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

The recruitment status of this study is unknown because the information has not been verified recently.
Verified March 2011 by China Medical University Hospital.
Recruitment status was  Recruiting
Sponsor:
Information provided by:
China Medical University Hospital
ClinicalTrials.gov Identifier:
NCT01328223
First received: March 20, 2011
Last updated: April 1, 2011
Last verified: March 2011
  Purpose

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 Intervention Phase
Hepatocellular Carcinoma
Radiation: sorafenib and radiotherapy for hepatocellular carcinoma
Phase 2

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: Phase II Study of Combined Sorafenib With Radiotherapy in Patients With Advanced Hepatocellular Carcinoma

Resource links provided by NLM:


Further study details as provided by China Medical University Hospital:

Primary Outcome Measures:
  • Response rate [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
    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:
  • Disease progression-free survival [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]

    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.


  • Overall survival [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
    Participants will be followed. The average time period will be two years.


Estimated Enrollment: 45
Study Start Date: September 2010
Estimated Study Completion Date: December 2012
Estimated Primary Completion Date: June 2012 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
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.

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.

  Eligibility

Ages Eligible for Study:   20 Years to 69 Years
Genders Eligible for Study:   Both
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.

Criteria

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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01328223

Contacts
Contact: Shang-Wen Chen, MD 886-4-2205212 ext 7450 vincent1680616@yahoo.com.tw

Locations
Taiwan
Shang-Wen Chen Recruiting
Taichung, Taiwan, 404
Contact: Shang-Wen Chen, MD    886-4-22052121 ext 7450    vincent1680616@yahoo.com.tw   
Sub-Investigator: Yu-Cheng Kuo         
Sub-Investigator: Ji-An Liang, MD         
Li-Ching Lin Recruiting
Tainan, Taiwan, 700
Contact: Li-Ching Lin, MD       liching51@yahoo.com.tw   
Jeng-Fong Chiou Recruiting
Taipei, Taiwan, 100
Contact: Jeng-Fong Chiou, MD;PhD       sjfchiou@xuite.net   
Sponsors and Collaborators
China Medical University Hospital
Investigators
Principal Investigator: Shang-Wen Chen, MD Department of Radiation Oncology, China Medical University Hospital
  More Information

No publications provided

Responsible Party: Shang-Wen Chen, Department of Radiation Oncology
ClinicalTrials.gov Identifier: NCT01328223     History of Changes
Other Study ID Numbers: Radiotherapy-Sorafenib
Study First Received: March 20, 2011
Last Updated: April 1, 2011
Health Authority: Taiwan: Department of Health

Keywords provided by China Medical University Hospital:
Hepatocellular carcinoma
radiotherapy
sorafenib

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
Sorafenib
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on April 16, 2014