This study will test the hypothesis that a novel combination of three drugs (sorafenib, sonidegib, and irinotecan), in conjunction with individually optimized doses, can be safely administered and lead to improved clinical outcomes in patients with hepatocellular carcinoma compared to standard of care. The main objective of this study is to establish safe dose ranges for the coadministration of sorafenib, sonidegib, and irinotecan in patients with hepatocellular carcinoma. Furthermore, we will collect data to inform the application of an artificial intelligence/computational approach to individual dosing of combination chemotherapy. Individualization of dosing will be achieved by using Phenotypic Personalized Medicine (PPM) to maximize treatment efficacy in patients with hepatocellular carcinoma, while minimizing toxicity. Drug efficacy will be assessed by measuring plasma circulating tumor DNA (ctDNA). Toxicity will be assessed by quantitating organ injury and patient tolerability. Recommended dosing for future studies will be based on the totality of the data.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
12
All subjects will be given either 25 mg/m2 (dose level -1), 50 mg/m2 (dose level 0), or 75 mg/m2 (dose level +1) irinotecan intravenously every 7 days.
All subjects will take 200 mg sonidegib orally either every 96 hours (dose level -1), every 48 hours (dose level 0), or every 24 hours (dose level +1).
All subjects will take 200 mg sorafenib orally either every 48 hours (dose level -1), every 24 hours (dose level 0), or every 12 hours (dose level +1).
University of Florida
Gainesville, Florida, United States
RECRUITINGMaximally tolerated dose
Determine the maximum tolerated dose of irinotecan, sonidegib, and sorafenib
Time frame: 32 days
Objective response rate
Determine the objective response rate, as measured by mRECIST 1.1 criteria
Time frame: 32 days
Change in the biomarker AFP
Measure the change in the blood level of the biomarker AFP
Time frame: 32 days
Change in the biomarker AFP-L3
Measure the change in the blood level of the biomarker AFP-L3
Time frame: 32 days
Change in the biomarker DGC
Measure the change in the blood level of the biomarker DGC
Time frame: 32 days
Change in the biomarker TGF-B
Measure the change in the blood level of the biomarker TGF-B
Time frame: 32 days
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