NCT02814461

The Safety and Maximum Tolerated Dose of Axitinib in Combination With Radiotherapy for HCC

A Phase I Clinical Trial Evaluating the Safety and Maximum Tolerated Dose of Axitinib in Combination With Radiotherapy for Advanced Hepatocellular Carcinoma (HCC)

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 9 (actual)
• Sponsor: Shin Kong Wu Ho-Su Memorial Hospital · Academic / Other
• Sex: All
• Age: 20 Years – 85 Years
• Healthy volunteers: Not accepted

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

Conditions

• Advanced Hepatocellular Carcinoma (HCC)

Interventions

Type	Name	Description
DRUG	Axitinib	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).
RADIATION	Radiation	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.)

Timeline

• Start date: 2015-11-01
• Primary completion: 2018-11-01
• Completion: 2018-11-01
• First posted: 2016-06-27
• Last updated: 2019-09-23

Locations

1 site across 1 country: Taiwan