.D. 82-2-3410-2612 hee.ro.park@samsung.com
Contact: Jeong Il Yu, M.D. 82-2-3410-2615 jeongil.yu@samsung.com

Locations
Korea, Republic of
Samsung Medical Center Recruiting
Seoul, Korea, Republic of, 135-710
Contact: Hee Chul Park, M.D., Ph.D.    82-2-3410-2612    hee.ro.park@samsung.com   
Principal Investigator: Hee Chul Park, M.D., Ph.D.         
Sponsors and Collaborators
Samsung Medical Center
Investigators
Principal Investigator: Hee Chul Park, M.D., Ph.D. Samsung Medical Center
  More Information

No publications provided

Responsible Party: Samsung Medical Center
ClinicalTrials.gov Identifier: NCT01910909     History of Changes
Other Study ID Numbers: 2013-06-005-001
Study First Received: July 17, 2013
Last Updated: January 13, 2014
Health Authority: South Korea: Institutional Review Board

Keywords provided by Samsung Medical Center:
Hepatocellular carcinoma
unresectable
small size
Stereotactic body radiotherapy

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Hepatocellular
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Adenocarcinoma
Liver Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Liver Diseases

ClinicalTrials.gov processed this record on August 19, 2014