Clinical trial NCT01910909: Stereotactic Body Radiotherapy for Unresectable Hepatocellular Carcinoma
Official title: Effectiveness and Safety of the Stereotactic Body Radiation Therapy for Hepatocellular Carcinoma: Prospective Phase II Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Localized Non-Resectable Adult Hepatocellular Carcinoma
Keywords: Hepatocellular carcinoma
unresectable
small size
Stereotactic body radiotherapy
Lead sponsor: Samsung Medical Center
Sponsor class: OTHER
First posted: 2013-07-30
Enrollment: 56
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility 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

Primary outcomes:
measure: To evaluate the SBRT effect on local progression free survival rate
timeFrame: Radiologic response will be evaluated at 3 month.
measure: To evaluate the SBRT effect on adverse events
timeFrame: Adverse events will be evaluated at 3 month after SBRT.
Secondary outcomes:
measure: To determine the SBRT objective response rate
timeFrame: Response will be evaluated at 3 month
measure: To measure the time to local tumor progression
timeFrame: Response will be evaluated at 3 month after SBRT.
measure: To measure the overall survival
timeFrame: Survival will be evaluated at 3 month after SBRT.
measure: To measure the progression free survival
timeFrame: Response will be evaluated at 3 month after SBRT.
Other outcomes:
measure: Quality of life(QOL)change before and after RT
timeFrame: QoL will be assessed before, and 1, 3, 6 months after SBRT.
measure: RT response prediction probability evaluation by diffusion-weighted (DW) MRI and positron emission tomography
timeFrame: At 1 month after RT
Locations:
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
Study officials:
affiliation: Samsung Medical Center
name: Hee Chul Park, M.D., Ph.D.
role: PRINCIPAL_INVESTIGATOR
References: