Combined Radiotherapy and Sorafenib in Patients With Hepatoma
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, we 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. The primary end points are response rate and toxicities
profile. The secondary endpoints are time to radiological progression interval (TRPI),
overall survival, and quality of life assessment.
Observational
Observational Model: Cohort, Time Perspective: Prospective
Response rate
Response rate at 1-month and 6-month after radiotherapy. Toxicities profile of combinede treatment
1-month and 6-month response rate
Yes
Shang-Wen Chen, MD
Principal Investigator
Department of Radiation Oncology, China Medical University Hospital
Taiwan: Department of Health
RT-sorafenib
NCT01319942
June 2010
June 2013
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