Study of Combined Sorafenib With Radiotherapy in Patients With Advanced Hepatocellular Carcinoma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01328223
Recruitment Status : Unknown
Verified March 2011 by China Medical University Hospital.
Recruitment status was:  Recruiting
First Posted : April 4, 2011
Last Update Posted : April 4, 2011
Information provided by:
China Medical University Hospital

Brief Summary:

Hepatocellular carcinoma (HCC) is a common cause of cancer mortality in Asia. Most patients present with intermediate or advanced disease. Percutaneous ethanol injection, radiofrequency ablation, and transcatheter arterial chemoembolization (TACE) are not considered as a curative treatment and have achieved very limited success in eradicating large HCC. With the development of new radiotherapy (RT) technique, RT can be more safely given to patients with larger tumor burden. Thus, TACE combined with RT has been suggested for treating large HCC. Based on the results of these studies, RT could achieve a tumor response rate of 50 % to 70 %. However, it has not been definitively shown to prolong the overall or disease-free survival due to lack of a phase III clinical trial. In contrast, a retrospective clinical investigation with molecular study suggests that sublethal dose of RT promoted HCC growth outside RT field.

Two phase III trials were shown to be efficacious and well-tolerated in patients with advanced HCC. Median overall survival was significantly 2 to 3 months longer in the sorafenib group than that in the placebo. It is interesting to recognize the combined therapeutic effect of RT with sorafenib. Based on several preclinical experiments, tumor angiogenesis inhibitors seem to be synergistic with irradiation when using before RT, concurrently with RT, or after RT. Thus, the investigators design a single-arm phase II clinical trial to investigate the efficacy of combined RT with sorafenib.

The eligibility criteria are patients with unresectable HCC; good performance status; no prior radiotherapy for the liver; clinical measurable tumor; good liver function and good compliance. After entering this study, the testee will receive RT to hepatic tumor with concurrently sorafenib with a dose of 400 mg twice daily. Hepatic RT will be performed with a daily fraction size of 2.0 to 2.5 Gy to a total dose of 46 Gy to 60 Gy. After RT, maintenance sorafenib with a dose of 400 mg twice daily will be ongoing. Sorafenib will be continued until the occurrence of clinical or radiologic progression, or the occurrence of either unacceptable adverse events or death. Minimum maintenance duration of 6 months is recommended, but not mandatory.

Condition or disease Intervention/treatment
Hepatocellular Carcinoma Radiation: sorafenib and radiotherapy for hepatocellular carcinoma

Detailed Description:
The primary end points are response rate and toxicities profile. The secondary endpoints are time to disease-free survival, overall survival, and quality of life assessment.

Study Type : Observational
Estimated Enrollment : 45 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Phase II Study of Combined Sorafenib With Radiotherapy in Patients With Advanced Hepatocellular Carcinoma
Study Start Date : September 2010
Estimated Primary Completion Date : June 2012
Estimated Study Completion Date : December 2012

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Group/Cohort Intervention/treatment
radiotherapy efficacy
  1. Concurrent stage with RT: sorafenib 400mg twice daily
  2. Maintenance stage after RT: sorafenib 400mg twice daily Treatment can be continued until the occurrence of clinical or radiologic progression, the occurrence of either unacceptable adverse events, death, or any criteria met for removal from the protocol treatment. Basically, minimum maintenance duration of 6 months is recommended, not mandatory.
Radiation: sorafenib and radiotherapy for hepatocellular carcinoma
Concurrent and maintenance sorafenib 400mg twice daily
Other Name: Combined radiotherapy and sorafenib.

Primary Outcome Measures :
  1. Response rate [ Time Frame: 6 months ]
    1. The tumor response rate will be evaluated at the 6th month after the ending of radiotherapy.
    2. The response rate includes complete and partial response according to the RECIST (Response Evaluation Criteria in Solid Tumors) criteria.

Secondary Outcome Measures :
  1. Disease progression-free survival [ Time Frame: 2 years ]

    Disease progression-free survival:

    Patients with the evidence of clinical or radiographic progressive disease will be defined as disease progression. The average time period for the follow-up will be two years.

  2. Overall survival [ Time Frame: 2 years ]
    Participants will be followed. The average time period will be two years.

Information from the National Library of Medicine

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Ages Eligible for Study:   20 Years to 69 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Paitents with unresectable hepatoma with transarterial chemoembolization (TACE) failure or who are not suitable for TACE.

Inclusion Criteria:

  • Patients with unresectable hepatoma with transarterial embolization (TAE) failure or who are not suitable for TACE. A maximal tumor diameter > 3.0 cm.
  • Age: 20 ~ 69 years.
  • ECOG 0 or 1.
  • Life expectancy of at least 12 weeks.
  • Child-Pugh A or B (preferentially score ≦ 7).
  • Cancer of the Liver Italian Program (CLIP) score ≦ 3.
  • Pretreatment liver function test and renal function test:

    • Total bilirubin < 1.5 times the upper limit of normal (ULN)(≦ 3.0 (ULN) in patients treated by biliary drainage for obstructive jaundice)
    • GOP/GPT ≦ 5 X of upper limit of normal range
    • Alkaline phosphatase ≦ 4X of upper limit of normal range
    • Prothrombin time/partial prothrombin time < 1.5 X of ULN
    • Serum Creatinine ≦ 1.0 x ULN
  • Pretreatment blood count:

    • Hemoglobulin ≧ 9 g/dl
    • Absolute neutrophil count ≧ 1500/mm3
    • Platelet count ≧ 50,000/mm3
  • Subjects with at least one uni-dimensional or bi-dimensional measurable lesion. Lesion must be measured by CT scan or MRI.
  • Patients must fully recover from prior therapy that given > 4 weeks before enrollment.
  • Signed informed consent must be obtained prior to any study related procedures.

Exclusion Criteria:

  1. Child-Pugh C
  2. CLIP score ≧ 4
  3. Patients with evidence of extrahepatic or metastatic disease
  4. Patients with evidence of massive ascites
  5. Patients receiving previous irradiation to liver
  6. Patients with previous use of Thalidomide less than 6 months from entering of the study
  7. History of cardiac disease: congestive heart failure >NYHA class 2; active CAD (MI more than 6 mo prior to study entry is allowed); cardiac arrythmias requiring anti-arrythmic therapy (beta blockers or digoxin are permitted)
  8. Active clinically serious infections ( > grade 2 CTC version 2)
  9. Patients undergoing renal dialysis
  10. Patients with evidence or history of bleeding diathesis
  11. Prior treatment with EGFR TKIs or VEGFR TKIs
  12. Hypertension uncontrolled by medical therapy
  13. Symptomatic metastatic brain or meningeal tumors unless the patient is > 6 months from definitive therapy, has a negative imaging study within 4 weeks of study entry and is clinically stable with respect to the tumor at the time of study entry. Also the patient must not be undergoing acute steroid therapy or taper.
  14. Chemotherapy or immunotherapy or other systemic anti-cancer therapy within 4 weeks.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01328223

Contact: Shang-Wen Chen, MD 886-4-2205212 ext 7450

Shang-Wen Chen Recruiting
Taichung, Taiwan, 404
Contact: Shang-Wen Chen, MD    886-4-22052121 ext 7450   
Sub-Investigator: Yu-Cheng Kuo         
Sub-Investigator: Ji-An Liang, MD         
Li-Ching Lin Recruiting
Tainan, Taiwan, 700
Contact: Li-Ching Lin, MD   
Jeng-Fong Chiou Recruiting
Taipei, Taiwan, 100
Contact: Jeng-Fong Chiou, MD;PhD   
Sponsors and Collaborators
China Medical University Hospital
Principal Investigator: Shang-Wen Chen, MD Department of Radiation Oncology, China Medical University Hospital

Responsible Party: Shang-Wen Chen, Department of Radiation Oncology Identifier: NCT01328223     History of Changes
Other Study ID Numbers: Radiotherapy-Sorafenib
First Posted: April 4, 2011    Key Record Dates
Last Update Posted: April 4, 2011
Last Verified: March 2011

Keywords provided by China Medical University Hospital:
Hepatocellular carcinoma

Additional relevant MeSH terms:
Carcinoma, Hepatocellular
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Liver Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Liver Diseases
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Vitamin B Complex
Growth Substances
Physiological Effects of Drugs