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Completed

NCT Number: NCT01910909

Stereotactic Body Radiotherapy for Unresectable Hepatocellular Carcinoma

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.

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Key information

Conditions

Localized Non-Resectable Adult Hepatocellular Carcinoma Adenocarcinoma Carcinoma Carcinoma, Hepatocellular Digestive System Diseases Digestive System Neoplasms Liver Diseases Liver Neoplasms Neoplasms Neoplasms by Histologic Type Neoplasms by Site Neoplasms, Glandular and Epithelial

Age range

20 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Samsung Medical Center

Seoul, 135-710, South Korea

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • 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
  • Eastern cooperative oncology group performance status 0 or 1
  • Size of the HCC ≤ 3 cm or less
  • Age ≥ 20
  • Unsuitable for resection or transplant or RFA
  • Unsuitable for or refractory to TACE or drug eluting beads (DEB)
  • Agreement of study-specific informed consent
  • Assessment by radiation oncologist and medical oncologist or hepatologist within 28 days prior to study entry?
  • Child-Pugh score A within 14 days prior to study entry
  • normal liver (Liver minus gross tumor volume) ≥ 700 cc
  • Target is only one viable hepatocellular carcinoma
  • 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
  • Male, consent contraception at least 6 months Childbearing potential woman, consent contraception at least 6 months
  • Life expectancy more than 12 weeks
  • Stable breathing more than 10 minutes
  • Consent to fiducial marker insertion ( if needed )

Exclusion criteria

  • Extrahepatic metastasis or malignant nodes
  • Pregnant and/or breastfeeding woman
  • Macroscopic vascular tumor involvement
  • Previous upper abdominal RT history
  • Uncontrolled active co-morbidity

Treatment and study plan

stereotactic body radiotherapy

Radiation

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.

Primary outcomes

  1. To evaluate the SBRT effect on local progression free survival rate

    Time frame: Radiologic response will be evaluated at 3 month.

    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.

  2. To evaluate the SBRT effect on adverse events

    Time frame: Adverse events will be evaluated at 3 month after SBRT.

    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 outcomes

  1. To determine the SBRT objective response rate

    Time frame: Response will be evaluated at 3 month

  2. To measure the time to local tumor progression

    Time frame: Response will be evaluated at 3 month after SBRT.

    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.

  3. To measure the overall survival

    Time frame: Survival will be evaluated at 3 month after SBRT.

    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.

  4. To measure the progression free survival

    Time frame: Response will be evaluated at 3 month after SBRT.

    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 outcomes

  1. Quality of life(QOL)change before and after RT

    Time frame: QoL will be assessed before, and 1, 3, 6 months after SBRT.

    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.

  2. RT response prediction probability evaluation by diffusion-weighted (DW) MRI and positron emission tomography

    Time frame: At 1 month after RT

Sponsors and collaborators

Lead sponsor

Samsung Medical Center

Other

Registry information

Official study title

Effectiveness and Safety of the Stereotactic Body Radiation Therapy for Hepatocellular Carcinoma: Prospective Phase II Trial

Acronym: SBRT for HCC

Important dates

Study start
2013
Primary completion
2019
Study completion
2019
First posted
Jul 30, 2013
Registry last updated
Nov 22, 2023

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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