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

April 1, 2011 updated by: China Medical University Hospital

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

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.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

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

Enrollment (Anticipated)

45

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Taiwan
      • Taichung, Taiwan, 404
        • Recruiting
        • Shang-Wen Chen
        • Contact:
        • Sub-Investigator:
          • Yu-Cheng Kuo
        • Sub-Investigator:
          • Ji-An Liang, MD
      • Tainan, Taiwan, 700
      • Taipei, Taiwan, 100

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

20 years to 69 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

Paitents with unresectable hepatoma with transarterial chemoembolization (TACE) failure or who are not suitable for TACE.

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

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 Names:
  • Combined radiotherapy and sorafenib.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
6 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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 years
Overall survival
Time Frame: 2 years
Participants will be followed. The average time period will be two years.
2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

China Medical University Hospital

Investigators

  • Principal Investigator: Shang-Wen Chen, MD, Department of Radiation Oncology, China Medical University Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2010

Primary Completion (Anticipated)

June 1, 2012

Study Completion (Anticipated)

December 1, 2012

Study Registration Dates

First Submitted

March 20, 2011

First Submitted That Met QC Criteria

April 1, 2011

First Posted (Estimate)

April 4, 2011

Study Record Updates

Last Update Posted (Estimate)

April 4, 2011

Last Update Submitted That Met QC Criteria

April 1, 2011

Last Verified

March 1, 2011

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Radiotherapy-Sorafenib

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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