Efficacy of Localized Concurrent Chemo-radiation Therapy and Sorafenib Sequential Therapy in Advanced Hepatocellular Carcinoma
Condition: Hepatocellular Carcinoma
MeSH terms: Carcinoma; Carcinoma, Hepatocellular
Study type: Interventional
Phase: Phase 2

Summary: 
      This is a single-center, single-arm, open-label, prospective phase 2 trial to assess the
      efficacy of localized concurrent chemoradiation therapy (CCRT) and sorafenib sequential
      therapy in subjects with advanced HCC. Approximately 47 subjects will be enrolled and will
      receive CCRT and sorafenib sequentially until all-cause mortality.
    

Detailed description: 
      This is a single-center, single-arm, open-label, prospective phase 2 trial to assess the
      efficacy of localized concurrent chemoradiation therapy (CCRT) and sorafenib sequential
      therapy in subjects with advanced HCC. Approximately 47 subjects will be enrolled and will
      receive CCRT and sorafenib sequentially until all-cause mortality.

      Sorafenib is the current standard of care for advanced hepatocellular carcinoma (HCC)
      patients following clinical results from the two pivotal trials in Western and Asian
      patients. The median overall survival in patients with unresectable hepatocellular carcinoma
      (HCC) who are treated with sorafenib have shown to be approximately 14 months. However in the
      presence of portal vein invasion or extrahepatic metastases, the median overall survival is
      significantly lowered to 5.6 - 8.9 months.

      Going forward, improvement in patient-related outcomes would be highly desirable.

      A pilot study has been conducted in subjects with advanced HCC with portal vein invasion for
      which effective therapeutic methods have not been established. This was a single-center,
      open-label study of localized concurrent chemoradiation therapy (CCRT) for locally advanced
      HCC patients with portal vein invasion. A total of 40 subjects with advanced HCC with portal
      vein invasion were enrolled. The subjects were treated with a total of 45 Gy of external beam
      radiotherapy (1.8 Gy per session, 5 sessions a week, for 5 weeks), with hepatic arterial
      infusion of 5-flourouracil (5-FU) during the first and last 5 days of radiation therapy (5-FU
      500 mg infusion for 5 hours) through the pre-inserted chemoport. Eighteen (45%) subjects had
      an objective tumor response at 1 month after completion of localized CCRT. The 3-year
      survival rate was 24.2% and median overall survival was 13.1 months.

      Treatment-related serious adverse events (CTCAE grade 3 or higher) were anemia, leukopenia,
      thrombocytopenia, mucositis and liver decompensation, and their rates were 2.5%, 2.4-5.0%,
      17.5%, 10% and 7.3-17.5%, respectively. In addition, 2.4-5.0% of adverse events were
      chemoport-related adverse events including infection and port obstruction.

      Although sorafenib has been shown to increase overall survival in advanced HCC patients as
      compared to placebo through anti-angiogenesis effect, its tumoricidal effect is not evident.
      Meanwhile, based on the above analysis from the pilot study, localized CCRT has been regarded
      as a promising treatment with tumoricidal effect for advanced HCC patients. Therefore,
      combining sorafenib treatment with CCRT is anticipated to augment anti-tumor effect and
      improve tumor response and median overall survival.
    

Intervention name(s): CCRT; sorafenib
Intervention type(s): Radiation; Drug
Intervention description(s): The subject is treated with a total of 45 Gy of external beam radiotherapy (1.8 Gy per session, 5 sessions a week, for 5 weeks), with hepatic arterial infusion of 5-flourouracil (5-FU) during the first and last 5 days of radiation therapy (5-FU 500 mg infusion for 5 hours) for radiosensitization through the pre-inserted chemoport.; Four weeks after completion of CCRT, the subject is given daily sorafenib treatment and will be followed for survival.
Other intervention name(s): Localized concurrent chemoradiation therapy(CCRT); sorafenib(Nexavar®) sequential therapy
Intervention MeSH terms: Sorafenib
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment