Phase II clinical trial of cabozantinib for the treatment of recurrent hepatocellular carcinoma after liver transplantation

Recurrent hepatocellular carcinoma (HCC) develops in 15-20% of liver transplant recipients, and it tends to be more aggressive due to underlying immunosuppression. The multikinase inhibitor cabozantinib has been shown to be effective for the treatment of advanced HCC. However, there is no study evaluating this medication in patients with recurrent HCC. Adult patients with measurable biopsy-proven recurrent HCC are eligible for enrollment provided they are not amenable to curative treatments and no prior treatment with cabozantinib. In this study, 60 mg once daily cabozantinib will be administered orally. Participants will receive study treatment as long as they continue to experience clinical benefit or until there is unacceptable toxicity. Tumor measurements will be repeated every 8 weeks to evaluate response. The primary end point of this study will be the disease control rate at 4 months after treatment. The secondary end points will be overall survival, progression-free survival and safety profile of cabozantinib. Furthermore, potential biomarkers will be evaluated to identify their role in tumor progression. The total duration of this trial is expected to be 3 years. We anticipate that this trial will show the effectiveness and safety of cabozantinib in the treatment of post-liver transplant recurrent HCC. Cabozantinib is expected to be an effective treatment due to its activity against many protein kinases, including MET and AXL which are not inhibited by sorafenib. Plain language summary: Liver cancer is the sixth most diagnosed cancer worldwide with few available curative treatments. Liver transplantation (LT) is considered as one of the treatments for liver cancer especially in earlier stages of cancer. However, after LT, cancer develops again in 15-20% of the patients who undergo transplant for liver cancer. Compared with liver cancer in the nontransplant population, recurrent cancer grows faster and spreads in the body very quickly. Therefore, unfortunately, to date there are limited treatment options for these patients without significant effect on their survival. In this study, we aim to evaluate the effect of a new medication called cabozantinib on patients who develop recurrent liver cancer after their LT. Cabozantinib has been already tested in patients with liver cancer and was shown to be effective and safe in nontransplant patients. However, this is the first study to evaluate the effect of cabozantinib in liver transplant recipients with recurrent liver cancer.