The Safety and Maximum Tolerated Dose of Axitinib in Combination With Radiotherapy for HCC
Condition: Advanced Hepatocellular Carcinoma (HCC)
MeSH terms: Carcinoma; Carcinoma, Hepatocellular
Study type: Interventional
Phase: Phase 1

Summary: 
      To determine the maximal tolerated dose (MTD) of axitinib in combination with RT for advanced
      HCC.
    

Detailed description: 
      The goal of this study is to conduct a phase I clinical trial evaluating the safety and MTD
      of axitinib in combination with RT for advanced HCC. There are some rationales of conducting
      this clinical trial. Firstly, there is evidence of benefit from the combination of a variety
      of anti-angiogenic agents with RT at the pre-clinical level. Numerous pre-clinical models
      have documented improved outcome with the combination of RT (e.g. bevacizumab ... etc).
      Potential increasing the oxygenation of tumors with anti-angiogenesis is also expected to
      improve the therapeutic ratio of radiation therapy to hypervascular caner like HCC. Secondly,
      spatial cooperation may exist between local treatment (e.g. RT) and systemic therapy (e.g.
      axitinib). From the experience of sorafenib, the majority of patients eventually progress
      within the liver and die of liver failure, providing rationale to use local therapies like
      RT. On the other hand, from the experience of RT, the most common site of first recurrence
      was in the liver outside the irradiated volume, providing rationale for studies combining
      regional or systemic therapies with RT. Thirdly, clinical experiences with RT and
      anti-angiogenic agent are few but still exist with encouraging results. For example, one
      retrospective review from Taiwan with advanced HCC treated with RT and sunitinib (a TKI with
      similar mechanisms as sorafenib) reported objective response rate of 74% and a median
      survival of 16 months, and concluded hypofractionated RT and sunitinib can be delivered
      safely in HCC patients, which was compatible with the result of several phase I or II studies
      using sorafenib plus. Fourthly, the safety and MTD of axitinib combined with RT is needed to
      be established before launch of a phase II study
    

Intervention name(s): Axitinib; Radiation
Intervention type(s): Drug; Radiation
Intervention description(s): Axitinib (dose escalation): for total 8 weeks during and after RT, with starting dose of 1mg BID. According to the rule of traditional 3 + 3 design, 3-level axitinib dose escalation will be conducted: 1mg BID (level - I), 2mg BID (level - II) and 3mg BID (level - III).; Radiotherapy (RT) dose (fixed strength for normal liver): 37.5 to 67.5 Gy in 15 fractions (2.5 to 4.5 Gy per fraction) to liver tumor(s) (e.g. portal vein thrombosis, tumors with size ≥3 cm, or recurrent/refractory tumors). The final prescribed dose is based on an upper limit of mean liver dose of 18 Gy for all plans. (Daily Entecavir 0.5-1mg or Telbivudine 600mg is recommended for patients with positive hepatitis B during and 3 months after RT.)
Other intervention name(s): Inlyta
Intervention MeSH terms: Axitinib
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment